Evaluation of the analytical performance of tests in medical laboratories is important. Total Error (TE) and sigma analysis have been used as a quantitative indicator of quality for many years. The aim of this study is to evaluate the analytical performance of Beckman Coulter Access Estradiol (E2) and Sensitive E2 reagents. Analytical performance of two reagents were evaluated with TE, six sigma and measurement uncertainty values. Two Beckman Coulter Unicel DxI-800 autoanalyzers (A1 and A2) included in the study. Quality control data between December 2017 and December 2019 were used. CLIA-2019 values were used for total allowable error (TEa) limits. Uncertainty values were calculated with ISO/TS 20914.
The median TE of the old generation and sensitive E2 reagent were 27.46% (between 13.49 and 48.88) and 11.16% (between 7.08 and 24.81), respectively (p < .005) The process sigma results were below 3 sigma in all months with the old reagent, whereas with the new reagents it was seen to be above 3 sigma in 11 of 12 months for both autoanalyzers. Uncertainty of old reagent is higher than new reagent. Imprecisions decrease as concentration increases with both reagents. The uncertainty values of low concentration levels are greater than high concentration levels. In conclusion, in both auto analyzers, Sensitive E2 reagent was found to have better performance than old reagent in terms of TE, process sigma and measurement uncertainty. We believe that the sensitive E2 reagent still needs further improvement for patients who have low E2 levels.
Prothymosin Alpha: A Novel Contributor to Estradiol Receptor Alpha-Mediated CD8 + T-Cell Pathogenic Responses and Recognition of Type 1 Collagen in Rheumatic Heart Valve Disease
Background: Rheumatic heart valve disease (RHVD) is a leading cause of cardiovascular death in low- and middle-income countries and affects predominantly women. The underlying mechanisms of chronic valvular damage remain unexplored and regulators of sex predisposition are unknown.
Methods: Proteomics analysis of human heart valves (nondiseased aortic valves, nondiseased mitral valves [NDMVs], valves from patients with rheumatic aortic valve disease, and valves from patients with rheumatic mitral valve disease; n=30) followed by system biology analysis identified ProTα (prothymosin alpha) as a protein associated with RHVD. Histology, multiparameter flow cytometry, and enzyme-linked immunosorbent assay confirmed the expression of ProTα. In vitro experiments using peripheral mononuclear cells and valvular interstitial cells were performed using multiparameter flow cytometry and quantitative polymerase chain reaction. In silico analysis of the RHVD and Streptococcus pyogenes proteomes were used to identify mimic epitopes.
Results: A comparison of NDMV and nondiseased aortic valve proteomes established the baseline differences between nondiseased aortic and mitral valves. Thirteen unique proteins were enriched in NDMVs. Comparison of NDMVs versus valves from patients with rheumatic mitral valve disease and nondiseased aortic valves versus valves from patients with rheumatic aortic valve disease identified 213 proteins enriched in rheumatic valves. The expression of the 13 NDMV-enriched proteins was evaluated across the 213 proteins enriched in diseased valves, resulting in the discovery of ProTα common to valves from patients with rheumatic mitral valve disease and valves from patients with rheumatic aortic valve disease. ProTα plasma levels were significantly higher in patients with RHVD than in healthy individuals. Immunoreactive ProTα colocalized with CD8+ T cells in RHVD. Expression of ProTα and estrogen receptor alpha correlated strongly in circulating CD8+ T cells from patients with RHVD. Recombinant ProTα induced expression of the lytic proteins perforin and granzyme B by CD8+ T cells as well as higher estrogen receptor alpha expression. In addition, recombinant ProTα increased human leukocyte antigen class I levels in valvular interstitial cells. Treatment of CD8+ T cells with specific estrogen receptor alpha antagonist reduced the cytotoxic potential promoted by ProTα. In silico analysis of RHVD and S pyogenes proteomes revealed molecular mimicry between human type 1 collagen epitope and bacterial collagen-like protein, which induced CD8+ T-cell activation in vitro.
Conclusions: ProTα-dependent CD8+ T-cell cytotoxicity was associated with estrogen receptor alpha activity, implicating ProTα as a potential regulator of sex predisposition in RHVD. ProTα facilitated recognition of type 1 collagen mimic epitopes by CD8+ T cells, suggesting mechanisms provoking autoimmunity.
Pharmacokinetic Interaction Between the MEK1/MEK2 Inhibitor Trametinib and Oral Contraceptives Containing Norethindrone and Ethinyl Estradiol in Female Patients With Solid Tumors
This phase 1 postapproval study assessed the effect of the mitogen-activated protein kinase kinase enzyme 1/enzyme 2 inhibitor trametinib (2 mg once daily, repeat dosing) on the pharmacokinetics of combined oral contraceptives (COCs) containing norethindrone (NE; 1 mg daily) and ethinyl estradiol (EE; 0.035 mg daily) in 19 female patients with solid tumors. Compared with NE/EE administered without trametinib, NE/EE administered with steady-state trametinib was associated with a clinically nonrelevant 20% increase in NE exposure (area under the curve [AUC]) and no effect on EE exposure (geometric mean ratio [geo-mean] of NE/EE + trametinib to NE/EE [90%CI]: NE AUC calculated to the end of a dosing interval at steady-state [AUCtau ] 1.20 [1.02-1.41]; NE AUC from time zero to the last measurable concentration sampling time [AUClast ] 1.2 [0.999-1.45]; EE AUCtau 1.06 [0.923-1.22]; EE AUClast 1.05 [0.883-1.25]).
Maximum serum concentration (Cmax ) of NE increased by 13% and Cmax of EE decreased by 8.5% when dosed with steady-state trametinib compared with COCs administered alone (geo-mean ratio [90%CI]: NE Cmax 1.13 [0.933-1.36]; EE Cmax 0.915 [0.803-1.04]). These results indicate that repeat-dose trametinib does not lower exposure to NE or EE and, hence, is unlikely to impact the contraceptive efficacy of COCs. The pharmacokinetic parameters of trametinib and its metabolite M5 were consistent with historic data of trametinib alone. Coadministration of trametinib and COCs was generally well tolerated in this study, with observed safety signals consistent with the known safety profile of trametinib and no new reported safety events. Overall, the findings indicate that hormonal COCs can be coadministered in female patients who receive trametinib monotherapy without compromising the contraceptive efficacy.
Estradiol 17b, 6-CMO (Estradiol 6, 17b CMO) |
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| MBS638945-5mg | MyBiosource | 5mg | 855 EUR |
Estradiol 17b, 6-CMO (Estradiol 6, 17b CMO) |
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| MBS638945-5x5mg | MyBiosource | 5x5mg | 3695 EUR |
Estradiol |
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| A8425-1000 | ApexBio | 1g | 42 EUR |
Estradiol |
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| A8425-5.1 | ApexBio | 10 mM (in 1mL DMSO) | 40 EUR |
Estradiol |
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| A8425-50 | ApexBio | 50 mg | 157.2 EUR |
Estradiol |
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| 317788 | MedKoo Biosciences | 500.0mg | 195 EUR |
Estradiol |
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| 20-abx185851 | Abbexa |
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Estradiol |
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| DE2693 | Demeditec Diagnostics | 96 | 84 EUR |
Estradiol |
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| E1KS1709 | EnoGene | 100 mg | 151.2 EUR |
Estradiol |
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| AT070 | Unibiotest | 1mg | 1641.6 EUR |
Estradiol |
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| AG070 | Unibiotest | 1 mg | 627.6 EUR |
Estradiol |
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| MBS122090-01mg | MyBiosource | 0.1mg | 220 EUR |
Estradiol |
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| MBS122090-1mg | MyBiosource | 1mg | 350 EUR |
Estradiol |
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| MBS122090-5x1mg | MyBiosource | 5x1mg | 1490 EUR |
Estradiol |
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| MBS122091-01mg | MyBiosource | 0.1mg | 220 EUR |
Estradiol |
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| MBS122091-1mg | MyBiosource | 1mg | 350 EUR |
Estradiol |
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| MBS122091-5x1mg | MyBiosource | 5x1mg | 1490 EUR |
Estradiol |
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| GP9683 | Glentham Life Sciences | 1g | 304.24 EUR |
Estradiol |
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| GWB-2E7E30 | GenWay Biotech | 1 ml | Ask for price |
Estradiol |
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| HY-B0141 | MedChemExpress | 500mg | 129.6 EUR |
Estradiol |
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| GP9683-1 | Glentham Life Sciences | 1 | 27.8 EUR |
Estradiol |
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| GP9683-10 | Glentham Life Sciences | 10 | 172.4 EUR |
Sucrose acetate isobutyrate (SAIB) as a delivery vehicle for estradiol and sulpiride: Evaluation of endocrine responses in geldings and ovarian response in seasonally anovulatory mares
Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic polymer, may be an alternative to VS. Four in vivo experiments assessed the efficacy of SAIB for delivery of sulpiride, estradiol cypionate (ECP), and estradiol benzoate (EB). The first three studies utilized geldings to compare prolactin and luteinizing hormone (LH) concentrations between sulpiride delivered in VS and SAIB, and ECP or EB delivered in SAIB. Sulpiride stimulated (P < .01) prolactin similarly between vehicles. Geldings pre-treated with EB had higher (P < .05) prolactin responses to sulpiride compared to ECP-treated geldings on days 5, 6 and 9.
Both estradiol-sulpiride treatments stimulated LH with no differences between ECP and EB. Experiment 3 compared a simultaneous injection of EB-sulpiride to a non-simultaneous injection (one day apart) of EB-sulpiride. Prolactin was stimulated (P < .05) in both treatment groups, but the response lasted 2 days longer in geldings treated a day apart. Plasma LH increased (P < .01) in both groups equally for 10 days. Experiment 4 applied simultaneous and non-simultaneous EB-sulpiride treatments to seasonally anovulatory mares to induce ovarian activity. Prolactin and LH were stimulated similarly between treatments; however, non-simultaneously treated mares tended (P = .07) to have an ovarian response earlier. In conclusion, SAIB was a suitable vehicle for administration of estradiol and sulpiride and could be an alternative to VS for sustained-release drug delivery.