Elevated Fibrinogen Level Reduces Therapeutic Efficiency of AD Drugs: Biophysical Insights into the Interaction of FDA-Approved Cholinesterase Inhibitors with Human Fibrinogen

2021 ◽  
Author(s):  
Prayasee Baruah ◽  
Debojit Paul ◽  
Jitesh Doshi ◽  
Sivaprasad Mitra
Keyword(s):  
Cholinesterase Inhibitors ◽  
Fibrinogen Level ◽  
Human Fibrinogen ◽  
Therapeutic Efficiency

Demonstration of heterodimeric fibrinogen molecules partially conjugated with albumin in a novel dysfibrinogen: Fibrinogen Mannheim V

2009 ◽  
Vol 102 (07) ◽  
pp. 29-34 ◽  
Author(s):  
Peter M.George ◽  
Martin Borggrefe ◽  
Michael Neumaier ◽  
Stephen O. Brennan ◽  
Carl-Erik Dempfle
Keyword(s):  
Molecular Weight ◽  
Fibrinogen Level ◽  
Fibrinopeptide A ◽  
Intermediate Result ◽  
Plasma Fibrinogen Level ◽  
Human Fibrinogen ◽  
Single Nucleotide ◽  
Single Nucleotide Deletion ◽  
Laboratory Screening ◽  
Sds Page

SummaryA 30-year-old female experienced three miscarriages in early pregnancy. Extensive laboratory screening showed a low plasma fibrinogen level of approximately 1 g/l detected by PT-derived fibrinogen assay.The fibrinogen level in the immunological assay was 3 g/l.The functional Clauss assay yielded an intermediate result of 1.78 g/l. During her fourth and fifth pregnancy, the patient received fibrinogen concentrates (Haemocomplettan, CLS Behring, Marburg, Germany), starting with 4 grams of human fibrinogen, followed by 2 grams every second day until the 15th week of pregnancy.The further course of these pregnancies was uneventful. SDS-PAGE and immunoblotting showed doublet bands in the positions of the high-molecular weight (HMW)-and lowmolecular-weight (LMW)-fibrinogen, a single LMW’ fibrinogen band, plus additional bands with higher molecular weight than HMW-fibrinogen, which were also reactive with anti-human serum albumin (HSA) antiserum. These bands correspond to variant fibrinogen conjugated with albumin. Reduced SDS-PAGE and immunoblotting using polyclonal anti-fibrinopeptide A antiserum disclosed one additional Aα-chain band with lower molecular weight. Amplification and sequencing of exon 5 of the α gene indicated heterozygosity for a novel single nucleotide deletion at codon Aα494 (C1537delA). His494 is replaced by Pro and this is followed by 23 (LMKLPSSTLPQLEKHSQ VSSHLC) new amino acids before premature truncation after Cys517, yielding a free C-terminal cysteine, which may link with albumin.This new fibrinogen mutation, leads to a balanced array of homo- and heterodimeric fibrinogen molecules, some of which are conjugated to albumin.

scholarly journals Polymorphisms of the Fibrinogen-Beta Gene are Related to 2-Hour Glucose Level after Oral Glucose Tolerance Test in Hong Kong Chinese

2008 ◽  
Vol 24 (3) ◽  
pp. 167-173 ◽  
Author(s):  
Louisa Y. F. Wong ◽  
Kwok Leung Ong ◽  
Bernard M. Y. Cheung ◽  
Raymond Y. H. Leung ◽  
Yu Bun Man ◽  
...  
Keyword(s):  
Hong Kong ◽  
Glucose Tolerance ◽  
Fibrinogen Level ◽  
Plasma Fibrinogen ◽  
Hong Kong Chinese ◽  
Stepwise Multiple Regression ◽  
Oral Glucose ◽  
Oral Glucose Load ◽  
Glucose Load ◽  
Human Fibrinogen

Fibrinogen, an acute phase protein, is an important inflammatory marker that is associated with cardiovascular diseases. We studied the association of three common human fibrinogen-βgene (FGB) variants, −455G>A, −249C>T, and −148C>T with glycemic parameters in 265 non-diabetic Hong Kong Chinese subjects. BothFGBvariants, −455G>A and −148C>T were in complete linkage disequilibrium and were associated with higher levels of plasma fibrinogen and 2-h glucose after a 75-g oral glucose load (p<0.01). Carriers ofFGBAC-haplotype, comprising the two nucleotide variants at positions −455 and −249, had higher fibrinogen level (2.64 ± 0.65 vs 2.42 ± 0.52 g/L,p= 0.002) and 2-h glucose after a 75-g oral glucose load (5.87 ± 1.14 vs 5.47 ± 1.22 g/L,p= 0.006). The associations were significant in men, but not women. In stepwise multiple regression analysis, AC-haplotype was independently associated with plasma fibrinogen level and 2-h glucose (p= 0.002 and 0.010 respectively). This suggests that fibrinogen may play a role in the development of impaired glucose tolerance.

Quantitation of the Coagulation Inhibition in Vivo Due to Breakdown Products of Fibrin

1970 ◽  
Vol 23 (03) ◽  
pp. 477-485 ◽  
Author(s):  
P. S Mitchell ◽  
F. K Beller
Keyword(s):  
Blood Clotting ◽  
Fibrinogen Level ◽  
Degradation Products ◽  
Thrombin Time ◽  
Clotting Time ◽  
Human Fibrinogen ◽  
Quantitative Basis ◽  
Coagulation Inhibition

SummaryDegradation products of human fibrinogen were prepared by in vitro lysis of fibrin clots by urokinase activation and injected into rabbits on a quantitative basis. The dose necessary to anticoagulate the animal was equal to 2½ to 3 times the animals’ fibrinogen level. The effect on whole blood clotting time and thrombin time lasted for approximately 2 hrs. The “r” time of the TEG returned to normal after 1 hr while the “Max” value remained abnormal for more than 120 min. Degradation product E was shown to clear more rapidly than D by immunochemical techniques. The overall T ½ clearance was found to be approximately 12 hrs.

Assessing Cholinesterase Inhibitors

2007 ◽  
Vol 40 (18) ◽  
pp. 8-9
Author(s):  
THOMAS FINUCANE
Keyword(s):  
Cholinesterase Inhibitors

Adenosine Diphosphate-Induced Aggregation of Human Platelets in Flow Through Tubes: III. Shear and Extrinsic Fibrinogen-Dependent Effects

1994 ◽  
Vol 71 (01) ◽  
pp. 078-090 ◽  
Author(s):  
H L Goldsmith ◽  
M M Frojmovic ◽  
Susan Braovac ◽  
Fiona McIntosh ◽  
T Wong
Keyword(s):  
Shear Rate ◽  
Single Cells ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Size Analysis ◽  
Fibrinogen Concentration ◽  
Human Fibrinogen ◽  
Shear Rates ◽  
Rate Dependent ◽  
Induced Aggregation

SummaryThe effect of shear rate and fibrinogen concentration on adenosine diphosphate-induced aggregation of suspensions of washed human platelets in Poiseuille flow at 23°C was studied using a previously described double infusion technique and resistive particle counter size analysis (1). Using suspensions of multiple-centrifuged and -washed cells in Tyrodes-albumin [3 × 105 μl−1; (17)] with [fibrinogen] from 0 to 1.2μM, the, rate and extent of aggregation with 0.7 μM ADP in Tyrodes-albumin were measured over a range of mean transit times from 0.2 to 43 s, and at mean tube shear rates, Ḡ, = 41.9, 335 and 1,335 s−1. As measured by the decrease in singlet concentration, aggregation at 1.2 μM fibrinogen increased with increasing Ḡ up to 1,335 s1, in contrast to that previously reported in citratcd plasma, in which aggregation reached a maximum at Ḡ = 335 s−1. Without added fibrinogen, there was no aggregation at Ḡ = 41.9 s1; at Ḡ = 335 s1, there was significant aggregation but with an initial lag time, aggregation increasing further at Ḡ = 1,335 s−1. Without added fibrinogen, aggregation was abolished at all Ḡ upon incubation with the hexapeptide GRGDSP, but was almost unaffected by addition of an F(ab’)2 fragment of an antibody to human fibrinogen. Aggregation in the absence of added fibrinogen was also observed at 37°C. The activation of the multiple-washed platelets was tested using flow cytometry with the fluorescently labelled monoclonal antibodies FITC-PAC1 and FITC-9F9. It was shown that 57% of single cells in unactivated PRT expressed maximal GPIIb-IIIa fibrinogen receptors (MoAb PAC1) and 54% expressed pre-bound fibrinogen (MoAb 9F9), with further increases on ADP activation. However, incubation with GRGDSP and the F(ab’)2 fragment did not inhibit the prebound fibrinogen. Moreover, relatively unactivated cells (8% expressing receptor, 14% prebound fibrinogen), prepared from acidified cPRP by single centrifugation with 50 nM of the stable prostacyclin derivative, ZK 36 374, and resuspension in Tyrodes-albumin at 5 × 104 μl−1, aggregated with 2 and 5 μM ADP at Ḡ = 335 and 1,335 s−1 in the absence of added fibrinogen. We therefore postulate that a protein such as von Willebrand factor, secreted during platelet isolation or in flow at sufficiently high shear rates, may yield the observed shear-rate dependent aggregation without fibrinogen.

Isolation of Human Fibrinogen and its Derivatives by Affinity Chromatography on Gly-Pro-Arg-Pro-Lys-Fractogel

1990 ◽  
Vol 63 (03) ◽  
pp. 439-444 ◽  
Author(s):  
C Kuyas ◽  
A Haeberli ◽  
P Walder ◽  
P W Straub
Keyword(s):  
Gel Electrophoresis ◽  
Affinity Purification ◽  
Polyacrylamide Gel Electrophoresis ◽  
Ease Of Use ◽  
Terminal Sequence ◽  
Purification Method ◽  
Human Fibrinogen ◽  
Isolation Methods ◽  
One Step ◽  
Complementary Binding

SummaryWith an immobilized synthetic pentapeptide GlyProArgProLys comprising the N-terminal sequence GlyProArg of the α-chain of fibrin, a new affinity method for the quantitative isolation of fibrinogen out of anticoagulated plasma was developed. The method proved to be superior to all known isolation methods in respect to ease of use and yield, since fibrinogen could be isolated in one step out of plasma with a recovery of more than 95% when compared to the immunologically measurable amounts of fibrinogen. Moreover the amounts of contaminating proteins such as fibronectin, factor XIII or plasminogen were negligible and the purity of the isolated fibrinogen was higher than 95% as measured by polyacrylamide gel electrophoresis. The clottability was 90% and more. Another advantage of this affinity purification method is the possibility to isolate fibrinogen quantitatively out of small plasma samples (<5 ml). Further, abnormal fibrinogen molecules, provided their complementary binding site for GlyProArg is preserved, may also be quantitatively isolated independent of any solubility differences as compared to normal fibrinogen. In addition fibrin(ogcn) fragments originating from plasmic digestion can be separated on the basis of their affinity to GlyProArg. The described affinity gel can be used more than 50 times without any loss of capacity.

Structural Aspects on the Glycosylation Sites in Human Fibrinogen

1979 ◽  
Vol 41 (04) ◽  
pp. 671-676 ◽  
Author(s):  
Edda Töpfer-Petersen ◽  
Friedrich Lottspeich ◽  
Agnes Henschen
Keyword(s):  
Human Fibrinogen ◽  
Glycosylation Sites ◽  
Structural Aspects
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