Assessment of arsenic distribution, bioaccessibility and speciation in rice utilizing continuous extraction and in vitro digestion.

Rice, a staple food for half the world's population, easily accumulates arsenic (As). Research on As distribution in rice protein and starch and its relationship with rice As bioaccessibility remains limited. This study investigated As distribution, chemical composition, As bioaccessibility and speciation in rice by continuous extraction and in vitro digestion. Of the total As, 87.5-94.5% was in rice protein and 5.0-9.8% in rice starch. The As amount in different protein fractions decreased as follows: glutelin > globulin > albumin > prolamin. As(V), As(III) and DMA in rice were more bioaccessible in the small intestinal phase than the gastric phase, and almost all As(V) dissolved in the small intestinal phase. Bioaccessible As in gastrointestinal digestive solution and As mass in protein fractions (albumin, globulin, and glutelin) were significantly positively correlated (p < 0.05). These results illuminate the bioaccessibility of As to humans consuming As-contaminated rice and avoid overassessment.

Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer.

Blood transport proteins are biogenic molecules with unique and interesting inherent characteristics that make up living organisms. As the utilization of their inherent characteristics can be a groundbreaking strategy to resolve and improve several clinical problems, attempts have been made to develop pharmaceutical and biomedical preparations based on blood transport proteins for the treatment and diagnosis of disorders. Among various blood transport proteins, we focus on the immense potential of hemoglobin and albumin to serve as carriers of biomedical gases (oxygen and carbon monoxide) and anticancer agents (low-molecular compounds and antisense oligodeoxynucleotides), respectively, for the development of innovative drug delivery systems (DDS) to treat intractable disorders and solid cancers. In this review, I introduce the pharmaceutical technology, strategies, and application of DDS carriers that have been designed on the basis of the structure and function of hemoglobin and albumin. In addition, the prospect of using hemoglobin and albumin as materials for DDS carriers is discussed.

A Two-Step Immunocapture LC/MS/MS Assay for Plasma Stability and Payload Migration Assessment of Cysteine-Maleimide-Based Antibody Drug Conjugates.

Plasma stability assessment under physiological temperature is an essential step for developing and optimizing antibody drug conjugate (ADC) molecules, especially those with cleavable linkers. The assessment of plasma stability often requires monitoring multiple analytes using a combination of bioanalytical assays for free payloads, conjugated payloads (or conjugated antibodies), total antibodies, and payloads that have migrated from antibodies to plasma constituent proteins. Bioanalytical assays are needed in early drug discovery to quickly screen diverse ADC candidates of different antibody constructs, linker variants, and antibody anchor sites. To improve the sensitivity and selectivity of LC/MS/MS-based assays for the assessment, immunocapture has been widely used for extracting ADCs and unconjugated antibodies from plasma samples. In this study, a novel two-step immunocapture LC/MS/MS assay was described to allow the quantification of conjugated payloads, total antibodies, and migrated payloads forming adducts with albumin in the plasma samples for stability assessment. A target antigen immobilized on magnetic beads was used to exhaustively extract the ADC and antibody-associated species. The remaining supernatant was then extracted further with anti-albumin beads for recovering the albumin-associated adducts for quantification. The method was optimized for higher efficiency and cost-effectiveness using microwave enhanced papain-based enzymatic cleavage for measuring conjugated payloads of ADCs and lysyl endopeptidase cleavage in the total antibody assay. A maleimide linker-based ADC with a proprietary payload, TAK-001, was used to demonstrate the streamlined workflow of the ADC stability assessment. The method could provide valuable evaluation of the stability of the ADC as well as the quantitative assessment of the albumin adducts formed from the linker-payload migration in mouse and human plasma. Furthermore, the method should be readily adaptable for other ADCs using thiol-maleimide conjugation chemistry.

Albumin-Assisted Method Allows Assessment of Release of Hydrophobic Drugs From Nanocarriers.

Polymeric nanoparticles have been extensively studied as drug delivery vehicles both in vitro and in vivo for the last two decades. In vitro methods to assess drug release profiles usually utilize degradation of nanoparticles in aqueous medium, followed by the measurement of the concentration of the released drug. This method, however, is difficult to use for drugs that are poorly water soluble. In this study, a protocol for measuring drug release kinetic using albumin solution as the medium is described. Albumin is a major blood transport protein, which mediates transport of many lipid soluble compounds including fatty acids, hormones, and bilirubin. The use of a dialysis-based system utilizing albumin dialysate solution allows hydrophobic drug release from a diverse set of drug delivery modalities is demonstrated. The method using liposomes and PLGA nanoparticles as drug carriers, and two model hydrophobic drugs, 17ß-estradiol, and dexamethasone is validated.

Quantitative assessment of liver function with whole-liver T1rho mapping at 3.0T.

OBJECTIVES: To assess the segmental liver function in healthy subjects and liver cirrhosis (LC) patients with different Child-Pugh grades using whole-liver T1rho mapping at 3.0T. METHODS: Thirty-three healthy volunteers and 33 patients with clinically diagnosed LC were examined using a three-dimensional (3D) whole-liver coverage T1rho mapping. T1rho maps were calculated from five respiratory-triggered sequences with different spin-lock durations (0, 10, 20, 40, and 60ms). The patients were classified into group A with Child-Pugh A cirrhosis and group B with Child-Pugh B or C cirrhosis. The hepatic T1rho values in different segments of the healthy volunteers and LC patients were compared, and receiver operating characteristic curves (ROC) were plotted to determine the performance of T1rho. RESULTS: The median T1rho value of the patients (Child-Pugh class A: 47.07ms; Child-Pugh classes B and C: 51.09ms) was significantly higher than that of the healthy volunteers (39.37ms, P<0.001). No remarkable variations among different hepatic segments in LC patients with various Child-Pugh grades were found (P>0.05). The T1rho values of the liver parenchyma were significantly correlated with albumin (r=-0.590, P<0.001) and prothrombin time (r=0.601, P<0.001). The T1rho values in patients increased with an increase in the Child-Pugh classification (r=0.574, P<0.001). CONCLUSIONS: The whole-liver coverage T1rho sequence at 3.0T was feasible for the assessment of segmental liver function. T1rho relaxation might be a potential biomarker for the estimation of liver function in LC patients.

Chemical salivary composition and its relationship with periodontal disease and dental calculus

Aim: To determine the relationship between the chemical composition of saliva, periodontal disease and dental calculus. Methods: An observational analytical cross-sectional study was conducted with patients over 55 years of age. Ethical principles of autonomy and risk protection were applied according to the international standards. Sociodemographic and diagnosis variables (presence of dental calculus and periodontal status) were considered to measure salivary concentrations of glucose (by the glucose oxidase/peroxidase method, amylase (by the colorimetric test), urea (by the amount of indophenol), total protein (by the Bradford method) and albumin (by the nephelometric method). Patients chewed a sterile rubber band and 3 mL of stimulated saliva were collected. The samples were stored at -5 °C, centrifuged at 2,800 rpm for 10 min, and the supernatant was removed and stored at -20 °C. Data were presented as frequencies and proportions for qualitative variables and measures of central tendency and dispersion for quantitative variables. Data were analyzed by either analysis of variance or Kruskal Wallis test . A p value <0.05 was considered statistically significant. Results: Significant relationships were observed between the concentration of salivary urea and periodontal status (p = 0.03) and the presence of dental calculus and urea (p = 0.04) was demonstrated. Conclusions: A relationship between the salivary urea concentration and the presence of periodontal disease and dental calculus is suggested.

Assessment of chemical exchange in tryptophan-albumin solution through (19)F multicomponent transverse relaxation dispersion analysis.

A number of NMR methods possess the capability of probing chemical exchange dynamics in solution. However, certain drawbacks limit the applications of these NMR approaches, particularly, to a complex system. Here, we propose a procedure that integrates the regularized nonnegative least squares (NNLS) analysis of multiexponential T2 relaxation into Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments to probe chemical exchange in a multicompartmental system. The proposed procedure was validated through analysis of (19)F T2 relaxation data of 6-fluoro-DL-tryptophan in a two-compartment solution with and without bovine serum albumin. Given the regularized NNLS analysis of a T2 relaxation curve acquired, for example, at the CPMG frequency υ CPMG  = 125, the nature of two distinct peaks in the associated T2 distribution spectrum indicated 6-fluoro-DL-tryptophan either retaining the free state, with geometric mean */multiplicative standard deviation (MSD) = 1851.2 ms */1.51, or undergoing free/albumin-bound interconversion, with geometric mean */MSD = 236.8 ms */1.54, in the two-compartment system. Quantities of the individual tryptophan species were accurately reflected by the associated T2 peak areas, with an interconversion state-to-free state ratio of 0.45 ± 0.11. Furthermore, the CPMG relaxation dispersion analysis estimated the exchange rate between the free and albumin-bound states in this fluorinated tryptophan analog and the corresponding dissociation constant of the fluorinated tryptophan-albumin complex in the chemical-exchanging, two-compartment system.

Assessment of higher order structure comparability in therapeutic proteins using nuclear magnetic resonance spectroscopy.

In this work, we applied nuclear magnetic resonance (NMR) spectroscopy to rapidly assess higher order structure (HOS) comparability in protein samples. Using a variation of the NMR fingerprinting approach described by Panjwani et al. [2010. J Pharm Sci 99(8):3334-3342], three nonglycosylated proteins spanning a molecular weight range of 6.5-67 kDa were analyzed. A simple statistical method termed easy comparability of HOS by NMR (ECHOS-NMR) was developed. In this method, HOS similarity between two samples is measured via the correlation coefficient derived from linear regression analysis of binned NMR spectra. Applications of this method include HOS comparability assessment during new product development, manufacturing process changes, supplier changes, next-generation products, and the development of biosimilars to name just a few. We foresee ECHOS-NMR becoming a routine technique applied to comparability exercises used to complement data from other analytical techniques.

Chemico-physical characterisation and in vivo biocompatibility assessment of DLC-coated coronary stents.

The vast majority of stent thrombosis occurs in the acute and sub-acute phases and is more common in patients with acute coronary syndromes, due to the thrombotic milieu where stent struts are positioned. Stent thrombosis is likely due to incomplete tissue coverage of metallic stents as the contact between metallic stents and blood elements may lead to platelet adhesion and trigger vessel thrombosis. If a stent is covered after 7 days, the risk that it will be found uncovered at later stages is very low (<1%). In this article, we demonstrate that diamond-like carbon (DLC) coatings, deposited by physical vapour deposition, promote rapid endothelisation of coronary stent devices, with very low platelets activation, reducing thrombotic clots. We relate these behaviours to the surface and bulk material properties of the DLC films, subjected to a comprehensive chemico-physical characterisation using several techniques (X-ray photoelectron spectroscopy, atomic force microscopy, field-emission scanning electron microscope, transmission electron microscopy combined with electron energy loss spectroscopy, Raman and dispersive X-ray spectroscopy). In vivo studies, conducted on 24 pigs, have shown complete endothelisation after 7 days, with no fibrin mesh and with only rare monocytes scattered on the endothelial layer while 30 and 180 days tests have shown reduced inflammatory activation and a complete stabilisation of the vessel healing, with a minimal neointimal proliferation. The integral and permanent DLC film coating improves haemo- and bio-compatibility and leads to an excellent early vessel healing of the stent whilst the extremely thin strut thickness reduces the amount of late neointima and consequently the risk of late restenosis. These data should translate into a reduced acute and sub-acute stent thrombosis.

Assessment of two immunodepletion methods: off-target effects and variations in immunodepletion efficiency may confound plasma proteomics.

Immunodepletion of abundant plasma proteins increases the depth of proteome penetration by mass spectrometry. However, the nature and extent of immunodepletion and the effect of off-target depletion on the quantitative comparison of the residual proteins have not been critically addressed. We performed mass spectrometry label-free quantitation to determine which proteins were immunodepleted and by how much. Two immunodepletion resins were compared: Qproteome (Qiagen) which removes albumin+immunoglobulins and Seppro IgY14+SuperMix (Sigma-Aldrich) which removes 14 target proteins plus a number of unidentified proteins. Plasma collected by P100 proteomic plasma collection tubes (BD) from 20 human subjects was individually immunodepleted to minimize potential variability, prior to pooling. The abundant proteins were quantified better when using only albumin+immunoglobulins removal (Qproteome), while lower abundance proteins were evaluated better using exhaustive immunodepletion (Seppro IgY14+SuperMix). The latter resin removed at least 155 proteins, 38% of the plasma proteome in protein number and 94% of plasma protein in mass. The depth of immunodepletion likely accounts for the effectiveness of this resin in revealing low abundance proteins. However, the more profound immunodepletion achieved with the IgY14+SuperMix may lead to false-positive fold-changes between comparison groups if the reproducibility and efficiency of the depletion of a given protein are not considered.

The paradigm shifting role of chromatographic methods in pharmaceutical analysis.

An overview is presented of the impact of chromatographic method developments on the quality control of pharmaceuticals as of the 1950s up until the present times. This survey is mainly based on the changes in pharmacopeias starting with United States Pharmacopeia (USP) 16, issued in 1960, up to the presently effective USP 34 and European Pharmacopeia 7.2. At the beginning of this period the role of chromatographic methods was negligible and was restricted to classical column chromatography and paper chromatography. However, the invention of high-performance liquid chromatography (HPLC) initiated a rapid paradigm shift in the attitude toward, and the use of, chromatographic methods. As a result, HPLC began a "career" of rapid spreading and development, and by now has undoubtedly become the principal method in pharmaceutical analysis. Likewise, the role of thin-layer chromatography (TLC) and to a lesser extent gas chromatography is also remarkable. The role of these and electrophoretic methods in the identification, assay and purity check of drugs and drug products in the modern pharmacopeias is discussed. As a case study the stability investigation of Depersolone® injection carried out in the 1960s and 35 years later is presented and the information obtainable from the classical and modern approach is compared.

Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI.

We report in vivo and in vitro MRI properties of six gadolinium-dendrimer and gadolinium-albumin conjugates of derivatized acyclic diethylenetriamine-N,N',N',N″, N″-pentaacetic acid (1B4M) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (C-DOTA). The three albumin-based agents have comparable protein to chelate ratios (1:16-18) as well as molar relaxivity (8.8-10.4 mM(-1) s(-1)). The three dendrimer based agents have blood clearance half-lives ranging from 17 to 66 min while that of the three albumin-based agents are comparable to one another (40-47 min). The dynamic image obtained from use of the albumin conjugate based on the macrocycle (C-DOTA) showed a higher contrast compared to the remaining two albumin based agents. Our conclusion from all of the results is that the macrocyclic-based (DOTA) agents are more suitable than the acyclic-based (1B4M) agent for in vivo use based on their MRI properties combined with the kinetic inertness property associated with the more stable Gd(III) DOTA complex.

Quantitative assessment of macromolecular concentration during direct infusion into an agarose hydrogel phantom using contrast-enhanced MRI.

Convection-enhanced delivery (CED), that is, direct tissue infusion, has emerged as a promising local drug delivery method for treating diseases of the nervous system. Determination of the spatial distribution of therapeutic agents after infusion is important in evaluating the efficacy of treatment, optimizing infusion protocols and improving the understanding of drug pharmacokinetics. In this study, we provide a methodology to determine the concentration distribution of Gd-labeled tracers during infusion using contrast-enhanced magnetic resonance imaging (MRI). To the best of our knowledge, MR studies that quantify concentration profiles for CED have not been previously reported. The methodology utilizes intrinsic material properties (T(1) and R(1)) and reduces the effect of instrumental factors (e.g., inhomogeneity of MR detection field). As a methodology investigation, this study used an agarose hydrogel phantom as a tissue substitute for infusion. An 11.1-T magnet system was used to image infusion of Gd-DTPA-labeled albumin (Gd-albumin) into the hydrogel. By using data from preliminary scans, Gd-albumin distribution was determined from the signal intensity of the MR images. As a validation test, MR-derived concentration profiles were found comparable to both results measured directly using quantitative optical imaging and results from a computational transport model in porous media. In future studies, the developed methodology will be used to quantitatively monitor the distribution of Gd tracer following infusion directly into tissues.

Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs.

We have used phage display to isolate a range of human domain antibodies (dAbs) that bind to mouse, rat and/or human serum albumin (SA) and can be expressed at very high levels in bacterial, yeast or mammalian cell culture. In contrast to non-SA-binding dAbs, which have terminal half-lives of less than 45 min, the half-lives of these 12 kDa 'AlbudAbs' can match the half-life of SA itself. To demonstrate the use of AlbudAbs for extending the half-lives of therapeutic drugs, we created a fusion of the interleukin-1 receptor antagonist (IL-1ra) with an AlbudAb. Soluble IL-1ra is potent inhibitor of IL-1 signalling that is approved for the treatment of rheumatoid arthritis but has a relatively short in vivo half-life. Here we show that although the AlbudAb/IL-1ra fusion has a similar in vitro potency, its in vivo efficacy can be dramatically improved due to its extended serum half-life. AlbudAbs could potentially be used to generate a range of long half-life versions of many different drugs in order to improve their dosing regimen and/or clinical effect.

Feasibility of mitral flow assessment by echo-contrast ultrasound, part I: determination of the properties of echo-contrast agents.

Data on the ultrasonic properties of commercially available contrast agents are limited by being instrument-dependent, especially with regard to their backscattering properties. The present work describes methods of measurements that provide instrument-independent estimations of a contrast agent's attenuation coefficient and integrated backscatter index and provide them as functions of its concentration. The two studied commercially available contrast agents were Albunex and Levovist SHU 508-A, both representative of agents in common use for echocardiography. The attenuation coefficients and integrated backscatter indices of both agents were found to be a linear function of their concentrations. Proportionality coefficients +/- their standard deviations are provided. Actually, square root values of the averaged backscatter indices normalized with respect to the rms of the reference signal were determined. The coefficients of proportionality were found to be: C(A) = 3.11+/-0.1813 dB/mm; C(L) = 0.07+/-0.005 dB/mm for attenuation coefficients of the Albunex and Levovist contrast agents, respectively, and the corresponding values for backscattering were: D(A) = 0.07+/-0.0054; D(L) = 0.02+/-0.0012. Being apparatus-independent, the findings of the study are important prerequisites for the use of these echo-contrast agents as an indicator in research for a quantitative assessment of blood flow.

2,4-toluenediisocyanate and hexamethylene-diisocyanate adducts with blood proteins: assessment of reactivity of amino acid residues in vitro.

Diisocyanates, reactive compounds used in plastics industry and potent occupational allergens, readily bind to proteins both in vitro and in vivo, however, the pattern of adducts with individual amino acids has not been investigated systematically. In this study, potential of the proteinogenic amino acid residues for carbamoylation with 2,4-toluenediisocyanate (2,4-TDI) and hexamethylenediisocyanate (HDI) was evaluated. The diisocyanates were incubated in an in vitro system (buffer pH 7.4/dioxane 50:50) with: (a) a series of Nalpha-benzyloxycarbonyl amino acids (Z-amino acids) and N-acetylcysteine (Ac-Cys), model compounds for non-N-terminal amino acids of the protein chain; (b) dipeptides Val-Phe and Asp-Phe, model compounds for N-termini of globin and albumin, respectively. Reactivity of the compounds tested, evaluated from their depletion during incubation with the diisocyanates (measured by HPLC), was in the order: Ac-Cys = Asp-Phe > Val-Phe = Nalpha-Z-Lys >> Nalpha-Z-His for 2,4-TDI, and Ac-Cys > Asp-Phe > Val-Phe = Nalpha-Z-Lys > Nalpha-Z-His > N-Z-Tyr for HDI, however, the adducts with Ac-Cys were unstable. Reactions of other amino acid residues (e.g. Ser, Thr, Met, Trp, Arg, Asn, Gln) with 2,4-TDI and HDI were not observed. Thus, N-terminal amino acids and Lys residues are likely to produce most abundant adducts with diisocyanates in proteins. Further, three amino compounds with increasing pKa values (Val-Phe, Val and Nalpha-Z-Lys) were incubated with 2,4-TDI and N-acetyl-S-[4-(2-amino)tolylcarbamoyl]cysteine, a 2,4-TDI-derived thiocarbamate with carbamoylating activity, in media with 10% and no dioxane, respectively. Here, reactivity of the amino compounds was decreasing in the order: Val-Phe > Val > Nalpha-Z-Lys, which reflects the mechanism of the amine-isocyanate reaction. The experiments also demonstrate the effect of a solvent (organic phase content) on the yield of the carbamoylation reactions.

An albumin-coated polyester arterial graft: in vivo assessment of biocompatibility and healing characteristics.

The albumin-coated vascular graft (ACG) and its uncoated polyester substrate, the Vascular II (V-II), were evaluated in terms of biocompatibility and biofunctionality using two in vivo animal studies. Biocompatibility and immunoreactivity were assessed by implanting intraperitoneally in the rat small segments of the ACG and the V-II graft and harvesting them with their surrounding tissue 3d, 1, 2 and 4 weeks later. Cytofluorometric determination of total T cells (CD3), the ratio of CD4/CD8 subsets and the percentage of IL-2 receptor-positive T cells in the peripheral blood has revealed that no significant difference in any of the T cell populations was found between the ACG and the V-II graft. The cellular reactivity of the ACG in terms of acid phosphatase activity at the implant side was significantly greater at 3 d but not at longer periods. Biofunctionality was evaluated by implanting both grafts as a thoracoabdominal vascular bypass in dogs for 11 different periods ranging from 4 h to 6 months. The rate of albumin resorption was such that traces were still present at 1 month, but no longer observable at 2 months. Tissue incorporation into the graft wall was earlier for the V-II (2 weeks) than for the ACG (4 weeks), which showed complete encapsulation, tissue incorporation and endothelialization after 2 months in vivo. Only small differences were observed between both grafts in terms of platelet and fibrin uptake on the luminal surface. The prostacyclin/thromboxane A2 ratio increased to a level higher that 1.0 aorta within 1 month for the V-II and 4 months for the ACG. In conclusion, the Bard ACG has demonstrated excellent biocompatibility in terms of blood T cell behaviour and acid phosphatase activity at the implant site. Finally, its healing response is equivalent to that of the uncoated Dacron prosthesis once the albumin coating has been resorbed.

A simple method for the assessment of macrophage scavenger receptor-ligand interaction: adherence of erythrocytes coated with oxidized low density lipoprotein and modified albumin to macrophages.

A simple method is described for the assessment of the binding of macrophage scavenger receptor and its ligands such as oxidized low density lipoprotein (ox-LDL) and maleylated bovine serum albumin (m-BSA). In this method, the binding of ox-LDL or m-BSA to macrophages is observed as the adherence of erythrocytes precoated with ox-LDL or m-BSA under phase-contrast microscopy. Erythrocytes were coated with native LDL or ox-LDL simply by incubating mouse erythrocytes with LDL. The ox-LDL-coated erythrocytes attached to the monolayer of mouse peritoneal macrophages without phagocytosis at 37 degrees C, while native LDL-coated erythrocytes did not. The extent of the adherence of the ox-LDL-coated erythrocytes to the macrophages was conveniently expressed as the proportion of the macrophages binding the coated erythrocytes. An optimal concentration of ox-LDL for erythrocyte coating giving maximum erythrocyte adherence to macrophages was 10 micrograms/ml as protein at an erythrocyte concentration of 2%. The binding of the ox-LDL-coated erythrocytes to the macrophages could be inhibited by ligands for scavenger receptor, and reflected the extent of LDL oxidation. Mouse erythrocytes were successfully coated with m-BSA using chromium(III) ion as adsorbent. The m-BSA-coated erythrocytes attached to the macrophages, while native BSA-coated erythrocytes did not. The adherence was inhibitable with ligands for scavenger receptor, and reflected the extent of maleylation. The method would be useful particularly for measurement of the ligand-binding activity of the receptor, and the receptor-binding activity of the ligands.

Oncotic pressure, albumin and ileus: the effect of albumin replacement on postoperative ileus.

The effect of decreased colloid oncotic pressure, as seen in hypoalbuminemia and hypoproteinemia, upon intestinal function has been well delineated in the surgical literature. Patients undergoing abdominal aortic aneurysm resection or aortoiliac or aortofemoral bypass grafts are almost uniformly hypoalbuminemic postoperatively; with these two facts in mind, a prospective, randomized clinical study was undertaken to identify the role of serum albumin concentration on the length of postoperative ileus in this population. The main hypothesis was that patients whose albumin levels dropped below 3.5 gm/dL would have a more prolonged postoperative hospital course as a result of delay in return of bowel function when compared with those patients in whom the low albumin levels were exogenously acutely replenished to > 3.5 gm/dL. Albumin was replaced to a level greater-than or equal to 3.5 g/dL in one group of 37 patients (AR), with a control group of 32 patients (NR) not receiving any albumin. Return of bowel function was measured by the postoperative day that flatus was documented, as well as the postoperative day oral intake was resumed. Mean values were determined for each group, and t tests did not reveal a significant difference in postoperative day of flatus (AR mean = 4.06 days, NR mean = 4.16 days) or postoperative day of oral intake (AR mean = 4.0, NR mean = 3.75). Additional comparisons between the groups involving the number of postoperative days until a regular diet was begun (AR mean = 6.06, NR mean = 5.48) and length of postoperative hospital stay (AR mean = 9.16, NR mean = 8.43) failed to reveal significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)