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British Journal of Clinical Pharmacology Jun 2019A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy...
AIMS
A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery.
METHODS
An intravenous infusion of 3 mL/kg 20% albumin over 30 minutes was given to 15 volunteers and to 15 patients on the 1 day after major open abdominal surgery. Blood samples and urine were collected during 5 hours. Mixed-effect modelling software was used to develop a fluid volume kinetic model, using blood haemoglobin and urine excretion the estimate body fluid shifts, to which individual-specific covariates were added in sequence.
RESULTS
The rise in plasma albumin expanded the plasma volume in excess of the infused volume by relocating noncirculating fluid (rate constant k ), but it also increased losses of fluid from the kinetic system (k ). The balance between k and k maintained the rise in plasma albumin and plasma volume at a virtual steady-state for almost 2 hours. The rate constant for urinary excretion (k ) was slightly reduced by the preceding surgery, by a marked rise in plasma albumin, and by a high preinfusion urinary concentration of creatinine. The arterial pressure, body weight, and plasma concentrations of C-reactive protein and shedding products of the endothelial glycocalyx layer (syndecan-1, heparan sulfate, and hyaluronic acid) did not serve as statistically significant covariates.
CONCLUSIONS
There were no clinically relevant differences in the kinetics of 20% albumin between postoperative patients and volunteers.
Topics: Abdomen; Adult; Albumins; Female; Fluid Shifts; Fluid Therapy; Humans; Infusions, Intravenous; Male; Models, Biological; Plasma Substitutes; Postoperative Care; Sweden; Treatment Outcome; Young Adult
PubMed: 30756411
DOI: 10.1111/bcp.13897 -
Journal of Hepatology Nov 2013
Topics: Albumins; End Stage Liver Disease; Female; Humans; Liver; Male; Oxidative Stress
PubMed: 23954671
DOI: 10.1016/j.jhep.2013.08.001 -
Acta Poloniae Pharmaceutica 2013Albumin is one of the most extensively studied endogenous proteins which are used in the fabrication of drug delivery and diagnostic technologies during last 10 years.... (Review)
Review
Albumin is one of the most extensively studied endogenous proteins which are used in the fabrication of drug delivery and diagnostic technologies during last 10 years. This review provides a summary of products involving the use of albumin as a drug delivery tool for getting better the pharmacokinetics of a drug by developing the targetted drug delivery systems and diagnosing the pathologies. Using albumin, following market approved products have been developed: Levemir and Victoza (antidiabetic product), Abraxane (antimetastatic breast cancer product), and Nanocoll and Albures (for lymphoscintigraphy and diagnosis of cancer and rheumatoid arthritis).
Topics: Albumin-Bound Paclitaxel; Albumins; Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Drug Carriers; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Liraglutide; Paclitaxel; Predictive Value of Tests; Radiopharmaceuticals; Technetium Tc 99m Aggregated Albumin
PubMed: 23923383
DOI: No ID Found -
Journal of Nanobiotechnology May 2021In this article, we will describe the properties of albumin and its biological functions, types of sources that can be used to produce albumin nanoparticles, methods of... (Review)
Review
In this article, we will describe the properties of albumin and its biological functions, types of sources that can be used to produce albumin nanoparticles, methods of producing albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations. In view of the increasing use of Abraxane and its approval for use in the treatment of several types of cancer and during the final stages of clinical trials for other cancers, to evaluate it and compare its effectiveness with conventional non formulations of chemotherapy Paclitaxel is paid. In this article, we will examine the role and importance of animal proteins in Nano medicine and the various benefits of these biomolecules for the preparation of drug delivery carriers and the characteristics of plant protein Nano carriers and protein Nano cages and their potentials in diagnosis and treatment. Finally, the advantages and disadvantages of protein nanoparticles are mentioned, as well as the methods of production of albumin nanoparticles, its therapeutic applications and the importance of albumin nanoparticles in the production of pharmaceutical formulations.
Topics: Albumin-Bound Paclitaxel; Albumins; Animals; Drug Carriers; Drug Compounding; Drug Delivery Systems; Gelatin; Humans; Milk Proteins; Nanoparticles; Neoplasms; Paclitaxel; Plant Proteins; Serum Albumin
PubMed: 34051806
DOI: 10.1186/s12951-021-00896-3 -
International Journal of Molecular... Sep 2019Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of...
Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of action is not fully understood. Several SeCs have been reported to have albumin-binding ability, which is an important factor in determining the treatment efficacy of drugs. In the present investigation, we hypothesized that extracellular albumin might orchestrate SeCs efficacy. Four SeCs representing distinct categories were selected to investigate their cytotoxicity, cellular uptake, and species transformation. Concomitant treatment of albumin greatly decreased cytotoxicity and cellular uptake of SeCs. Using both X-ray absorption spectroscopy and hyphenated mass spectrometry, we confirmed the formation of macromolecular conjugates between SeCs and albumin. Although the conjugate was still internalized, possibly via albumin scavenger receptors expressed on the cell surface, the uptake was strongly inhibited by excess albumin. In summary, the present investigation established the importance of extracellular albumin binding in determining SeCs cytotoxicity. Due to the fact that albumin content is higher in humans and animals than in cell cultures, and varies among many patient categories, our results are believed to have high translational impact and clinical implications.
Topics: Albumins; Cell Survival; Molecular Structure; Reactive Oxygen Species; Sequestering Agents; Spectrum Analysis
PubMed: 31554226
DOI: 10.3390/ijms20194734 -
Chemical & Pharmaceutical Bulletin 2022Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high... (Review)
Review
Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high biocompatibility, and a wide variety of drug binding abilities. Albumin is known to distribute widely in the blood and various interstitial fluids and organs. Different albumin receptors skillfully regulate the distribution characteristics of albumin in the body. Albumin receptors are a group of diverse proteins, such as FcRn, gp60, gp18, megalin, cubilin, SPARC, and CD36. Their tissue distributions in vivo are unique, with different albumin's recognition sites. Therefore, the distribution of albumin in vivo is ingeniously controlled by these multiple albumin receptors. Reevaluation of these albumin receptors opens up new possibilities for applying albumin as a drug delivery carrier. If the tissue distributions of albumin receptors were known and the albumin recognition site of the receptor was identified, organ-specific active targeting would be possible. In this review, we would like to scrutinize what is currently known and share information to develop next-generation albumin carriers that focus on interactions with albumin receptors.
Topics: Albumins; Drug Delivery Systems; Excipients; Humans; Receptors, Albumin; Tissue Distribution
PubMed: 35491188
DOI: 10.1248/cpb.c21-01024 -
Transfusion and Apheresis Science :... Jun 2021Alzheimer's disease (AD) is a neurodegenerative process that inexorably leads to progressive deterioration of cognition function and, ultimately, death. Central... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative process that inexorably leads to progressive deterioration of cognition function and, ultimately, death. Central pathophysiologic features of AD include the accumulation of extracellular plaques comprised of amyloid-β peptide (Aβ) and the presence of intraneuronal neurofibrillary tangles. However, a large body of evidence suggests that oxidative stress and inflammation are major contributors to the pathogenesis and progression of AD. To date, available pharmacologic treatments are only symptomatic. Clinical trials focused on amyloid and non-amyloid-targeted treatments with small molecule pharmacotherapy and immunotherapies have accumulated a long list of failures. Considering that around 90 % of the circulating Aβ is bound to albumin, and that a dynamic equilibrium exists between peripheral and central Aβ, plasma exchange with albumin replacement has emerged as a new approach in a multitargeted AD therapeutic strategy (AMBAR Program). In plasma exchange, a patient's plasma is removed by plasmapheresis to eliminate toxic endogenous substances, including Aβ and functionally impaired albumin. The fluid replacement used is therapeutic albumin, which acts not only as a plasma volume expander but also has numerous pleiotropic functions (e.g., circulating Aβ- binding capacity, transporter, detoxifier, antioxidant) that are clinically relevant for the treatment of AD. Positive results from the AMBAR Program (phase 1, 2, an 2b/3 trials), i.e., slower decline or stabilization of disease symptoms in the most relevant clinical efficacy and safety endpoints, offer a glimmer of hope to both AD patients and caregivers.
Topics: Albumins; Alzheimer Disease; Humans; Models, Molecular; Plasma Exchange
PubMed: 34083161
DOI: 10.1016/j.transci.2021.103164 -
Annals of Hepatology 2023
Topics: Humans; Liver Cirrhosis; Albumins; Treatment Outcome; Infusions, Intravenous
PubMed: 37659473
DOI: 10.1016/j.aohep.2023.101150 -
Neurologia (Barcelona, Spain) Sep 2016There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aβ) burden in... (Review)
Review
Treatment of Alzheimer disease using combination therapy with plasma exchange and haemapheresis with albumin and intravenous immunoglobulin: Rationale and treatment approach of the AMBAR (Alzheimer Management By Albumin Replacement) study.
INTRODUCTION
There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aβ) burden in the brain by sequestering plasma Aβ, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between Aβ and albumin that have given rise to AMBAR (Alzheimer's Disease Management by Albumin Replacement) project, a new multicentre, randomised, controlled clinical trial for the treatment of AD.
DEVELOPMENT
Results from preliminary research suggest that Albutein(®) (therapeutic albumin, Grifols) contains no quantifiable levels of Aβ. Studies also show that Albutein(®) has Aβ binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of Aβ that can induce albumin modification, thus affecting its biological functions. Results from the phase ii study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein(®) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of Aβ and cognitive improvement in treated patients. The AMBAR study will test combination therapy with therapeutic apheresis and haemopheresis with the possible leverage effect of Albutein(®) with intravenous immunoglobulin replacement (Flebogamma(®) DIF). Cognitive, functional, and behavioural changes in patients with mild to moderate AD will be assessed.
CONCLUSIONS
the AMBAR study represents a new therapeutic perspective for AD.
Topics: Aged; Aged, 80 and over; Albumins; Alzheimer Disease; Amyloid beta-Peptides; Humans; Immunoglobulins, Intravenous; Plasma Exchange; Plasmapheresis; Protein Binding
PubMed: 25023458
DOI: 10.1016/j.nrl.2014.02.003 -
American Journal of Physiology. Renal... Sep 2011There is increasing evidence that proteins in tubular fluid are "nephrotoxic." In vivo it is difficult to study protein loading of tubular epithelial cells in isolation,... (Comparative Study)
Comparative Study
There is increasing evidence that proteins in tubular fluid are "nephrotoxic." In vivo it is difficult to study protein loading of tubular epithelial cells in isolation, i.e., without concomitant glomerular damage or changes of renal hemodynamics, etc. Recently, a unique amphibian model has been described which takes advantage of the special anatomy of the amphibian kidney in which a subset of nephrons drains the peritoneal cavity (open nephrons) so that intraperitoneal injection of protein selectively causes protein storage in and peritubular fibrosis around open but not around closed tubules. There is an ongoing debate as to what degree albumin per se is nephrotoxic and whether modification of albumin alters its nephrotoxicity. We tested the hypothesis that carbamylation and glycation render albumin more nephrotoxic compared with native albumin and alternative albumin modifications, e.g., lipid oxidation and lipid depletion. Preparations of native and modified albumin were injected into the axolotl peritoneum. The kidneys were retrieved after 10 days and studied by light microscopy as well as by immunohistochemistry [transforming growth factor (TGF)-β, PDGF, NF-κB, collagen I and IV, RAGE], nonradioactive in situ hybridization, and Western blotting. Two investigators unaware of the animal groups evaluated and scored renal histology. Compared with unmodified albumin, glycated and carbamylated albumin caused more pronounced protein storage. After no more than 10 days, selective peritubular fibrosis was seen around nephrons draining the peritoneal cavity (open nephrons), but not around closed nephrons. Additionally, more intense expression of RAGE, NF-κB, as well as PDGF, TGF-β, EGF, ET-1, and others was noted by histochemistry and confirmed by RT-PCR for fibronectin and TGF-β as well as nonradioactive in situ hybridization for TGF-β and fibronectin. The data indicate that carbamylation and glycation increase the capacity of albumin to cause tubular cell damage and peritubular fibrosis.
Topics: Albumins; Ambystoma mexicanum; Animals; Carbamates; Fibrosis; Glycation End Products, Advanced; Injections, Intraperitoneal; Kidney; Models, Animal; NF-kappa B; Nephrons; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Serum Albumin; Transforming Growth Factor beta; Glycated Serum Albumin
PubMed: 21367923
DOI: 10.1152/ajprenal.00342.2010