Biochemical Assessment and Clinical Evaluation of a Non-Ionic Adsorbent Resin in Patients with Intractable Jaundice

2000 ◽  
Vol 23 (5) ◽  
pp. 312-318 ◽  
Author(s):  
P. Pazzi ◽  
R. Scagliarini ◽  
A.C. Puviani ◽  
G. Lodi ◽  
E. Morsiani ◽  
...  
Keyword(s):  
Bile Acids ◽  
Human Plasma ◽  
Serum Bile Acid ◽  
Liver Support ◽  
Artificial Liver Support ◽  
Healthy Donors ◽  
Severe Jaundice ◽  
Biochemical Assessment

We investigated in vitro and in vivo the ability of a non-ionic adsorbing resin (styrenedivinylbenzene copolymer) to remove bilirubin and bile acids from human plasma. In preliminary experiments, human plasma from healthy donors, enriched in conjugated bile acids and bilirubin, and pooled plasma from jaundiced patients were recirculated through the resin column. The removal of bilirubin and bile acids was evaluated at two different flow rates (200 ml/min and 40 ml/min), and compared to an activated charcoal column. Four patients with severe jaundice were subsequently treated by 4-hour plasmaperfusion through the resin. The in vitro studies showed that after 1 hour the removal of bile acids was almost complete and bilirubin level decreased significantly, reaching a plateau after 4 hours. In the in vivo study, all treatments were well tolerated. After plasmaperfusion, serum bile acid levels decreased by 64.9–94.6% and total bilirubin by 35.3–57.7%. No clinical or biochemical side effects were observed. Our data suggest that plasmaperfusion through this resin is safe and efficient for removal of bilirubin and bile acids in jaundiced patients. Thus, it may serve as a method of artificial liver support in the treatment of cholestatic syndromes.

Potentially Thrombogenic Materials in Factor IX Concentrates

1975 ◽  
Vol 33 (03) ◽  
pp. 617-631 ◽  
Author(s):  
H. S Kingdon ◽  
R. L Lundblad ◽  
J. J Veltkamp ◽  
D. L Aronson
Keyword(s):  
Human Plasma ◽  
Antithrombin Iii ◽  
Factor Ix ◽  
In Vitro Assays ◽  
Substantial Agreement ◽  
Coefficient Of Correlation

SummaryFactor IX concentrates manufactured from human plasma and intended for therapeutic infusion in man have been suspected for some time of being potentially thrombogenic. In the current studies, assays were carried out in vitro and in vivo for potentially thrombogenic materials. It was possible to rank the various materials tested according to the amount of thrombogenic material detected. For concentrates not containing heparin, there was substantial agreement between the in vivo and in vitro assays, with a coefficient of correlation of 0.77. There was no correlation between the assays for thrombogenicity and the antithrombin III content. We conclude that many presently available concentrates of Factor IX contain substantial amounts of potentially thrombogenic enzymes, and that this fact must be considered in arriving at the decision whether or not to use them therapeutically.

Presence and Possible Origin of ɛ(γ-Glutamyl)Lysine Isodipeptide in Human Plasma

1992 ◽  
Vol 67 (01) ◽  
pp. 060-062 ◽  
Author(s):  
J Harsfalvi ◽  
E Tarcsa ◽  
M Udvardy ◽  
G Zajka ◽  
T Szarvas ◽  
...  
Keyword(s):  
Human Plasma ◽  
Fibrinolytic Therapy ◽  
Normal Human Plasma ◽  
Normal Human ◽  
Hplc Technique ◽  
Significant Change

Summaryɛ(γ-glutamyl)lysine isodipeptide has been detected in normal human plasma by a sensitive HPLC technique in a concentration of 1.9-3.6 μmol/1. Incubation of in vitro clotted plasma at 37° C for 12 h resulted in an increased amount of isodipeptide, and there was no further significant change when streptokinase was also present. Increased in vivo isodipeptide concentrations were also observed in hypercoagulable states and during fibrinolytic therapy.

scholarly journals T cell mediated hypersensitivity to previously tolerated iodinated contrast media precipitated by introduction of atezolizumab

2021 ◽  
Vol 9 (5) ◽  
pp. e002521
Author(s):  
Sean Hammond ◽  
Anna Olsson-Brown ◽  
Joshua Gardner ◽  
Paul Thomson ◽  
Serat-E Ali ◽  
...  
Keyword(s):  
Contrast Media ◽  
Adverse Reactions ◽  
Stevens Johnson Syndrome ◽  
Iodinated Contrast ◽  
Immune Mediated ◽  
Johnson Syndrome ◽  
Healthy Donors ◽  
Concomitant Medications

Many adverse reactions associated with immune checkpoint inhibitor (ICI) treatments are immunologically driven and may necessitate discontinuation of the ICI. Herein, we present a patient who had been administered the radio contrast media amidotrizoate multiple times without issue but who then developed a Stevens-Johnson syndrome reaction after coadministration of atezolizumab. Causality was confirmed by a positive re-challenge with amidotrizoate and laboratory investigations that implicated T cells. Importantly, the introduction of atezolizumab appears to have altered the immunologic response to amidotrizoate in terms of the tolerance–elicitation continuum. Proof of concept studies demonstrated enhancement of recall responses to a surrogate antigen panel following in-vitro (healthy donors) and in-vivo (ICI patients) administrations of ICIs. Our findings highlight the importance of considering all concomitant medications in patients on ICIs who develop immune-mediated adverse reactions. In the event of some immune-related adverse reactions, it may be critical to identify the culprit antigen-forming entity that the ICIs have altered the perception of rather than simply attribute causality to the ICI itself in order to optimize both patient safety and treatment of malignancies.

scholarly journals Ketorolac-dextran conjugates: Synthesis, in vitro and in vivo evaluation

2007 ◽  
Vol 57 (4) ◽  
pp. 441-450 ◽  
Author(s):  
Savita Vyas ◽  
Piyush Trivedi ◽  
Subhash Chaturvedi
Keyword(s):  
Human Plasma ◽  
Parent Drug ◽  
Aqueous Solubility ◽  
Spectrophotometric Analysis ◽  
In Vivo Evaluation ◽  
Gastrointestinal Side Effects ◽  
Molecular Masses ◽  
Anti Inflammatory

Ketorolac-dextran conjugates: Synthesis,in vitroandin vivoevaluationKetorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. Invitrohydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics.In vivobiological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

scholarly journals Interferon beta-1a induces expression of brain-derived neurotrophic factor in human T lymphocytes in vitro and not in vivo

2020 ◽  
Vol 15 (1) ◽  
pp. FNL38 ◽  
Author(s):  
Zarlascht Karmand ◽  
Hans-Peter Hartung ◽  
Oliver Neuhaus
Keyword(s):  
T Cell ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
Peripheral Blood Lymphocytes ◽  
T Cell Proliferation ◽  
Bdnf Expression ◽  
Healthy Donors

Aim: To detect IFN β-1a-induced expression of brain-derived neurotrophic factor (BDNF) to undermine the hypothesis of IFN β-1a-associated neuroprotection in multiple sclerosis (MS). Methods: The influence of IFN β-1a on in vitro activated peripheral blood lymphocytes from healthy donors was tested. Proliferation analyses were made to detect T-cell growth. BDNF expression was measured by standard ELISA. To assess the influence of IFN β-1a on BDNF expression in vivo, BDNF serum levels of MS patients treated with IFN β-1a were compared with those of untreated patients. Results: IFN β-1a inhibited T-cell proliferation dose dependently. It induced BDNF expression at middle concentrations. MS patients treated with IFN β-1a exhibited significantly lower BDNF serum levels than untreated patients. Conclusion: IFN β-1a may promote neuroprotection by inducing BDNF expression, but its importance in vivo remains open.

scholarly journals ELISA detection of MPO-DNA complexes in human plasma is error-prone and yields limited information on neutrophil extracellular traps formed in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250265
Author(s):  
Hubert Hayden ◽  
Nahla Ibrahim ◽  
Johannes Klopf ◽  
Branislav Zagrapan ◽  
Lisa-Marie Mauracher ◽  
...  
Keyword(s):  
Human Plasma ◽  
Dynamic Range ◽  
Neutrophil Extracellular Traps ◽  
Plasma Samples ◽  
Dna Complexes ◽  
High Background ◽  
Isotype Control ◽  
Extracellular Traps

Over the past years, neutrophil extracellular traps (NETs) were shown to contribute to states of acute and chronic inflammatory disease. They are composed of expelled chromatin and decorated by neutrophil-derived proteins. Therefore, the analysis of DNA complexes with myeloperoxidase (MPO) by ELISA has become an attractive tool to measure NET formation in in vitro and in vivo samples. When we used a published MPO-DNA ELISA protocol and included an isotype control for the anti-MPO coating antibody, we observed high assay specificity for in vitro prepared NET samples, whereas the specificity for in vivo plasma samples was low. In addition, the assay failed to detect in vitro generated MPO-DNA complexes when spiked into plasma. Therefore, we set out to improve the specificity of the MPO-DNA ELISA for plasma samples. We found that the use of Fab fragments or immunoglobulins from different species or reversal of the antibody pair led to either a high background or a low dynamic range of detection that did not improve the specificity for plasma samples. Also, the use of higher plasma dilutions or pre-clearing of plasma immunoglobulins were ineffective. Finally, we found that a commercial reagent designed to block human anti-mouse antibodies and multivalent substances increased the detection window between the MPO antibody and isotype control for highly diluted plasma. We applied this modified ELISA protocol to analyze MPO-DNA complexes in human blood samples of acute and chronic inflammatory conditions. While markers of neutrophil activation and NET formation such as MPO, elastase and citrullinated histone H3 correlated significantly, we observed no correlation with the levels of MPO-DNA complexes. Therefore, we conclude that ELISA measurements of MPO-DNA complexes in human plasma are highly questionable regarding specificity of NET detection. In general, plasma analyses by ELISA should more frequently include isotype controls for antibodies to demonstrate target specificity.

scholarly journals Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Stef De Lombaerde ◽  
Ken Kersemans ◽  
Sara Neyt ◽  
Jeroen Verhoeven ◽  
Christian Vanhove ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Hepatobiliary Transport ◽  
Bile Acid Transporters ◽  
Significant Difference ◽  
The Impact

Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.

scholarly journals Gene expression–based discovery of atovaquone as a STAT3 inhibitor and anticancer agent

Blood ◽  
2016 ◽  
Vol 128 (14) ◽  
pp. 1845-1853 ◽  
Author(s):  
Michael Xiang ◽  
Haesook Kim ◽  
Vincent T. Ho ◽  
Sarah R. Walker ◽  
Michal Bar-Natan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Retrospective Study ◽  
Human Plasma ◽  
Patient Outcomes ◽  
Anticancer Agent ◽  
Plasma Concentrations ◽  
Anticancer Efficacy ◽  
Key Points

Key PointsThe FDA-approved drug atovaquone is a novel, clinically available inhibitor of STAT3 at standard human plasma concentrations. Atovaquone shows anticancer efficacy in vitro, in vivo, and in a retrospective study of AML patient outcomes after atovaquone treatment.

DETECTION OF INACTIVATED α2-MACROGLOBULIN (α2M) IN HUMAN PLASMA USING MONOCLONAL ANTIBODIES

1987 ◽  
Author(s):  
J Abbink ◽  
J Nuijens ◽  
C Huijbregts ◽  
E Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Longitudinal Studies ◽  
Human Plasma ◽  
Dextran Sulfate ◽  
Optimal Conditions ◽  
Α2 Macroglobulin ◽  
In Vitro Activation

Monoclonal antibodies (mAbs) were raised against human a2M. Five mAbs that bound to α2M in ELISA were further analyzed by a radioimmunoassay (RIA) for their reaction with three types of α2M: native α2M, chemically inactivated α2M (iα2M) (methylamine treated), and proteolytically iα2M. One mAb reacted with all forms of α2M, while four mAbs bound both forms of ia2M but not native α2M. One of these latter mAbs (Ml) was used to develop a RIA (the Ml-assay) for the detection of iα2M in plasma: Ml coupled to Sepharose is incubated with the plasma to be tested, and bound iα2M is detected by a subsequent incubation with polyclonal 125I-anti-α2M antibodies. As little as 5 ng of iα2M can be detected with this assay in the presence of an excess of native α2M. This assay was then applied to measure inactivation of α2M in vitro and in vivo. In vitro activation of the contact system in plasma by dextran sulfate results in the inactivation of ca 10% of α2M. When blood from normal donors was collected under optimal conditions, about 0.5% of the total α2M content appeared to be iα2M. Longitudinal studies in patients (a.o. with septicaemie, during cardiopulmunary bypass) revealed that increased levels of iα2M occurred sporadically. The Ml-assay appears to be useful to monitor the role of α2M in human diseases.

scholarly journals Neutrophils express the high affinity receptor for IgG (Fc gamma RI, CD64) after in vivo application of recombinant human granulocyte colony- stimulating factor

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 885-889 ◽  
Author(s):  
R Repp ◽  
T Valerius ◽  
A Sendler ◽  
M Gramatzki ◽  
H Iro ◽  
...  
Keyword(s):  
Fc Receptors ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
High Affinity ◽  
Healthy Donors ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Stimulating Factor

Abstract Fc receptors are important effector molecules of neutrophilic granulocytes (polymorphonuclear neutrophils [PMN]), connecting phagocytic cells and the specific immune response. Neutrophils from healthy donors express the low-affinity receptors for IgG Fc gamma RII (CD32) and Fc gamma RIII (CD16), but not the high-affinity receptor Fc gamma RI (CD64). The latter has been found on neutrophils from patients with certain bacterial infections and can be induced in vitro after incubation with interferon-gamma. We show here that neutrophils strongly express Fc gamma RI after in vivo application of recombinant human granulocyte colony-stimulating factor (rhG-CSF). PMN from patients receiving rhG-CSF displayed higher cytotoxicity against Daudi lymphoma cells in vitro compared with control patients and with healthy donors. Fab fragments against Fc gamma RII (monoclonal antibody [MoAb] IV.3) inhibited neutrophil-mediated cytotoxicity of healthy donors but not of patients during rhG-CSF therapy. Therefore, expression of Fc receptors by PMN was investigated by flow cytometry and the mean fluorescence intensity (MFI) was compared. After staining with MoAb 32.2 against Fc gamma RL, the median MFI of neutrophils from G-CSF patients (median, 4.78; range, 2.40 to 8.50; n = 5) was significantly higher (P = .002 and P = .001, respectively) than the median MFI of patients not receiving G-CSF (median, 1.23; range, 1.01 to 1.58; n = 6) and the median MFI of healthy donors (median, 1.04; range, 0.67 to 1.12; n = 6). Fc gamma RI disappeared after the discontinuing of the G- CSF injections, but was reinduced during the next treatment cycle with rhG-CSF. The high expression of Fc gamma RI during rhG-CSF therapy correlated with enhanced cytotoxicity. In vitro incubation with rhG-CSF also enhances cytotoxicity, but only minor increments in Fc gamma RI expression were observed. Thus, during in vivo application of rhG-CSF neutrophils acquire an additional potent receptor for mediating tumor cell killing in vitro by induction of the high-affinity receptor for IgG (Fc gamma RI, CD64).

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