11 results on '"S. Grancha"'
Search Results
2. The burden of inhibitors in haemophilia patients
- Author
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S. Grancha, Christopher E. Walsh, Víctor Jiménez-Yuste, and Guenter Auerswald
- Subjects
Burden of disease ,medicine.medical_specialty ,Factor VIII ,business.industry ,Hematology ,Health Care Costs ,030204 cardiovascular system & hematology ,Haemophilia ,medicine.disease ,Hemophilia A ,Poor quality ,03 medical and health sciences ,0302 clinical medicine ,Clinical evidence ,Immunology ,von Willebrand Factor ,medicine ,Immune Tolerance ,Quality of Life ,Animals ,Humans ,Cost of care ,Intensive care medicine ,business ,030215 immunology - Abstract
SummaryThe burden of disease in haemophilia patients has wide ranging implications for the family and to society. There is evidence that having a current inhibitor increases the risk of morbidity and mortality. Morbidity is increased by the inability to treat adequately and its consequent disabilities, which then equates to a poor quality of life compared with non-inhibitor patients. The societal cost of care, or `burden of inhibitors’, increases with the ongoing presence of an inhibitor. Therefore, it is clear that successful eradication of inhibitors by immune tolerance induction (ITI) is the single most important milestone one can achieve in an inhibitor patient. The type of factor VIII (FVIII) product used in ITI regimens varies worldwide. Despite ongoing debate, there is in vitro and retrospective clinical evidence to support the use of plasma-derived VWF-containing FVIII concentrates in ITI regimens in order to achieve early and high inhibitor eradication success rates.
- Published
- 2016
3. Albumin function in acute-on-chronic liver failure (ACLF): Effect of plasma exchange with albumin 5% (PE-A5%)
- Author
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A. Páez, Javier Fernández, V. Arroyo, Raquel Horrillo, N. Afonso, M. Torres, S. Grancha, Montserrat Costa, A. Pérez, A.M. Ortiz, and L. Núñez
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,medicine ,Albumin ,Acute on chronic liver failure ,business ,Gastroenterology ,Function (biology) - Published
- 2018
4. Plasma-derived FVIII/VWF complex shows higher protection against inhibitors than isolated FVIII after infusion in haemophilic patients: A translational study.
- Author
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Bravo MI, Pérez A, Raventós A, Grancha S, Jorquera JI, Butta NV, Álvarez-Román MT, Costa M, Willis T, and Jiménez-Yuste V
- Subjects
- Animals, Disease Models, Animal, Immunoglobulin G immunology, Mice, Recombinant Proteins administration & dosage, Factor VIII administration & dosage, Factor VIII immunology, Factor VIII isolation & purification, Hemophilia A therapy, von Willebrand Factor administration & dosage, von Willebrand Factor isolation & purification
- Abstract
Introduction: Presence of von Willebrand factor (VWF) in FVIII concentrates offers protection against neutralizing inhibitors in haemophilia A (HA). Whether this protection is more evident in plasma-derived (pd) FVIII/VWF or recombinant (r) FVIII concentrates remains controversial., Aim: We investigated the protection exerted by VWF against FVIII inhibitors in an in vivo mouse model of HA exposed to pdFVIII/VWF or to various rFVIII concentrates., Methods: Haemophilia A mice received the different FVIII concentrates after administration of vehicle or an inhibitory IgG purified from a commercial pool of HA plasma with inhibitors and FVIII:C recoveries were measured. Furthermore, using a novel clinically oriented ex vivo approach, Bethesda inhibitory activities (BU) of a commercial pool of HA plasma with inhibitors were assessed using normal plasma, or plasma from severe HA patients, without inhibitors, after treatment with the same concentrates., Results: in vivo studies showed that pdFVIII/VWF offers markedly higher protection against inhibitors when compared with any of the FVIII products without VWF. More importantly, in the ex vivo studies, plasma from patients treated with pdFVIII/VWF showed higher protection against inhibitors (P values ranging .05-.001) in comparison with that observed in plasma from patients who received FVIII products without VWF, regardless of the type of product evaluated., Conclusion: Data indicate that FVIII+VWF complexes assembled in the circulation after rFVIII infusion are not equivalent to the naturally formed complex in pdFVIII/VWF. Therefore, rFVIII infused into HA patients with inhibitors would be less protected by VWF than the FVIII in pdFVIII/VWF concentrates., (© 2022 The Authors. Haemophilia published by John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
5. Characterization of antibodies in human immunoglobulin products from different regions worldwide.
- Author
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Serra A, Marzo N, Pons B, Maduell P, López M, and Grancha S
- Subjects
- Americas, Antibodies genetics, Antibodies immunology, Asia, Humans, Immunoenzyme Techniques, Immunoglobulins, Intravenous analysis, Immunoglobulins, Intravenous economics, Neutralization Tests, Plasma chemistry, Plasma immunology, Immunoglobulins, Intravenous immunology
- Abstract
Aim: The antibody levels against a broad spectrum of pathogens were assessed in commercial intravenous immunoglobulin (IVIG) manufactured from pooled plasma obtained from different global regions., Methods: Twenty-four IVIG commercial lots from eight manufacturers corresponding to 12 brands were analyzed. The plasma was collected in 10 countries/regions. Depending on each pathogen, antibody levels were measured using specific commercial IgG-specific enzyme immunoassay kits or by cell culture neutralization test and guinea pig skin neutralization test. A principal component analysis was performed., Results: For polio and diphtheria (reference markers of the US authorities), all IVIGs had relevant titers in accordance with reference levels. IVIGs from Canada, Australia, and the USA were positive for titers against globally distributed pathogens or those under vaccination programs in the developed world (parainfluenza, Epstein-Barr, varicella-zoster, influenza B, parvovirus B19, and measles viruses). IVIG from Taiwan and Hong Kong showed low antibody titers for these pathogens but high titers for Pseudomonas aeruginosa. IVIG from India had high titers for pathogens frequently found in developing countries (West Nile, dengue, chikungunya, and hepatitis E viruses and Streptococcus pneumoniae). IVIGs from Argentina, Spain, Israel, and Czechia showed intermediate antibody concentrations., Conclusion: The antibody profile in IVIG was greatly influenced by regional characteristics including climate, vaccination programs, and the prevalence of pathogens in the different countries and regions., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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6. Cross-Sectional Characterization of Albumin Glycation State in Cerebrospinal Fluid and Plasma from Alzheimer's Disease Patients.
- Author
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Costa M, Mestre A, Horrillo R, Ortiz AM, Pérez A, Ruiz A, Boada M, and Grancha S
- Subjects
- Aged, Alzheimer Disease cerebrospinal fluid, Case-Control Studies, Chromatography, Liquid, Female, Glycation End Products, Advanced, Humans, Male, Mass Spectrometry, Middle Aged, Oxidation-Reduction, Serum Albumin cerebrospinal fluid, Glycated Serum Albumin, Alzheimer Disease metabolism, Oxidative Stress, Protein Processing, Post-Translational, Serum Albumin metabolism
- Abstract
We determined albumin post-translational modifications (PTMs) by mass spectrometry (MS) in plasma and cerebrospinal fluid (CSF) from 31 Alzheimer's disease (AD) patients (with 27 samples of paired plasma-CSF from the same patients). Results were cross-sectionally compared with healthy controls. For percentage of relative intensity of glycated isoforms, plasma albumin was globally more glycated in AD patients than in healthy controls (P<0.01). MS results in plasma were confirmed by a quantitative enzymatic assay (Lucica GA-L) for albumin early-glycation detection. In CSF there were no global glycation differences detected by MS, although a different pattern of glycated isoforms was observed. Oxidized+glycated and cysteinylated+glycated isoforms were increased in both plasma and CSF of AD patients in comparison with healthy controls (P<0.001). Furthermore, AD patients showed higher glycation in plasma than in CSF (P<0.01). Our data support the role of glycation and oxidative stress in AD., Competing Interests: MC, AM, RH, AMO, AP and SG are employees of Grifols, a manufacturer of plasma derivatives. MB has consulted for Araclon, Avid, Grifols, Lilly, Nutricia, Roche and Servier. She received fees for lectures, and/or reimbursement of expenses for congresses attendance, and/or funds for research from Araclon, Grifols, Nutricia, Roche and Servier. She has not received personal compensations from these organizations. AR has consulted for Grifols. He is a member of the scientific advisory board of Landsteiner Genmed. He received funds for research from Araclon, Grifols, Nutricia, Roche and Servier. He received reimbursement of expenses for congresses attendance from Araclon, Grifols, and Landsteiner Genmed. He has not received personal compensations from these organizations..
- Published
- 2019
- Full Text
- View/download PDF
7. Increased Albumin Oxidation in Cerebrospinal Fluid and Plasma from Alzheimer's Disease Patients.
- Author
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Costa M, Horrillo R, Ortiz AM, Pérez A, Mestre A, Ruiz A, Boada M, and Grancha S
- Subjects
- Aged, Aged, 80 and over, Amyloid beta-Peptides blood, Amyloid beta-Peptides cerebrospinal fluid, Case-Control Studies, Chromatography, High Pressure Liquid, Female, Humans, Male, Middle Aged, Principal Component Analysis, Albumins metabolism, Alzheimer Disease blood, Alzheimer Disease cerebrospinal fluid, Serum Albumin metabolism, Serum Albumin, Human metabolism
- Abstract
Background: Oxidative stress in the brain and peripheral systems is considered a major player in Alzheimer's disease (AD). Albumin is the main transporter and the main extracellular antioxidant in the human body., Objective: Here we explore for the first time the oxidation status of cerebrospinal fluid (CSF) and plasma albumin in AD in comparison to healthy subjects., Methods: Plasma and CSF samples were obtained from mild-moderate AD patients and control healthy age-matched donors. Albumin redox state forms (reduced: HMA; reversibly oxidized: HNA1; irreversibly oxidized: HNA2) were determined by HPLC. Albumin post-translational modifications (PTM) analysis was performed by mass spectrometry., Results: HPLC showed less HMA in AD plasma than in controls (54.1% versus 65.2% ; p < 0.0001), mainly at expense of HNA1 (42.8% versus 32.5% ; p < 0.0001). In AD CSF, HMA was drastically decreased compared to controls (9.6% versus 77.4% ; p < 0.0001), while HNA2 was increased (52.8% versus 7.4% ; p < 0.0001). In AD patients but not in healthy controls, CSF albumin was much more irreversibly oxidized than in plasma (close to 20-fold increase in HNA2). PTM analysis showed that AD CSF albumin samples behave as a differentiated cluster, thus confirming the albumin oxidative pattern observed by HPLC., Conclusion: CSF albumin oxidation in AD patients was dramatically increased comparing to healthy controls, while in plasma this increase was smaller. CSF albumin in AD patients was much more oxidized than in plasma, but this effect was not observed in healthy controls. These results suggest that albumin oxidation, especially in CSF, and its role in AD deserves further investigation.
- Published
- 2018
- Full Text
- View/download PDF
8. Human mesenchymal stem cells maintain their phenotype, multipotentiality, and genetic stability when cultured using a defined xeno-free human plasma fraction.
- Author
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Blázquez-Prunera A, Díez JM, Gajardo R, and Grancha S
- Subjects
- Cell Differentiation, Cells, Cultured, Culture Media chemistry, Genomic Instability, Humans, Intercellular Signaling Peptides and Proteins pharmacology, Karyotype, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Phenotype, Plasma chemistry, Culture Media pharmacology, Mesenchymal Stem Cells drug effects, Primary Cell Culture methods
- Abstract
Background: Mesenchymal stem cells (MSCs) show promising characteristics for their use in advanced therapy medicinal products. However, there are some unresolved concerns, such as the use of animal components for their expansion. In this study we assessed the suitability of a xeno-free supplement for cell culture (SCC) derived from human plasma, to culture and expand human MSCs (hMSCs) from different origins. Characteristics of viable cultured hMSCs such as genetic stability, phenotype and multipotentiality were qualitatively evaluated., Methods: hMSCs from adipose tissue (AT), bone marrow (BM) and umbilical cord (UC) and supplier sources (commercial/non-commercial) were used. After hMSCs expansion in a xeno-free medium, classical hMSCs markers were studied by immunocytochemistry, and genetic stability was tested by classic karyotyping. The capacity of hMSCs to differentiate into adipogenic, osteogenic, and chondrogenic cells in differentiation media was assessed using different staining. Different lots of SCC were used to assure consistency between batches., Results: All hMSCs tested maintained their morphology and adherence to plastic during their expansion, and preserved their genetic stability, phenotype and differentiation potential. No differences were observed when using different lots of SCC. Moreover, the proliferation rate, evaluated as population doubling time (PDT) of commercial BM and AT hMSCs, was higher in the xeno-free medium than in the control media provided by the suppliers of the cells (PDT of 4.6 for BM-hMSC and 6.4 for AT-hMSC in xeno-free medium, and 7.0 and 14.7 respectively in the commercial media). UC-hMSCs PDT was similar in all the media tested. When using non-commercial BM-hMSCs, PDT was lower in the xeno-free medium, but reverted to the control level with the addition of growth factors., Conclusions: SCC-containing medium can be a feasible xeno-free alternative to expand hMSCs for advanced therapies.
- Published
- 2017
- Full Text
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9. The burden of inhibitors in haemophilia patients.
- Author
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Walsh CE, Jiménez-Yuste V, Auerswald G, and Grancha S
- Subjects
- Animals, Factor VIII immunology, Health Care Costs, Hemophilia A drug therapy, Humans, Immune Tolerance, Quality of Life, von Willebrand Factor immunology, Hemophilia A immunology, Hemophilia A mortality
- Abstract
The burden of disease in haemophilia patients has wide ranging implications for the family and to society. There is evidence that having a current inhibitor increases the risk of morbidity and mortality. Morbidity is increased by the inability to treat adequately and its consequent disabilities, which then equates to a poor quality of life compared with non-inhibitor patients. The societal cost of care, or `burden of inhibitors', increases with the ongoing presence of an inhibitor. Therefore, it is clear that successful eradication of inhibitors by immune tolerance induction (ITI) is the single most important milestone one can achieve in an inhibitor patient. The type of factor VIII (FVIII) product used in ITI regimens varies worldwide. Despite ongoing debate, there is in vitro and retrospective clinical evidence to support the use of plasma-derived VWF-containing FVIII concentrates in ITI regimens in order to achieve early and high inhibitor eradication success rates.
- Published
- 2016
- Full Text
- View/download PDF
10. Neutralizing capacity of inhibitors on FVIII is lower for natural FVIII/VWF complex than for isolated FVIII: in vitro comparative study in eleven different therapeutic FVIII concentrates.
- Author
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Bravo MI, Ortiz AM, Costa M, Grancha S, and Jorquera JI
- Subjects
- Antibodies, Neutralizing blood, Coagulants therapeutic use, Drug Combinations, Factor VIII genetics, Factor VIII therapeutic use, Hemophilia A drug therapy, Humans, Recombinant Proteins biosynthesis, Recombinant Proteins immunology, Recombinant Proteins therapeutic use, von Willebrand Factor therapeutic use, Antibodies, Neutralizing immunology, Coagulants immunology, Factor VIII immunology, von Willebrand Factor immunology
- Published
- 2016
- Full Text
- View/download PDF
11. Native plasma-derived FVIII/VWF complex has lower sensitivity to FVIII inhibitors than the combination of isolated FVIII and VWF proteins. Impact on Bethesda assay titration of FVIII inhibitors.
- Author
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Bravo MI, Da Rocha-Souto B, Grancha S, and Jorquera JI
- Subjects
- Blood Coagulation drug effects, Blood Coagulation immunology, Blood Coagulation Factor Inhibitors immunology, Blood Coagulation Tests methods, Drug Combinations, Factor VIII antagonists & inhibitors, Factor VIII immunology, Hemophilia A diagnosis, Hemophilia A immunology, Humans, Isoantibodies immunology, Kinetics, Protein Binding immunology, Thrombin metabolism, von Willebrand Factor antagonists & inhibitors, von Willebrand Factor immunology, Blood Coagulation Factor Inhibitors blood, Factor VIII pharmacokinetics, Hemophilia A blood, Hemophilia A drug therapy, Isoantibodies blood, von Willebrand Factor pharmacokinetics
- Abstract
Sensitivity to FVIII inhibitors of the native plasma-derived (pd) FVIII/VWF complex vs. the complexes formed after exogenous FVIII infusion in the haemophilic patient has not been thoroughly studied. The role of VWF in the interaction of FVIII with inhibitors was studied in vitro using different combinations of VWF and FVIII concentrates. Normal plasma, pdFVIII/VWF and isolated FVIII (recombinant FVIII, B-domain deleted and pdFVIII) were used. Titre (BU) was kinetically determined (up to 2 h) in serial dilutions of inhibitor IgG (purified from a pool of plasmas with inhibitors) mixed with VWF and then incubated with the different FVIII. Inhibitor was also added to previously mixed VWF+FVIII. Residual FVIII:C was determined. TGA assays were performed with FVIII-deficient plasma spiked with the FVIII-VWF mixtures with/without an ESH-8 antibody. Inhibitor titres for plasma and pdFVIII/VWF were comparable at all time points. Titres for all concentrates of isolated FVIII were significantly higher than those for plasma or pdFVIII/VWF (1.4-1.9 fold) even after preincubation with VWF. At t = 0 h, titres for plasma or pdFVIII/VWF were unquantifiable, but were detectable for isolated FVIII (0.6-1.6 BU). In contrast to pdFVIII/VWF, the decrease in thrombin generation parameters by isolated FVIII in the presence of ESH-8 was significant (P < 0.01) even when previously combined with VWF. In conclusion, VWF protection against FVIII inhibitor activity might be higher with native pdFVIII/VWF complex than with the corresponding compound formed from the isolated proteins. Bethesda assay titration using different FVIII concentrates would be advisable to guide the treatment of inhibitor patients., (© 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
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