scholarly journals Blood Plasma Quality Control by Plasma Glutathione Status

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 864
Author(s):  
Tamara Tomin ◽  
Natalie Bordag ◽  
Elmar Zügner ◽  
Abdullah Al-Baghdadi ◽  
Maximilian Schinagl ◽  
...  
Keyword(s):  
Quality Control ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Linear Increase ◽  
Clinical Parameters ◽  
Clinical Environment ◽  
Lactate Dehydrogenase Activity ◽  
Glutathione Status ◽  
Potential Marker ◽  
Downstream Analysis

Timely centrifugation of blood for plasma preparation is a key step to ensure high plasma quality for analytics. Delays during preparation can significantly influence readouts of key clinical parameters. However, in a routine clinical environment, a strictly controlled timeline is often not feasible. The next best approach is to control for sample preparation delays by a marker that provides a readout of the time-dependent degradation of the sample. In this study, we explored the usefulness of glutathione status as potential marker of plasma preparation delay. As the concentration of glutathione in erythrocytes is at least two orders of magnitude higher than in plasma, even the slightest leakage of glutathione from the cells can be readily observed. Over the 3 h observation period employed in this study, we observed a linear increase of plasma concentrations of both reduced (GSH) and oxidized glutathione (GSSG). Artificial oxidation of GSH is prevented by rapid alkylation with N-ethylmaleimide directly in the blood sampling vessel as recently published. The observed relative leakage of GSH was significantly higher than that of GSSG. A direct comparison with plasma lactate dehydrogenase activity, a widely employed hemolysis marker, clearly demonstrated the superiority of our approach for quality control. Moreover, we show that the addition of the thiol alkylating reagent NEM directly to the blood tubes does not influence downstream analysis of other clinical parameters. In conclusion, we report that GSH gives an excellent readout of the duration of plasma preparation and the associated pre-analytical errors.

scholarly journals Plasma glutathione status as indicator of pre-analytical centrifugation delay

2020 ◽  
Author(s):  
Tomin Tamara ◽  
Natalie Bordag ◽  
Elmar Zuegner ◽  
Abdullah Al-Baghdadi ◽  
Maximilian Schinagl ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Time Dependent ◽  
Dependent Manner ◽  
Prolonged Incubation ◽  
Glutathione Status ◽  
Potential Marker ◽  
Analytical Centrifugation ◽  
Plasma Glutathione ◽  
Downstream Analysis

Prolonged incubation of blood prior to plasma preparation can significantly influence the quality of the resulting data. Different markers for this pre-clinical variability have been proposed over the years but with limited success. In this study we explored the usefulness of glutathione (GSH) status, namely ratio of reduced to oxidized glutathione (GSH/GSSG), as potential marker of plasma preparation delay. For that purpose, blood from 20 healthy volunteers was collected into tubes with a cysteine quencher (N-ethylmaleimide; NEM) for GSH stabilization. Plasma preparation was delayed at room temperature for up to 3 hours and every hour, a plasma sample was prepared and the GSH/GSSG ratio measured. We report that over the course of the investigation, plasma concentrations of both GSH and GSSG increased linearly (R2 = 0.99 and 0.98, respectively). Since GSH increased at a much faster rate compared to GSSG, the GSH/GSSG ratio also increased linearly in a time dependent manner (R2 = 0.99). As GSH is an intracellular antioxidant, we speculated that this might stem from ongoing blood hemolysis, which was confirmed by the time dependent rise in lactate dehydrogenase (LDH) activity in the plasma samples. Moreover, we demonstrate that the addition of the thiol alkylating reagent NEM directly to the blood tubes does not seem to influence downstream analysis of clinical parameters. In conclusion we propose that the glutathione status could be used as an indicator of the centrifugation delay prior to plasma preparation.

Circulating and muscle glutathione turnover in human endotoxaemia

2009 ◽  
Vol 117 (9) ◽  
pp. 313-319 ◽  
Author(s):  
Urban B. Fläring ◽  
Christina Hebert ◽  
Jan Wernerman ◽  
Folke Hammarqvist ◽  
Olav E. Rooyackers
Keyword(s):  
Skeletal Muscle ◽  
Healthy Volunteers ◽  
Whole Blood ◽  
Initial Phase ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Synthesis Rate ◽  
Total Glutathione ◽  
Endotoxin Challenge ◽  
Glutathione Status

Patients with septic shock have high plasma glutathione concentrations, whereas intracellular concentrations in erythrocytes and muscle are low. In the present study, we investigated the temporal pattern of glutathione status and glutathione kinetics in healthy volunteers during the initial phase of sepsis using a human endotoxin model. The present study was a descriptive pilot study in healthy male volunteers (n=8) before and after an endotoxin challenge. The glutathione status was determined in plasma and whole blood at baseline and hourly for 4 h after intravenous endotoxin injection and in skeletal muscle at baseline and at 2 and 4 h after endotoxin injection. In plasma, the concentration of total glutathione decreased 24% (P<0.05) at 3 h after endotoxin injection and 32% (P<0.001) at 4 h. In whole blood and skeletal muscle, the concentrations of both GSH and total glutathione as well as the redox status remained unaltered during the initial 4 h after the endotoxin challenge. The FSR (fractional synthesis rate) of glutathione in whole blood was 38±20%/day before and 59±22%/day 4 h after the endotoxin challenge (P=0.088) and in skeletal muscle this was 41±25 and 46±18%/day (P=0.68) respectively. During the initial phase of sepsis, as represented by an intravenous endotoxin challenge to healthy volunteers, plasma concentrations of total glutathione decreased, whereas glutathione status and synthesis rate in skeletal muscle and whole blood remained unaltered. However, due to the variation in the synthesis measurements, larger studies are needed to confirm these findings.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Morgan R. Peltier ◽  
Michael J. Fassett ◽  
Yuko Arita ◽  
Vicki Y. Chiu ◽  
Jiaxiao M. Shi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Los Angeles ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Plasma Concentrations ◽  
First Trimester ◽  
High Plasma ◽  
Thyroid Stimulating Hormone ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

Abstract Objectives Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. Methods Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. Results We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. Conclusions These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

scholarly journals Validation of an HPLC–MS/MS Method for the Determination of Plasma Ticagrelor and Its Active Metabolite Useful for Research and Clinical Practice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 278
Author(s):  
Jennifer Lagoutte-Renosi ◽  
Bernard Royer ◽  
Vahideh Rabani ◽  
Siamak Davani
Keyword(s):  
Active Metabolite ◽  
Plasma Concentrations ◽  
Antiplatelet Agent ◽  
High Plasma ◽  
Therapeutic Drug ◽  
Routine Practice ◽  
Daily Routine ◽  
Limit Of Quantification ◽  
Wide Range

Ticagrelor is an antiplatelet agent which is extensively metabolized in an active metabolite: AR-C124910XX. Ticagrelor antagonizes P2Y12 receptors, but recently, this effect on the central nervous system has been linked to the development of dyspnea. Ticagrelor-related dyspnea has been linked to persistently high plasma concentrations of ticagrelor. Therefore, there is a need to develop a simple, rapid, and sensitive method for simultaneous determination of ticagrelor and its active metabolite in human plasma to further investigate the link between concentrations of ticagrelor, its active metabolite, and side effects in routine practice. We present here a new method of quantifying both molecules, suitable for routine practice, validated according to the latest Food and Drug Administration (FDA) guidelines, with a good accuracy and precision (<15% respectively), except for the lower limit of quantification (<20%). We further describe its successful application to plasma samples for a population pharmacokinetics study. The simplicity and rapidity, the wide range of the calibration curve (2–5000 µg/L for ticagrelor and its metabolite), and high throughput make a broad spectrum of applications possible for our method, which can easily be implemented for research, or in daily routine practice such as therapeutic drug monitoring to prevent overdosage and occurrence of adverse events in patients.

scholarly journals Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2723
Author(s):  
Yu-Ping Yang ◽  
Teresa M. Giret ◽  
Richard J. Cote
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ex Vivo ◽  
Detection Sensitivity ◽  
Clinical Utilization ◽  
Diagnosis And Prognosis ◽  
Early Cancer Diagnosis ◽  
Potential Marker ◽  
Potential Applications ◽  
Downstream Analysis

Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their associated cells (e.g., immune cells and stromal cells) in the circulation. In this review, we briefly summarize existing CTC isolation technologies and specifically focus on advances in downstream analysis of CTCs and their potential applications in precision medicine. We also discuss the current challenges and future opportunities in their clinical utilization.

Propranolol in Children: Safety-Toxicity

PEDIATRICS ◽  
1982 ◽  
Vol 70 (1) ◽  
pp. 30-31
Author(s):  
Michael Artman ◽  
Mitch Grayson ◽  
Robert C. Boerth
Keyword(s):  
Heart Rate Response ◽  
Plasma Concentrations ◽  
Caloric Intake ◽  
High Plasma ◽  
Intravenous Glucose ◽  
First Case ◽  
Acute Ingestion ◽  
Pharmacologic Effect ◽  
Propranolol Therapy ◽  
Very High

Four hours after acute ingestion of 400 to 1,200 mg of propranolol by a healthy, 3-year-old boy, his plasma concentration of propranolol was 2,289 ng/ml. The only pharmacologic effect observed was a diminished heart rate response to crying and activity. In a second case, a 4-year-old boy on chronic propranolol therapy for renovascular hypertension had a hypoglycemic seizure when solid food was refused for three days because of an oral wound. The hypoglycemia was easily managed with intravenous glucose, and there were no sequelae. The first case alludes to the safety of propranolol in a healthy child even with very high plasma concentrations. The second case suggests the necessity of anticipating and avoiding hypoglycemia that can develop in children on chronic propranolol therapy when caloric intake is impaired.

Isavuconazole: Case Report and Pharmacokinetic Considerations

Chemotherapy ◽  
2018 ◽  
Vol 63 (5) ◽  
pp. 253-256 ◽  
Author(s):  
Francesco Marchesi ◽  
Corrado Girmenia ◽  
Bianca Maria Goffredo ◽  
Emanuela Salvatorelli ◽  
Atelda Romano ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Real Life ◽  
Concomitant Administration ◽  
Invasive Fungal Disease ◽  
High Plasma ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Hepatic Toxicity ◽  
Maintenance Chemotherapy

Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a “probable” IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.

PROLONGED RELEASE BY DIOESTROUS RATS OF FOLLICLE-STIMULATING HORMONE DURING THE PERIOD OF OVULATION INDUCED BY LUTEINIZING HORMONE RELEASING HORMONE

1979 ◽  
Vol 81 (1) ◽  
pp. 109-118 ◽  
Author(s):  
SHUJI SASAMOTO ◽  
SHIGEO HARADA ◽  
KAZUYOSHI TAYA
Keyword(s):  
Luteinizing Hormone ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Oestrous Cycle ◽  
Prolonged Release ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Follicular Maturation ◽  
Lh Rh ◽  
Premature Ovulation

When 1·0 μg luteinizing hormone releasing hormone (LH-RH) was given i.v. three times at 1 h intervals from 17.00 to 19.00 h on the day of dioestrus (day 0) to regular 4 day cyclic rats, premature ovulation was induced the next morning (day 1) with the number of ova present comparable to normal spontaneous ovulation. The next spontaneous ovulation occurred on the morning of day 5, 4 days after premature ovulation induced by LH-RH. Plasma concentrations of FSH and LH showed transient rises and falls within 1 h of administration of LH-RH; concentrations of FSH in the plasma decreased from 20.00 h on day 0 but markedly increased again from 23.00 h on day 0 to 02.00 h on day 1 and these high levels persisted until 14.00 h on day 1, with only a small increase of plasma LH during this period. The duration of increased FSH release during premature ovulation induced by LH-RH treatment was 6 h longer than the FSH surge occurring after administration of HCG on day 0. Surges of gonadotrophin were absent on the afternoon of day 1 (the expected day of pro-oestrus) and the surges characteristic of pro-oestrus occurred on the afternoon of day 4 and ovulation followed the next morning. The pituitary content of FSH did not decrease despite persisting high plasma levels of FSH during premature ovulation induced by either LH-RH or HCG on day 0. The changes in uterine weight indicated that the pattern of oestrogen secretion from the day of premature ovulation induced by LH-RH to the day of the next spontaneous ovulation was similar to that of the normal 4 day oestrous cycle. When 10 i.u. HCG were given on day 0, an increase in oestrogen secretion occurred on day 2, 1 day earlier than in the group given LH-RH on day 0. This advancement of oestrogen secretion was assumed to be responsible for the gonadotrophin surges on day 3. Similar numbers of fully developed follicles were found by 17.00 h on day 2 after premature ovulation induced by either LH-RH or HCG, suggesting that the shorter surge of FSH during premature ovulation induced by HCG had no serious consequences on the initiation of follicular maturation for the succeeding oestrous cycle in these rats. Administration of LH-RH on day 0 had no direct effect on the FSH surge during premature ovulation. Secretory changes in the ovary during ovulation may be responsible for this prolonged selective release of FSH.

Influence of High Plasma Concentrations of Free Fatty Acids on Heart Rhythm in Healthy Fasting Men

2009 ◽  
Vol 205 (1-6) ◽  
pp. 299-301 ◽  
Author(s):  
Harald Wang ◽  
Knut Rasmussen ◽  
Harald Vik-Mo ◽  
Ole D. Mjøs ◽  
Helge Grendahl
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Plasma Concentrations ◽  
Heart Rhythm ◽  
High Plasma

scholarly journals Inflammatory Biomarker Score Identifies Patients with Six-Fold Increased Risk of One-Year Mortality after Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4599
Author(s):  
Alisa D. Kjaergaard ◽  
Inna M. Chen ◽  
Astrid Z. Johansen ◽  
Børge G. Nordestgaard ◽  
Stig E. Bojesen ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
High Plasma ◽  
Carbohydrate Antigen ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Inflammatory Biomarker ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Increased Risk ◽  
One Year

We examined whether elevated plasma C-reactive protein (CRP), carbohydrate antigen (CA) 19-9, interleukin-6 (IL-6) and YKL-40, individually or combined, can identify poor survivors among patients with pancreatic ductal adenocarcinoma (PDAC). We measured CRP, CA 19-9, IL-6 and YKL-40 in 993 patients at the time of PDAC diagnosis. The biomarker score was the sum of biomarker categories, coded 0, 1 and 2 for low, intermediate and high plasma concentrations, respectively. High vs. low levels of CRP, CA 19-9 and IL-6 were each independently associated with a two-fold increased risk of one-year mortality. CRP performed best in patients with advanced and CA 19-9 in patients with low cancer stages. YKL-40 was not associated with mortality and, therefore, was not included in the biomarker score. Compared to the biomarker score = 0, the multifactorially adjusted hazard ratios for one-year mortality were 1.56 (95% confidence interval: 0.99–2.44) for score = 1, 2.22 (1.41–3.49) for score = 2, 3.44 (2.20–5.38) for score = 3, 5.13 (3.21–8.17) for score = 4 and 6.32 (3.84–10.41) for score = 5–6 (p-value for trend = 3 × 10−31). This score performed better than any single biomarker or combination of biomarkers when examined in similarly sized or other categories. In conclusion, a combination score of elevated CRP, CA 19-9 and IL-6 identified patients with six-fold higher one-year mortality.

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