Use Of Human Serum Albumin Research Articles

Prescribers’ Compliance to Human Serum Albumin Usage Criteria and Its Implication on Cost Saving

Human serum albumin (HSA) is a commonly used product with high impact on healthcare expenditure. Little is known regarding the appropriateness of HSA use in healthcare system. This study aimed to assess prescriber’s compliance to the approved HSA criteria. Potential cost saving was also estimated. A cross-sectional study was performed in a tertiary care, university hospital in Bangkok in 2019. Prescriptions for HSA for all adult patients along with corresponding medical records were reviewed and assessed against the approved HSA criteria. Deviation from the criteria was used to estimate the potential cost saving. A total of 688 prescriptions were reviewed, 200 prescriptions met the inclusion criteria and were included in the analysis. Among six indications in the approved criteria for HSA, the rates of criteria compliance ranged from 48 to 90%. Hypoalbuminemia was found to be the main reason for inappropriate use. The estimated cost saving from inappropriate HSA use was €3,543 (€59 per prescription). Significant deviation from the approved criteria of HSA use was seen in a Thai hospital and significant cost saving can be made by increasing the compliance to the criteria. A practice improvement initiative to promote rational use of HSA is warranted.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

A review of Zenalb 20 with the focus on its application in the clinical setting for patients requiring low sodium or chloride albumin

Abstract Objectives Perceptions that formulations of human albumin solution have not evolved and are interchangeable need to be reconsidered amid renewed appreciation of this therapy in its current uses, and in potential new uses. Initially indicated for volume expansion in severely ill or trauma patients, human albumin solution has been established in a broadening array of clinical applications as understanding of its structure–function relationships has deepened. This article reviews the clinical roles of human albumin solution, the evolution of manufacturing processes and the growing interest in the use of albumin as a therapeutic agent in an expanding range of clinical scenarios. Methods Literature searching was conducted through PubMed, bibliographies of prior publications specific to human albumin solution and ClinicalTrials.gov. This review includes multidisciplinary perspectives on the chemistry, physiology, extraction, processing, formulation and clinical applications of human albumin based on the published literature, authors’ professional experience and product quality-assurance data. Key findings Current formulations of human albumin solution vary in composition, including the use of chemical stabilizers and concentrations of key electrolytes, especially sodium and chloride. Through innovations in manufacturing processes since the 1990s, Zenalb 20 is defined by its high albumin purity, use of a single stabilizer and electrolyte concentrations that are substantially lower than in normal human plasma. The clinical relevance of these features may increase as the use of human serum albumin continues to expand in patient populations receiving multiple medications and fluids, for whom electrolyte balance is crucial. Conclusion As a low electrolyte formulation, Zenalb 20 provides a clinical option to increase oncotic pressure when a colloid is needed without worsening pathological hypernatraemia, hyperchloraemia and hyperkalaemia.

Successful Use of Mycophenolate Mofetil as Adjunct to Prednisolone for Treatment of Acute Kidney Injury Secondary to Human Serum Albumin Administration in a Dog.

The use of human serum albumin (HSA) is described in dogs receiving critical care. However, despite the high degree of homology, anaphylactic and delayed hypersensitivity reactions are reported. Delayed type III hypersensitivity reactions can lead to glomerulonephritis and acute kidney injury (AKI). Undiluted 20% HSA was administered to a 4.8 yr old intact male Labrador Retriever with severe hypoalbuminemia, following surgical management of septic peritonitis of gastrointestinal origin. Nineteen days after HSA administration, the dog developed peracute high magnitude renal proteinuria and AKI. Rapid immunosuppression, using a combination of prednisolone and mycophenolate mofetil, resulted in full resolution of AKI, hypoalbuminemia, and proteinuria. Addition of mycophenolate mofetil may have resulted in the first documented case of full renal recovery from hypersensitivity-induced AKI caused by HSA administration.

Blood, sweat, and tears: extraterrestrial regolith biocomposites with in vivo binders.

The proverbial phrase ‘you can’t get blood from a stone’ is used to describe a task that is practically impossible regardless of how much force or effort is exerted. This phrase is well-suited to humanity’s first crewed mission to Mars, which will likely be the most difficult and technologically challenging human endeavor ever undertaken. The high cost and significant time delay associated with delivering payloads to the Martian surface means that exploitation of resources in situ — including inorganic rock and dust (regolith), water deposits, and atmospheric gases — will be an important part of any crewed mission to the Red Planet. Yet there is one significant, but chronically overlooked, source of natural resources that will — by definition — also be available on any crewed mission to Mars: the crew themselves. In this work, we explore the use of human serum albumin (HSA) — a common protein obtained from blood plasma — as a binder for simulated Lunar and Martian regolith to produce so-called ‘extraterrestrial regolith biocomposites (ERBs).’ In essence, HSA produced by astronauts in vivo could be extracted on a semi-continuous basis and combined with Lunar or Martian regolith to ‘get stone from blood’, to rephrase the proverb. Employing a simple fabrication strategy, HSA-based ERBs were produced and displayed compressive strengths as high as 25.0 MPa. For comparison, standard concrete typically has a compressive strength ranging between 20 and 32 MPa. The incorporation of urea — which could be extracted from the urine, sweat, or tears of astronauts — could further increase the compressive strength by over 300% in some instances, with the best-performing formulation having an average compressive strength of 39.7 MPa. Furthermore, we demonstrate that HSA-ERBs have the potential to be 3D-printed, opening up an interesting potential avenue for extraterrestrial construction using human-derived feedstocks. The mechanism of adhesion was investigated and attributed to the dehydration-induced reorganization of the protein secondary structure into a densely hydrogen-bonded, supramolecular β-sheet network — analogous to the cohesion mechanism of spider silk. For comparison, synthetic spider silk and bovine serum albumin (BSA) were also investigated as regolith binders — which could also feasibly be produced on a Martian colony with future advancements in biomanufacturing technology.

Expert consensus on the use of human serum albumin in critically ill patients.

Expert consensus on the use of human serum albumin in critically ill patients.

Albumin, as a Therapeutic Protein: Potential Source, Application, Isolation and Purification

Albumin is one of the plasma proteins found in the human body, which is about 55-60%, and the total normal serum protein level is 3.8-5.0 g/dL. Albumin consists of a single chain of a polypeptide with a molecular weight of 66.5kDa and consists of 585 amino acids. In the albumin molecule, 17 disulfide bonds connect amino acids containing sulfur. The molecular albumin is elliptical so that with such molecular forms, it will not increase the plasma viscosity and dissolve perfectly. Albumin is protein and its action as a transport agent and maintains colloid osmotic pressure. The need for albumin in the world reaches 500 tons annually, which is used hypoalbuminemia therapy. Hypoalbuminemia therapy which is often used is HSA (Human Serum Albumin) therapy. The use of HSA has disadvantages such as causing infections, expensive processing costs, and the cost of products. Thus other sources of albumin are needed. One that can be the potential source of albumin is Indonesian catfish (Clariasgariepinus). Our research studies have obtained the albumin from Indonesian catfish (C. gariepinus) and Patin fish (Pangasianodon hypophthalmus) with high yield and purity. The Indonesian catfish is the potential albumin source after the isolation and purification process was obtained that the molecular weight, the purity, and the total albumin content of purified albumin were 66.7 kDa, 95.38%, and 118.5 mg /g of wet weight, respectively.

Single-center analysis of the inappropriate use of human albumin and nutritional support in hospitalized patients with hypoproteinemia in China.

BackgroundThis study used single-center analysis of human serum albumin clinical usage and enteral-parenteral nutritional support to establish clinical application standards for the rational use of human serum albumin.MethodsA total of 1984 patients receiving human serum albumin were enrolled in this retrospective study to analyze the rational application of human serum albumin and enteral-parenteral nutritional support.ResultsAmong 1984 patients, 1044 (52.6%) were found to have irrational applications for human serum albumin use. Major indications for irrational applications were hypoproteinemia (30.0%) and nutritional support (21.9%). Surgical departments including thoracic surgery, orthopedics, and neurosurgery had the most irrational applications, occupying 18.4%, 8.4%, and 4.2%, respectively. A total of 1627 patients (82%) required nutritional support and 745 (45.8%) had irrational nutritional support. Moreover, 694 patients (35.0%) received human serum albumin as the only source of nutritional support.ConclusionsClinical training and the establishment of an approval system should be used to enhance the rational use of human serum albumin, ensuring medication safety, reducing medical costs, and avoiding the waste of medical resources.

The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug.

The interaction of temozolomide (TMZ) (the main chemotherapeutic agent for brain tumors) with blood components has not been studied at the molecular level to date, even though such information is essential in the design of dosage forms for optimal therapy. This work explores the binding of TMZ to human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), as well as to blood cell-mimicking membrane systems. Absorption and fluorescence experiments with model membranes indicate that TMZ does not penetrate into the lipid bilayer, but binds to the membrane surface with very low affinity. Fluorescence experiments performed with the plasma proteins suggest that in human plasma, most of the bound TMZ is attached to HSA rather than to AGP. This interaction is moderate and likely mediated by hydrogen-bonding and hydrophobic forces, which increase the hydrolytic stability of the drug. These experiments are supported by docking and molecular dynamics simulations, which reveal that TMZ is mainly inserted in the subdomain IIA of HSA, establishing π-stacking interactions with the tryptophan residue. Considering the overexpression of albumin receptors in tumor cells, our results propose that part of the administered TMZ may reach its target bound to plasma albumin and suggest that HSA-based nanocarriers are suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to tumor cells.

Human serum albumin presents isoform variants with altered neonatal Fc receptor interactions.

Human serum albumin (HSA) is the most abundant protein in plasma and presents the particularity, with IgG, to have an extraordinary long serum half-life conferred by its interaction with the neonatal Fc receptor (FcRn). If the impact of IgG post-translational modifications (PTMs) on FcRn binding is well documented, it is far less reported for HSA despite numerous PTMs occurring on the protein in plasma. HSA is susceptible to numerous degradation reactions in plasma, because of aging, oxidative stress or liver and pancreas related pathologies. In the present study, we combined FcRn affinity chromatography and mass spectrometry to investigate the impact of HSA PTMs upon FcRn binding. This methodology presents the advantage to distinguish the effect of a single modification from a plasma HSA preparation made of a mixture of different isoforms. Cys34 oxidation, Lys525 glycation, and Leu585 C-terminal truncation, which are modifications related to several pathological conditions, were demonstrated to act negatively on HSA-FcRn interaction. The HSA-FcRn binding alteration generated by these modifications is consistent with their vicinity with the interaction interface of the two proteins. Results were discussed regarding altered half-life of HSA observed in several disease states and pave the way toward new understandings of the hypoalbuminemia pathogenesis. SIGNIFICANCE STATEMENT: In this study, we investigated the impact of several post-translational modifications of HSA toward its ability to bind to the neonatal Fc receptor using in vitro affinity chromatography, mass spectrometry, and surface plasmon resonance. Cys34 oxidation, Lys525 glycation, and Leu585 C-terminal truncation were demonstrated to decrease HSA-FcRn binding. These modifications occurring in circulating HSA were discussed in relation to several pathologies as well as for the use of HSA as a therapeutic protein.

Efficacy of an Intravenous Form of Rifapentine in a Model of Experimental Tuberculosis in Mice

Solubilization of rifapentine with human serum albumin (HSA) was used to produce a water-miscible form consisting of a colloidal suspension of particles of size 538 ± 9 nm. Dilution of the suspension more than 20-fold led to dissociation of the aggregates formed during solubilization procedure, producing a transparent solution. This was associated with a reduction in particle size to 10 – 20 nm, corresponding to the particle size in HSA solution at the same concentration. A fluorescence method showed that suspensions contained both free rifapentine and its complex with HSA. Studies of the activity against the pathogen of tuberculosis, Mycobacterium tuberculosis H37Rv, in a model of acute infection in Balb/c mice showed that the water-miscible form of rifapentine given intravenously had high activity against mycobacteria, comparable with the activity of rifapentine substance, decreasing mycobacterial loadings in the parenchymatous organs from 106 – 107 to 102 – 103 cfu/organ. Thus, use of HSA as solubilizer yielded an intravenous form of rifapentine retaining the activity of the antibiotic against Mycobacterium tuberculosis.

Human serum albumin-mediated apoptin delivery suppresses breast cancer cell growth in vitro and in vivo.

Gene therapy is one of the most promising potential therapeutic strategies for many types of cancer. Cell apoptosis is an active, programmed physiological process of the body, and its disruption has been closely associated with the occurrence of tumor development. Apoptin is known to induce tumor cell apoptosis. In the present study, the MCF-7 breast cancer cell line was transfected with a human serum albumin (HSA) and apoptin expressing plasmid [HSA-polyethylenimine (PEI)-pcDNA-Apoptin]. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to detect the expression of apoptin in the transfected MCF-7 cells, while MTT assays and flow cytometry were conducted to detect cell viability and apoptosis. Furthermore, hematoxylin and eosin staining was used to observe the morphology of xenografts from mice injected with MCF-7 cells. It was demonstrated that the HSA-PEI-pcDNA-Apoptin expression plasmid resulted in the upregulation of apoptin in MCF-7 cells, and efficiently suppressed breast tumor growth in vivo. These findings indicated that the use of HSA as an apoptin expression vector has potential therapeutic benefits for cancer and confirms the requirement for the further evaluation of apoptin in clinical trials.

Human serum albumin as vehicle for the solubilization of perylene diimides in aqueous solutions

The chemical, physical and photophysical properties of perylene diimides have attracted substantial attention for the potential applications in diverse fields ranging from advanced materials to biomedical applications. Some applications require the diimides to be in aqueous environment where they tend to dissolve poorly. We investigated the use of human serum albumin as a vehicle to increase the aqueous exposure of monomeric perylene diimides. Since studies on the interactions of these compounds with protein is scarce we characterized the binding and the possible effects on the protein. In order to increase the affinity of the dyes to the protein we have used perylene diimides with substituents that replicate the side chains of natural amino acids. The results show that only the dyes containing the side chain of leucine and phenylalanine yield measurable binding. Only the phenylalanine analogue promotes energy transfer with the lone tryptophan residue of albumin indicating different binding modalities for the dyes. In addition, this analogue is the only one which shows photochemical activity that prompts its release from the protein upon laser irradiation.

Allergen stability of testing/treatment boards and immunotherapy vials with various diluents.

Otolaryngologists commonly use glycerin and normal saline with phenol (NSP) in diluting solutions to help preserve allergenicity in immunotherapy vials. Studies have shown that diluting with human serum albumin (HSA) may provide better allergen stability. The purpose of this study was to assess the ability of various diluents to preserve allergen content in testing/treatment boards (TTBs) and immunotherapy treatment vials (ITVs) at multiple time points. TTBs with 4 allergens were prepared with HSA, NSP, 10% glycerin, and 50% glycerin. The major allergen content of the TTBs was measured at creation (time 0), 3 days, 8 weeks, and 18 weeks. Multiallergen ITVs containing the 4 allergens were prepared from the NSP board (diluted to 10% glycerin) and the HSA board (diluted in HSA) at the time of making the freshly prepared TTBs and again 8 weeks later, simulating the creation of ITVs from a "new" and an "old" TTB. The major allergen content of these ITVs was determined at creation and at interval time points thereafter. TTBs and ITVs showed a substantial loss of allergen at day 3. The loss of allergen was more pronounced in the more dilute (#4, #5, and #6) vials. HSA and 50% glycerin showed superior allergen preservation compared to NSP and 10% glycerin in TTBs. HSA showed superior allergen preservation compared to 10% glycerin-NSP in ITVs. The use of HSA as a diluent in TTBs and ITVs showed superior allergen preservation compared to NSP and 10% glycerin, particularly for more dilute vials.

A Device for Albumin and Cytosol Detoxication

A new detoxication method based the Bioartificial Liver apparatus and the use of human serum albumin (HSA) and porcine hepatocyte cytosol (PHC) is described. The method is based on the interaction of HSA and PHC with the patient’s blood through a semi-permeable membrane. The apparatus consists of a bioreactor, hemodialyzer, and blood line as well as thermoregulation, oxygenation, and procedure safety systems. The PHC and HSA dialyzing media were tested using the Bioartificial Liver apparatus. They appeared to be highly effective and capable of reducing biochemical markers of cytolysis, cholestasis, and endogenous intoxication in patients without any adverse side effects. Thus, the method can be recommended for further clinical tests and introduction into intensive care practice.

Review of the rational use and adverse reactions to human serum albumin in the People’s Republic of China

Human serum albumin (HSA) is an ideal natural colloid that has been widely used in clinical practice for supplemental albumin or as a plasma substitute during therapeutic plasma exchanges to redress hypoproteinemia. However, a paucity of well-designed clinical trials, a lack of a clear cut survival benefit, and frequent case reports of adverse drug reaction (ADR) make the use of HSA controversial. This study aims to review and to comment on the reported ADRs of HSA in the People’s Republic of China, so as to provide the basis for rational HSA use in clinical settings. Data on the ADR case reports from HSA administration between January 1990 and December 2012 available from the China National Knowledge Infrastructure (CNKI) database, Wanfang data (WF), and Chinese Biomedical Literature (CBM) were reviewed. The reasons for using HSA, the types of ADRs, the causality of ADRs and the rationality for HSA administration were extracted and analyzed. In total, 61 cases of ADR reports were identified of which the primary disease of patients using HSA was malignant tumor (34.42%). The primary ADR was anaphylaxis (59.02%). Of the 61 cases, 30 were caused by irrational use of HSA. The most common irrational use was off-label use (56.67%), followed by inappropriate infusion rate. Therefore, we conclude that to avoid the occurrence of ADRs, guidelines for using HSA are needed to guarantee its rational use and HSA should be used strictly according to these guidelines. In addition, medical staff, including clinical pharmacists and nurses, should pay more attention to the patients who inject HSA to ensure its safe use in the clinic.

Study of the Enantioselective Interaction of Diclofop and Human Serum Albumin by Spectroscopic and Molecular Modeling Approaches In Vitro

In this contribution, the enantioselective interactions between diclofop (DC) and human serum albumin (HSA) were explored by steady-state and 3D fluorescence, ultraviolet-visible spectroscopy (UV-vis), and molecular modeling. The binding constants between R-DC and HSA were 0.9213 × 10(5), 0.9118 × 10(5), and 0.9009 × 10(5) L · mol(-1) at 293, 303, 313 K, respectively. Moreover, the binding constants of S-DC for HSA were 1.4766 × 10(5), 1.2899 × 10(5), and 1.0882 × 10(5) L · mol(-1) at 293, 303, and 313 K individually. Such consequences markedly implied the binding between DC enantiomers and HSA were enantioselective with higher affinity for S-DC. Steady-state fluorescence study evidenced the formation of DC-HSA complex and there was a single class of binding site on HSA. The thermodynamic parameters (ΔH, ΔS, ΔG) of the reaction clearly indicated that hydrophobic effects and H-bonds contribute to the formation of DC-HSA complex, which was in excellent agreement with molecular simulations. In addition, both site-competitive replacement and molecular modeling suggested that DC enantiomers were located within the binding pocket of Sudlow's site II. Furthermore, the alterations of HSA secondary structure in the presence of DC enantiomers were verified by UV-vis absorption and 3D fluorescence spectroscopy. This study can provide important insight into the enantioselective interaction of physiological protein HSA with chiral aryloxyphenoxy propionate herbicides and gives support to the use of HSA for chiral pesticides ecotoxicology and environmental risk assessment.

Supplements in Human Islet Culture: Human Serum Albumin is Inferior to Fetal Bovine Serum

Culture of human islets before clinical transplantation or distribution for research purposes is standard practice. At the time the Edmonton protocol was introduced, clinical islet manufacturing did not include culture, and human serum albumin (HSA), instead of fetal bovine serum (FBS), was used during other steps of the process to avoid the introduction of xenogeneic material. When culture was subsequently introduced, HSA was also used for medium supplementation instead of FBS, which was typically used for research islet culture. The use of HSA as culture supplement was not evaluated before this implementation. We performed a retrospective analysis of 103 high-purity islet preparations (76 research preparations, all with FBS culture supplementation, and 27 clinical preparations, all with HSA supplementation) for oxygen consumption rate per DNA content (OCR/DNA; a measure of viability) and diabetes reversal rate in diabetic nude mice (a measure of potency). After 2-day culture, research preparations exhibited an average OCR/DNA 51% higher (p < 0.001) and an average diabetes reversal rate 54% higher (p < 0.05) than clinical preparations, despite 87% of the research islet preparations having been derived from research-grade pancreata that are considered of lower quality. In a prospective paired study on islets from eight research preparations, OCR/DNA was, on average, 27% higher with FBS supplementation than that with HSA supplementation (p < 0.05). We conclude that the quality of clinical islet preparations can be improved when culture is performed in media supplemented with serum instead of albumin.

Human serum albumin-coated gold nanoparticles for selective extraction of lysozyme from real-world samples prior to capillary electrophoresis

This study describes the use of human serum albumin (HSA)-modified gold nanoparticles (HSA-AuNPs) for the selective extraction and enrichment of high-pI protein, lysozyme (Lyz) prior to analysis by capillary electrophoresis (CE) with UV detection. HSA-AuNPs are capable of extracting Lyz from a complex matrix because a HSA capping layer not only stabilizes gold nanoparticles in a high-salt environment but also exhibits strong electrostatic attraction with Lyz under neutral pH condition. Efficient separation of Lyz and other high-pI proteins has been successfully achieved by the filling of cationic polyelectrolyte, poly(diallydimethylammonium chloride) (PDDAC), to the background electrolyte. After capturing Lyz with HSA-AuNPs, PDDAC-filled CE can be directly used for the analysis of the extracted Lyz without the addition of the releasing agent into the extractor. The extraction efficiency relied on the pH of the solution and the concentration of HSA-AuNPs. Under optimal extraction conditions, the limit of detection at a signal-to-noise ratio of 3 for Lyz was down to 8nM. The combination of HSA-AuNP extraction and PDDAC-filled CE has been applied the analyses of Lyz in hen egg white, human milk, and human tear. Also, this NP-based extraction can be coupled to matrix-assisted desorption/ionization time-of-flight mass spectrometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Human Serum Albumin-modified Fe3O4 Magnetic Nanoparticles for Affinity-SALDI-MS of Small-Molecule Drugs in Biological Liquids

Here, we report on the use of human serum albumin (HSA)-modified Fe(3)O(4) nanoparticles (NPs) (HSA-Fe(3)O(4) NPs) for affinity-SALDI-MS of small drugs in human biological liquids. We demonstrated that HSA-Fe(3)O(4) NPs effectively captured small drugs from human urine and serum via the interactions between HSA and these drugs. The drugs adsorbed on HSA could then be identified by directly introducing the HSA-Fe(3)O(4) NPs into a mass spectrometer for SALDI-MS analysis. The ability of HSA to interact with multiple small drugs facilitated the simultaneous detection of a 4-drug-mixture in serum, viz., phenytoin, ibuprofen, camptothecin, and warfarin sodium, by affinity-SALDI-MS using HSA-Fe(3)O(4) NPs. In contrast, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) with an organic matrix could detect only warfarin sodium. We also demonstrated the capacity of affinity-SALDI-MS to quantify warfarin sodium in urine samples across a range of 50 - 1000 μM (R(2) = 0.998) when using HSA-Fe(3)O(4) NPs. The detection sensitivity was further improved to a range of 5 - 100 μM (R(2) = 0.999) by using denatured HSA. The open structure of denatured HSA may enhance the effective extraction of small drugs from biological liquids, and increase the detection-sensitivity of affinity-SALDI-MS. Affinity-SALDI-MS using protein-modified Fe(3)O(4) NPs can open up new approaches to the analytical detection of small drugs in biological liquids by SALDI-MS.