Stable Plasma Protein Research Articles

Human Serum Albumin: A Novel Drug Delivery Carrier System

Serum albumin, often referred to simply as albumin, is a globular protein that in humans is encoded by the ALB gene. Albumin is a multifaceted, highly soluble, stable, nontoxic, non-poisonous, biocompatible and biodegradable plasma protein. Albumin has been widely studied as a protein carrier for drug delivery. Because of its versatile nature, it can also be used for the delivery of the hormones, metals and fatty acids by binding to its specific binding sites. Various studies revealed that albumin can be used to increase the circulating half-life and bioavailability of drug molecules which are smaller than the renal filtration threshold and are rapidly lost from the circulation leading to limiting therapeutic potential. This review article presents advantages, disadvantages, functions, importance, different nanoparticles that can be crowned with an albumin and the special features of albumin as a drug carrier, and how the understanding of these features is currently being employed to optimize the circulatory half-life albumin.

Integration of molecular profiles in a longitudinal wellness profiling cohort

An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.

Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population

Low-grade inflammation is thought to contribute to the development of cardiovascular disease (CVD), type-2 diabetes mellitus (T2D), cancer and mortality. Biomarkers of inflammation may aid in risk prediction and enable early intervention and prevention of disease. The aim of this study was to investigate whether plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) are predictive of disease and mortality in the general population. This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. General adult Caucasian population. The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. Blood samples were analysed for suPAR levels using a commercially available enzyme-linked immunosorbent assay. Risk of cancer (n = 308), CVD (n = 301), T2D (n = 59) and mortality (n = 411) was assessed with a multivariate proportional hazards model using Cox regression. Elevated baseline suPAR level was associated with an increased risk of cancer, CVD, T2D and mortality during follow-up. suPAR was more strongly associated with cancer, CVD and mortality in men than in women, and in younger compared with older individuals. suPAR remained significantly associated with the risk of negative outcome after adjustment for a number of relevant risk factors including C-reactive protein levels. Further validation in ethnic populations other than Caucasians is needed. The stable plasma protein suPAR may be a promising biomarker because of its independent association with incident cancer, CVD, T2D and mortality in the general population.

The Modulation of Transthyretin Tetramer Stability by Cysteine 10 Adducts and the Drug Diflunisal: DIRECT ANALYSIS BY FLUORESCENCE-DETECTED ANALYTICAL ULTRACENTRIFUGATION

Transthyretin (TTR) is normally a stable plasma protein. However, in cases of familial TTR-related amyloidosis and senile systemic amyloidosis (SSA), TTR is deposited as amyloid fibrils, leading to organ dysfunction and possibly death. The mechanism by which TTR undergoes the transition from stable, soluble precursor to insoluble amyloid fibril and the factors that promote this process are largely undetermined. Most models involve the dissociation of the native TTR tetramer as the initial step. It is largely accepted that the TTR gene mutations associated with TTR-related amyloidosis lead to the expression of variant proteins that are intrinsically unstable and prone to aggregation. It has been suggested that amyloidogenicity may be conferred to wild-type TTR (the form deposited in SSA) by chemical modification of the lone cysteine residue (Cys(10)) through mixed disulfide bonds. S-Sulfonation and S-cysteinylation are prevalent TTR modifications physiologically, and studies have suggested their ability to modulate the structure of TTR under denaturing conditions. In the present study, we have used fluorescence-detected sedimentation velocity to determine the effect of S-sulfonate and S-cysteine on the quaternary structural stability of fluorophore-conjugated recombinant TTR under nondenaturing conditions. We determined that S-sulfonation stabilized TTR tetramer stability by a factor of 7, whereas S-cysteinylation enhanced dissociation by 2-fold with respect to the unmodified form. In addition, we report the direct observation of tetramer stabilization by the potential therapeutic compound diflunisal. Finally, as proof of concept, we report the sedimentation of TTR in serum and the qualitative assessment of the resulting data.

Diabetic ketoacidosis and clozapine.

1 Ring J, Messmer K. Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet 1977;1:466-9. 2 Laxenaire MC, Charpentier C, Feldman L. [Anaphylactoid reactions to colloid plasma substitutes:...

The concomitant use of stable plasma protein solution (SPPS) should be avoided

The concomitant use of stable plasma protein solution (SPPS) should be avoided

Hypernatraemic dehydration after Lucozade

To emphasise the dangers of inappropriate rehydration fluids in the treatment of gastroenteritis. A two-year-old girl was admitted to hospital in shock and unconscious. She had a 36-hour history of diarrhoeal illness and had received Lucozade. Therapy with this hypertonic fluid resulted in worsening diarrhoea and seizures. On examination she had hypernatraemic dehydration and decorticate posturing. An intravenous line was inserted, stable plasma protein solution was given, and she was admitted to the intensive care unit. Anticonvulsant and antibiotic therapy were begun. Significant neurological impairment was still evident after 14 days, at which time shw was discharged from hospital. Six months later she had made a good recovery, with no persisting neurological deficit. The inappropriate use of hypertonic fluids in gastroenteritis may be associated with significant electrolyte imbalances and neurological sequelae.

Human albumin solutions: an audit of use in three major metropolitan hospitals: Subcommittee of the Victorian Drug Usage Advisory Committee

To evaluate the volume used and the indications for use of the human albumin solutions, stable plasma protein solution and normal serum albumin, in Victorian metropolitan teaching hospitals. The Victorian Drug Usage Advisory Committee conducted a prospective audit by means of a questionnaire in three major Melbourne teaching hospitals over a three-month period. All bottles of the human albumin solutions issued were numbered and a questionnaire regarding indications for use was completed for each patient treated with either product. The results were compared with the recommendations of the Australasian Society of Blood Transfusion to determine whether usage was appropriate, and the number of bottles used was analysed for each hospital and each major indication. The survey was comprehensive (84% of the forms were returned) and demonstrated that these products are used for appropriate clinical categories, for example, hypovolaemia, hypoalbuminaemia, and not for inappropriate indications, such as nutritional support or wound healing. There was however a marked variation in the level of usage for a given indication between the three hospitals. This variation reflected a considerable difference in unit policy regarding the use of these products in preference to crystalloid or synthetic colloid solutions. The variation suggests the need for more specific guidelines for the use of these products in defined clinical settings.

Possible Interaction between SPPS and Enalapril

A patient undergoing groin lymph node dissection with spinal and general anaesthesia was receiving enalapril to control hypertension. Infusion of stable plasma protein solution (Commonwealth Serum Laboratories, Australia) was associated with significant hypotension and flushing. A brief review of stable plasma protein solution and angiotensin converting enzyme inhibitor pharmacology is presented to provide a possible mechanism for these events. This mechanism implies that angiotensin converting enzyme inhibitor therapy is a relative contraindication to rapid SPPS infusion.

Stable plasma protein solution

Modern preparation methods reduce risk of untoward reactions

Temperature sensitivity within the pasteurization temperature range of prekallikrein activator in stable plasma protein solution (SPPS).

Human plasma protein fraction, used worldwide as a plasma expander, produces in some recipients adverse reactions resembling those following infusion of bradykinin. The presence of excessive quantities of a Hageman factor degradation product (prekallikrein activator, PKA) in the protein solution is thought to be the reason for these reactions. Like other manufacturers, CSL has experienced batch‐to‐batch variability in the PKA levels in its plasma protein product (SPPS). In this paper, data is presented showing that PKA is inactivated to a greater extent at the high extreme (60.5 C) of the pasteurization temperature range than at the low extreme (59.5 C). This difference in pasteurization temperature can lead to a two‐ or threefold difference in PKA concentration in the final product and can make the difference between the product being potentially reactive or innocuous, as well as accounting for some of the batch‐to‐batch variability observed in the past.

Inhibition of the hypotensive effect of plasma protein solutions by C1esterase inhibitor

The hypotensive effect of stable plasma protein solution (SPPS) is a well-known phenomenon, causing serious problems in surgical patients and patients supported by cardiopulmonary bypass. Kinins are believed to be responsible. A study was made to prevent this hypotension by adding C1 esterase inhibitor to the SPPS and comparing this with 5% human albumin. The results shows a significant difference between the effects of SPPS and SPPS plus C1 esterase inhibitor infusion on bypass. Five percent human albumin did not cause hypotension. Possible sequelae are discussed.

Venoconstrictor activity of some precursor fractions of stable plasma protein solution.

Stable plasma protein solution (SPPS) is a 5% solution of human plasma albumin and some globulins. Rapid infusion of some batches of SPPS and analogous solutions prepared by similar processes induce paradoxical hypotensive reactions. In the current experiments, a number of precursor fractions of a single batch of SPPS were examined for kininogen content and for venoconstrictor activity on the isolated central vein of the rabbit ear. Unheated SPPS contained both venoconstrictor activity and kininogen. Among the various precursor fractions examined, Cohn fraction II + III (a precursor of fraction III-0) contained the greatest venoconstrictor activity. There was no evidence of kininogen depletion during the stages of fractionation examined but some generation of venoconstrictor material. Column chromatography suggested a molecular weight of approximately 1,500 for the major active material in unheated SPPS. It appears possible that the 14-amino acid hypotensive peptide present in fraction III-0 may also be present in SPPS, where it may contribute to the hypotensive effects of this solution.

Mechanisms of vasomotor reactions in the use of SPPS.

Vasomotor reactions have been reported during infusions of stable plasma protein solutions (SPPS). Possible mechanisms of this phenomenon have been studied using rabbit ear vein preparations. Most samples of SPPS were found inactive but could be activated by proteolytic enzymes. Two factors appear to be responsible: one has kinin-like properties and the other behaves as kininogen. The latter could be activated by proteases released from both granulocytes and platelets and it is suggested that such activation may occur in clinical use. The bioassay employed in this study provides a basis for modifications in production of SPPS to eliminate these factors.

Serum amyloid P-component is an acute-phase reactant in the mouse

THE acute-phase reaction in mammals is characterised by an increase in the concentration of certain plasma proteins which starts within hours or days of most forms of acute tissue damage or inflammation, and persists with chronic inflammation and malignant neoplasia1–4. Among acute-phase reactants are protease inhibitors, coagulation factors, complement components and transport proteins as well as proteins without known in vivo roles, such as the classical reactant, C-reactive protein (CRP)1–4. The pathophysiological significance of the acute-phase reaction is not known, but it is a usual accompaniment of tissue damage, and it is of clinical value in the assessment of disease activity4. We now report that in the mouse, serum amyloid P-component (protein SAP)5, which is a stable plasma protein in man6, is a major acute-phase reactant. In addition, our observations facilitate investigation of the function of protein SAP and of the pathogenesis of amyloidosis, which is a serious disease in man.

Mechanisms of Vasomotor Reactions in the Use of SPPS

Vasomotor reactions have been reported during infusions of stable plasma protein solutions (SPPS). Possible mechanisms of this phenomenon have been studied using rabbit ear vein preparations. Most samples of SPPS were found inactive but could be activated by proteolytic enzymes. Two factors appear to be responsible: one has kinin-like properties and the other behaves as kininogen. The latter could be activated by proteases released from both granulocytes and platelets and it is suggested that such activation may occur in clinical use. The bioassay employed in this study provides a basis for modifications in production of SPPS to eliminate these factors.

Reactions to Rapid Infusion of Stable Plasma Protein Solution during Large Volume Plasma Exchange

Five per cent heat treated stable plasma protein solution (SPPS) has been rapidly infused into 25 patients, as fluid replacement during large volume plasmapheresis. Reactions were produced in 20 patients. Subjective symptoms of flushing, nasal stuffiness, fullness and throbbing in the head, colicky abdominal pain, metallic taste or apprehension were observed in 16 patients, and 11 patients became hypotensive with an average systolic pressure of 70 mm Hg. These observations support earlier reports of hypotension due to rapid SPPS infusion, and document the occurrence of subjective symptoms which may be the harbingers of a hypotensive reaction. In view of the known presence of a bradykinin-like substance in some heat treated plasma protein solutions, hypotension during SPPS infusion should be interpreted with caution in the light of these findings.

A comparison of cryoprecipitated plasma and albumin solutions for machine preservation of ischaemically damaged canine kidneys.

Four solutions for machine perfusion and preservation of is chœmically damaged canine kidneys were compared. They were (i) canine Cryoprecipitated plasma, (ii) canine albumin, (iii) human stable plasma protein, and (iv) human albumin. The results with both canine protein solutions were satisfactory. The solutions containing human protein were found unsuitable for canine kidney preservation. It was concluded that albumin solutions were at least as effective as cryoprecipitate for 24-hour perfusion of ischœmically damaged canine kidneys.

Comparative Effects of Dextrans, Gelatin and Stable Plasma Protein Solution (SPPS) on the Experimental Disseminated Intravascular Coagulation (DIC)

In an experimental study on the rabbit (80 animals) the haemostasis changes observed during the perfusion of dextrans of various molecular weights, gelatin and stable plasma protein solution (1.5 g/kg/h during 3 h) are compared using the normal animal and the animal with DIC induced by thrombin perfusion (100 U/kg/h during 3 h). With the normal animal, no significant disorders of haemostasis have been observed during perfusion of dextran 40 or SPPS. On the contrary, the perfusions with dextran 75 or gelatin are associated with modifications of platelet activities and of platelet and plasma plasmininhibiting activities similar to those found in thrombophilia states. Perfusion with dextran 200 produces haemostasis changes similar to those found during consumptive coagulopathies. In the animals with DIC, preventive, simultaneous or curative administration of dextrans 40, 75, 200 or gelatin significantly enhances the haemostasis disorders produced by perfusion with thrombin alone, this is opposed to SPPS which has no influence.

Hypotensive effects of stable plasma protein solution (SPPS): a preliminary communication.

Medical Journal of AustraliaVolume 2, Issue 25 p. 1308-1309 Correspondence HYPOTENSIVE EFFECTS OF STABLE PLASMA PROTEIN SOLUTION (SPPS): A PRELIMINARY COMMUNICATION First published: 01 December 1971 https://doi.org/10.5694/j.1326-5377.1971.tb92856.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume2, Issue25December 1971Pages 1308-1309 RelatedInformation