scholarly journals Human Pro–B-Type Natriuretic Peptide Is Processed in the Circulation in a Rat Model

2011 ◽  
Vol 57 (6) ◽  
pp. 883-890 ◽  
Author(s):  
Alexander G Semenov ◽  
Karina R Seferian ◽  
Natalia N Tamm ◽  
Marina M Artem'eva ◽  
Alexander B Postnikov ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Natriuretic Peptide ◽  
Clearance Rate ◽  
Gel Filtration ◽  
High Plasma ◽  
Proteolytic Processing ◽  
Specific Time ◽  
Time Points ◽  
High Plasma Concentration ◽  
Terminal Half Life

BACKGROUND The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides. METHODS We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP. RESULTS ProBNP was effectively processed in the circulation into BNP (1–32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively. CONCLUSIONS In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.

Intoxication with Phenprocoumon (Marcoumar) Pharmacokinetics and Side Effects

1969 ◽  
Vol 21 (02) ◽  
pp. 320-324 ◽  
Author(s):  
K Seiler ◽  
F Duckert
Keyword(s):  
Plasma Concentration ◽  
Side Effects ◽  
Half Life ◽  
Plasma Proteins ◽  
Repeated Administration ◽  
High Plasma ◽  
Vitamin K1 ◽  
Clotting Factors ◽  
Therapeutic Concentration ◽  
High Plasma Concentration

SummaryA case of severe Marcoumar intoxication is described. Eleven hours after the intake a plasma concentration of 15.75 µg/ml was found which corresponds approximately to the 5-fold therapeutic concentration. Repeated administration of vitamin K1 made it possible to avoid extreme lowering of the activity of the clotting factors II, VII and X and to prevent bleeding. Side effects were not observed. The biologic half-life of Phenprocoumon has been found to be shortened at high plasma concentration (3.7 instead of 5.9 days). It is probable that in extreme concentration the drug is less strongly bound to the plasma proteins.

scholarly journals Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period, a Single-Center Observational Study

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 774
Author(s):  
Mara L. Leimanis-Laurens ◽  
Karen Ferguson ◽  
Emily Wolfrum ◽  
Brian Boville ◽  
Dominic Sanfilippo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Intensive Care ◽  
Critically Ill ◽  
Organ Dysfunction ◽  
Lipid Profiles ◽  
Critically Ill Children ◽  
P Value ◽  
Time Points ◽  
Logistic Organ Dysfunction ◽  
Multi Organ Dysfunction Syndrome

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.

Prognostic value of high plasma brain natriuretic peptide concentrations in very elderly persons

2003 ◽  
Vol 114 (4) ◽  
pp. 266-270 ◽  
Author(s):  
Ryuji Ueda ◽  
Masatoshi Yokouchi ◽  
Takaomi Suzuki ◽  
Eiichi Otomo ◽  
Takashi Katagiri
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Prognostic Value ◽  
High Plasma ◽  
Elderly Persons ◽  
Very Elderly ◽  
Plasma Brain Natriuretic Peptide

Biologic variability of N-terminal pro-brain natriuretic peptide in adult healthy cats

2016 ◽  
Vol 19 (2) ◽  
pp. 216-223 ◽  
Author(s):  
Autumn N Harris ◽  
Amara H Estrada ◽  
Alexander E Gallagher ◽  
Brandy Winter ◽  
Kenneth E Lamb ◽  
...  
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cardiac Disease ◽  
Complete Blood Count ◽  
Individual Variability ◽  
P Value ◽  
Time Points ◽  
Total Thyroxine ◽  
Index Of Individuality ◽  
Adult Cats

Objectives The biologic variability of N-terminal pro-brain natriuretic peptide (NT-proBNP) and its impact on diagnostic utility is unknown in healthy cats and those with cardiac disease. The purpose of this study was to determine the biologic variation of NT-proBNP within-day and week-to-week in healthy adult cats. Methods Adult cats were prospectively evaluated by complete blood count (CBC), biochemistry, total thyroxine, echocardiography, electrocardiography and blood pressure, to exclude underlying systemic or cardiac disease. Adult healthy cats were enrolled and blood samples were obtained at 11 time points over a 6 week period (0, 2 h, 4 h, 6 h, 8 h, 10 h and at weeks 2, 3, 4, 5 and 6). The intra-individual (coefficient of variation [CVI]) biologic variation along with index of individuality and reference change values (RCVs) were calculated. Univariate models were analyzed and included comparison of the six different time points for both daily and weekly samples. This was followed by a Tukey’s post-hoc adjustment, with a P value of <0.05 being significant. Results The median daily and weekly CVI for the population were 13.1% (range 0–28.7%) and 21.2% (range 3.9–68.1%), respectively. The index of individuality was 0.99 and 1 for daily and weekly samples, respectively. The median daily and weekly RCVs for the population were 39.8% (range 17.0–80.5%) and 60.5% (range 20.1–187.8%), respectively. Conclusions and relevance This study demonstrates high individual variability for NT-proBNP concentrations in a population of adult healthy cats. Further research is warranted to evaluate NT-proBNP variability, particularly how serial measurements of NT-proBNP may be used in the diagnosis and management of cats with cardiac disease.

Analysis of minimal residual disease in bone marrow by NGF and in peripheral blood by mass spectrometry in newly diagnosed multiple myeloma patients enrolled in the GEM2012MENOS65 clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8010-8010
Author(s):  
Noemi Puig ◽  
Bruno Paiva ◽  
Teresa Contreras ◽  
M. Teresa Cedena ◽  
Laura Rosiñol ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Prognostic Value ◽  
Residual Disease ◽  
Newly Diagnosed ◽  
Time Points ◽  
Minimal Residual

8010 Background: Analysis of minimal residual disease (MRD) in the bone marrow (BM) of patients with multiple myeloma (MM) is accepted by the IMWG to evaluate treatment efficacy and is a well-established prognostic factor. However, there is an unmet need to explore the clinical value of MRD in peripheral blood (PB). Methods: Newly diagnosed MM patients enrolled in the GEM2012MENOS65 trial received six induction (Ind) cycles of bortezomib, lenalidomide, and dexamethasone (VRD) followed by autologous stem cell transplantation (ASCT) and 2 further cycles of consolidation (Cons) with VRD. MRD was analyzed in BM using Next Generation Flow (NGF) and in serum by Mass Spectrometry (MS) using IgG/A/M, κ, λ, free κ and free λ specific beads, both after Ind, at day 100 after ASCT, and after Cons. Sequential samples from the first 184 patients were analyzed. Results: Results of both methods were in agreement (NGF+/MS+ and NGF-/MS-) in 83% of cases post-Ind (152/184), 80% post-ASCT (139/174) and 76% post-Cons (128/169). Stratifying by the log range of MRD by NGF, discordances (NGF+/MS- and NGF-/MS+) seemed to increase at the lower MRD ranges, being 22%, 21% and 19% from ≥10−5 to <10−4 and 21%, 21%, 23% at ≥x10−6(post-Ind, ASCT and Cons, respectively). Analysis of discordances showed that they could be partly explained by the higher percentages of cases found to be positive by MS as compared by NGF at part of the time-points analyzed and at each log range of MRD. From ≥10−5 to <10−4, MRD was detected by NGF in 36%, 28%, 20% of cases post-Ind, ASCT and Cons, respectively vs MS in 37%, 29%, 21% of them; at ≥x10−6, NGF was positive in 11%, 14%, 19% of cases vs MS in 23%, 19% and 16% of them. Considering NGF as a reference, the negative predictive value (NPV) of MS per MRD range (≥10−5 to <10−4 and ≥x10−6, respectively) was: post-Ind: 83% (p<0,0001), 94% (p=0,034); post-ASCT 86% (p<0,0001), 90% (p=0,022); post-Cons 89% (p<0,0001), 85% (p=0,0469). Despite these discordances, the prognostic value of each technique in terms of undetectable MRD and progression-free survival (PFS) was consistent at all time-points (Table) and further, discordant cases (NGF+/MS- and NGF-/MS+) did not display a significantly different PFS as compared to NGF-/MS- cases. Conclusions: The results of MRD assessed by NGF in BM and by MS in PB show a significant concordance and are associated with a similar prognostic value analyzed in terms of PFS. Given its high NPV, MRD in peripheral blood by MS provides a gateway for BM aspiration/biopsy and MRD assessment by NGF.[Table: see text]

scholarly journals rhEPO (recombinant human eosinophil peroxidase): expression in Pichia pastoris and biochemical characterization

2006 ◽  
Vol 395 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Chiara Ciaccio ◽  
Alessandra Gambacurta ◽  
Giampiero DE Sanctis ◽  
Domenico Spagnolo ◽  
Christina Sakarikou ◽  
...  
Keyword(s):  
Pichia Pastoris ◽  
Biochemical Characterization ◽  
Expression System ◽  
Gel Filtration ◽  
Proteolytic Processing ◽  
Kinetic Properties ◽  
Specific Substrate ◽  
Human Eosinophil ◽  
Eosinophil Peroxidase ◽  
Pichia Pastoris Expression System

A Pichia pastoris expression system has for the first time been successfully developed to produce rhEPO (recombinant human eosinophil peroxidase). The full-length rhEPO coding sequence was cloned into the pPIC9 vector in frame with the yeast α-Factor secretion signal under the transcriptional control of the AOX (acyl-CoA oxidase) promoter, and transformed into P. pastoris strain GS115. Evidence for the production of rhEPO by P. pastoris as a glycosylated dimer precursor of approx. 80 kDa was determined by SDS/PAGE and gel filtration chromatography. Recombinant hEPO undergoes proteolytic processing, similar to that in the native host, to generate two chains of approx. 50 and 20 kDa. A preliminary biochemical characterization of purified rhEPO demonstrated that the spectral and kinetic properties of the recombinant wild-type EPO are comparable with those of the native enzyme and are accompanied by oxidizing activity towards several physiological anionic substrates such as SCN−, Br− and Cl−. On the basis of the estimated Km and kcat values it is evident that the pseudohalide SCN− is the most specific substrate for rhEPO, consistent with the catalytic properties of other mammalian EPOs purified from blood.

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