Evaluation for Blood Concentration and Efficacy/Safety of Continuous Administration of Thiamylal in Children.

BACKGROUND: Thiamylal exerts excellent sedative effects. However, it is not routinely used because of its serious adverse effects. This study aimed to clarify the target blood concentration range and infusion rate of thiamylal in children by measuring its blood concentration and evaluating its relationship with efficacy and adverse effects. METHODS: This study was approved by the Ethics Committee of Japanese Red Cross Kumamoto Hospital. The authors included 10 children aged between 1 and 7 years who had received continuous intravenous (IV) infusion of thiamylal for the management of refractory status epilepticus, excluding those who met the exclusion criteria. After a 2 mg/kg bolus injection of thiamylal, continuous IV infusion was initiated at a rate of 2-3 mg/kg/h. Thiamylal concentration in the blood was measured using high-performance liquid chromatography. The State Behavioral Scale and the frequency of bolus injections were used to evaluate efficacy. Blood pressure and heart rate were measured to evaluate adverse effects. Statistical analyses of the time to awakening and the factors affecting it were also conducted. RESULTS: The State Behavioral Scale score during thiamylal administration was -2 or lower in all cases, suggesting that the depth of sedation was sufficient. The frequency of bolus injections decreased in a blood concentration-dependent manner, suggesting that the frequency tended to decrease, especially at thiamylal blood concentrations of 20 mcg/mL or higher. An increase of the infusion rate to 3 mg/kg/h was recommended, because the blood concentration may not reach 20 mcg/mL at an infusion rate of 2 mg/kg/h. There was also a case in which a rapid increase in blood concentration accompanied by a decrease in blood pressure and heart rate was observed when the infusion rate was increased to 4 mg/kg/h. Furthermore, the time to awakening after the end of administration correlated with the highest blood concentration during administration; therefore, delayed awakening was noted when using a high dose of thiamylal. CONCLUSIONS: The target blood concentration of thiamylal in children should be 20-30 mcg/mL, and the infusion rate should be based on 3 mg/kg/h.

Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

OBJECTIVES: Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. MATERIALS AND METHODS: This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. RESULTS: Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. CONCLUSION: Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Factors influencing glomerular filtration rate as estimated using preoperative creatinine and cystatin C levels.

OBJECTIVES: Estimated glomerular filtration rate (eGFR) using serum creatinine (Cr) is commonly used to evaluate renal function. However, it can be influenced by other factors, which can risk the overestimation of the true GFR. Impaired renal function prior to cardiovascular surgery reportedly increases mortality and the incidence of postoperative complications. Thus, overestimation of renal function may affect the assessment of postoperative complication risks. Therefore, we aimed to compare the eGFR calculated from serum Cr and cystatin C (Cys-C) levels to assess preoperative renal function and to investigate factors affecting renal function overestimation. MATERIALS AND METHODS: 88 patients admitted for cardiovascular surgery who had preoperative serum Cr and Cys-C measurements were included in the study. Correlations between factors associated with eGFR calculated from serum Cr (eGFRcre) and Cys-C (eGFRcys) and their ratio (eGFRcre/eGFRcys) were examined using multiple regression analysis. RESULTS: Multiple regression analysis revealed that eGFRcre/eGFRcys was significantly negatively correlated with the Short Physical Performance Battery score (SPPB). A clinically significant difference in renal function overestimation was defined as GFRcre/eGFRcys > 1.2, with a cutoff value of 9 points for the SPPB score. The chair stand test, a component of the SPPB, had the same discriminative power as the SPPB for identification of renal function overestimation. CONCLUSION: The SPPB can be used to identify likely GFR overestimation in patients. Additionally, the chair stand test may be used as an alternative to the SPPB for the identification of renal function overestimation when the SPPB is difficult to perform.

High-Sensitivity and High-Throughput Quantification of Everolimus in Human Whole Blood Using Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry.

BACKGROUND: Rigorous dose adjustment by therapeutic drug monitoring (TDM) is recommended when everolimus (EVR) is administered for immunosuppression. In this study, the authors developed a highly sensitive ultrahigh-performance liquid chromatography coupled with the tandem mass spectrometry (UHPLC-MS/MS) method for measuring EVR concentrations in whole blood using a high-throughput solid-phase extraction method for sample pretreatment. Furthermore, the blood EVR concentrations in routine TDM samples from patients who underwent renal transplantation measured using the established UHPLC-MS/MS method were compared with those measured using the latex agglutination turbidimetric immunoassay (LTIA). METHODS: Blood samples were pretreated by solid-phase extraction using a 96-well HLB µElution plate. The clinical application of the newly developed method was evaluated using 87 blood samples from 19 patients who underwent kidney transplant. RESULTS: The calibration curve showed good linearity over a wide range of 0.1-50 ng/mL, with relative error ≤15% obtained from the back calculation of calibrators, and ≤20% for the lower limit of quantification. Within-batch and batch-to-batch accuracies and precisions fulfilled the acceptance criteria of the US Food and Drug Administration guidelines for bioanalytical method validation. The extraction recovery rates were good (≥65.2%), and almost no matrix effects were found in any of the quality control samples. Blood EVR concentrations measured by UHPLC-MS/MS were positively correlated with those measured by LTIA. A Bland-Altman plot indicated that the UHPLC-MS/MS method yielded better measurements than the LTIA method, regardless of the concentration. CONCLUSIONS: Therefore, the authors succeeded in developing a novel high-sensitivity and high-throughput method for measuring blood EVR concentration by UHPLC-MS/MS using a µElution plate for sample pretreatment.

Comparison between the Effects of Loxoprofen and Acetaminophen on Postoperative Pain Following Radical Prostatectomy: A Propensity Score Matching Analysis.

Non-steroidal anti-inflammatory medications are associated with renal impairment. However, there is little information on whether these medications affect postoperative renal function compared with acetaminophen. The objective of this study was to compare the effects of acetaminophen and loxoprofen, used as postoperative analgesic, effect on postoperative analgesia using propensity score matching analysis. We retrospectively enrolled 328 patients treated with loxoprofen or acetaminophen after open radical prostatectomy between October 2017 and February 2020. We analyzed postoperative pain intensity, the incidence rate of acute kidney injury, drug-induced liver injury, and rate of elevation in serum creatinine after open radical prostatectomy. Eighty-one matched pairs of patients treated with loxoprofen or acetaminophen were selected using propensity score matching analysis. The postoperative numerical rating scale was significantly higher in the acetaminophen group than in the loxoprofen group on postoperative day 5. The use of patient-controlled anesthesia and rescue analgesics was significantly higher in the acetaminophen group than in the loxoprofen group. The loxoprofen group had a significantly higher postoperative increase in serum creatinine than the acetaminophen group on postoperative days 5 and 8. The incidence of acute kidney injury was 4.9% in the loxoprofen group and 0% in the acetaminophen group, while the incidence of drug-induced liver injury was 0% in both groups. Acetaminophen appears to be safer than loxoprofen in terms of effects on renal function. Nevertheless, the number of acetaminophen doses and the dose per dose may need to be increased for patients with significant postoperative pain.

Evaluation of renal function using cystatin C-based estimated glomerular filtration rate in patients with urothelial carcinoma treated with gemcitabine and cisplatin chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Cisplatin-based chemotherapy is a first-line treatment for advanced or metastatic urinary tract urothelial carcinoma (UC). Accurate assessment of renal function is indispensable for determining cisplatin dosing to enhance the safety and effectiveness of cisplatin. The objective of this study was to assess serum cystatin C (sCys C) levels in patients with urothelial carcinoma and to explore its clinical value as a serum marker of glomerular filtration rate (GFR). METHODS: This study retrospectively enrolled 18 UC patients treated with a combination of gemcitabine and cisplatin between April 2018 and November 2020. We calculated the estimated GFR (eGFR) based on serum creatinine (sCr) or sCys C and estimated Cr clearance (eCCr) based on sCr. The correlation, bias, accuracy and creatinine height index between eGFR or eCCr and measured GFR (mGFR) based on Cr clearance were calculated from urinary Cr and sCr. RESULTS AND DISCUSSION: Estimated GFR based on sCys C correlated most strongly with mGFR. Moreover, the bias, mean error, mean absolute error and root mean square error were significantly lower in eGFRs based on sCyc C than in eGFRs based on sCr and eCCr. The correlation between eGFR based on sCys C/mGFR and creatinine height index was weaker than that between eGFR based on sCr/mGFR and creatinine height index, suggesting that sCys C was less affected by muscle mass. WHAT IS NEW AND CONCLUSION: In UC patients, eGFR based on sCys C reflected renal function more accurately than eGFR based on sCr, suggesting that sCys C may be useful for assessing renal function in clinical practice.

Effect of Cinacalcet on the Redox Status of Albumin in Secondary Hyperparathyroidism Patients Receiving Hemodialysis.

Chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT) have an increased risk of cardiovascular disease (CVD). Cinacalcet is a calcimimetic that permits impaired endothelial functions to be recovered via inhibiting parathyroid hormone (PTH) production in SHPT patients. However, the underlying mechanism for its action remains unknown. The purpose of this study was to examine the effect of cinacalcet on the redox state of human serum albumin (HSA), a reliable marker for assessing endothelial oxidative damage in SHPT patients who were receiving hemodialysis. Cinacalcet was administered to six SHPT patients for a period of 8 weeks. After 4 weeks of treatment, cinacalcet significantly decreased the oxidized albumin ratio which is a ratio of reduced and oxidized forms of HSA via increasing reduced form of HSA. Moreover, the radical scavenging abilities of HSA that was isolated from SHPT patients were increased by cinacalcet, suggesting the recovery of the impaired vascular anti-oxidant ability. Interestingly, the oxidized albumin ratio in SHPT patients was significantly higher than that in hemodialysis patients. In addition, the changes of intact PTH levels were significantly correlated with the oxidized albumin ratio. It therefore appears that PTH may induce oxidative stress in SHPT patients. In fact, an active analogue of PTH increased the production of reactive oxygen species in human endothelial cells. Thus, cinacalcet exhibits anti-oxidative activity through its pharmacological action. Additionally, cinacalcet itself showed radical scavenging activity. In conclusion, cinacalcet improves the redox status of HSA by inhibiting PTH production and partially by its radical scavenging action.

Down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism.

Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes. These effects were prevented by administration of the calcimimetic cinacalcet, a PTH suppressor, suggesting that PTH may down-regulate ABCG2 expression. This was directly tested in intestinal Caco-2 cells where the expression of ABCG2 on the plasma membrane was down-regulated by PTH (1-34) while its mRNA level remained unchanged. Interestingly, an inactive PTH derivative (13-34) had no effect, suggesting that a posttranscriptional regulatory system acts through the PTH receptor to regulate ABCG2 plasma membrane expression. As found in an animal study, additional clinical investigations showed that treatment with cinacalcet resulted in significant reductions in serum urate levels together with decreases in PTH levels in patients with secondary hyperparathyroidism undergoing dialysis. Thus, PTH down-regulates ABCG2 expression on the plasma membrane to suppress intestinal and renal urate excretion, and the effects of PTH can be prevented by cinacalcet treatment.

The Binding of Silibinin, the Main Constituent of Silymarin, to Site I on Human Serum Albumin.

Silibinin is the main constituent of silymarin, an extract from the seeds of milk thistle (Silybum marianum). Because silibinin has many pharmacological activities, extending its clinical use in the treatment of a wider variety of diseases would be desirable. In this study, we report on the binding of silibinin to plasma proteins, an issue that has not previously been extensively studied. The findings indicated that silibinin mainly binds to human serum albumin (HSA). Mutual displacement experiments using ligands that primarily bind to sites I and II clearly revealed that silibinin binds tightly and selectively to site I (subsites Ia and/or Ic) of HSA, which is located in subdomain IIA. Thermodynamic analyses suggested that hydrogen bonding and van der Waals interactions are major contributors to silibinin-HSA interactions. Furthermore, the binding of silibinin to HSA was found to be decreased with increasing ionic strength and detergent concentration of the media, suggesting that electrostatic and hydrophobic interactions are involved in the binding. Trp214 and Arg218 were identified as being involved in the binding of silibinin to site I, based on binding experiments using chemically modified- and mutant-HSAs. In conclusion, the available evidence indicates that silibinin binds to the region close to Trp214 and Arg218 in site I of HSA with assistance by multiple forces and can displace site I drugs (e.g., warfarin or iodipamide), but not site II drugs (e.g., ibuprofen).

Effect of a Ferric Citrate Formulation, a Phosphate Binder, on Oxidative Stress in Chronic Kidney Diseases-Mineral and Bone Disorder Patients Receiving Hemodialysis: A Pilot Study.

A ferric citrate formulation for treating hyperphosphatemia is a new therapeutic that not only suppresses the accumulation of phosphorus in patients with chronic kidney disease-mineral bone disorders (CKD-MBD), but also ameliorates anemia caused by iron deficiency. In contrast, it has been demonstrated that intravenous iron injection markedly increases oxidative stress. This study was designed to investigate the effect of a ferric citrate formulation on oxidative stress in CKD-MBD patients receiving hemodialysis therapy. Fifteen CKD-MBD patients undergoing dialysis were enrolled in this study. The patients were orally administered a ferric citrate formulation for 6 months. Their plasma phosphorus concentrations remained unchanged with the switch from other phosphorus adsorbents to the ferric citrate formulation. In addition, the ferric citrate formulation generally allowed for dose reduction of an erythropoiesis stimulating agent with an increased hematopoietic effect. The average values of plasma ferritin level increased after the introduction of a ferric citrate formulation, but did not exceed 100 (ng/mL). Interestingly, oxidative stress markers did not increase significantly, and anti-oxidative capacity was not significantly decreased at 6 months after the drug administration. Similarly, no change was observed in any inflammation markers. The ferric citrate formulation induces negligible oxidative stress in CKD-MBD patients receiving dialysis under the present clinical condition.

[Clinical study of long-term docetaxel based chemotherapy treatment for patients with castration-resistant prostate cancer].

PURPOSE: To evaluate long-term continuous administration of docetaxel (DOC), over survival rate, PSA level and adverse effects were analyzed, retrospectively. We also compared the results of long-term treatment group and short-term treatment group. MATERIAL AND METHODS: This study reported that 14 cases of long-term continuous administration of DOC consisting of 11 or more cycles among 51 patients of castration-resistant prostate cancer (CRPC) treated with DOC from October 2008 to September 2013 at our institution, retrospectively. Nineteen patients who had treated with DOC 10 or less cycles were defined as short-term dose group, and both groups were compared. DOC was administered every 3 to 4 weeks at 60 to 70 mg/m2, and was treated with prednisolone at 10 mg/day as a general. RESULTS: The median number of treatment cycles was 15. Thirteen cases showed a decrease in PSA levels and 10 cases showed a decrease in PSA levels of 50% or more, the 1-year survival rate of long-term dose and short-term dose group were 100% and 16%. Adverse effects of grade 3 or lower consisted of leukocytopenia in 85% and thrombocytopenia in 28%, however, grade 4 or higher were not observed in long-term dose group. In multivariable analysis of parameters, long-term treatment was related to PSA levels at start of treatment and ALP levels. CONCLUSION: Forty-two percent of patients who have CRPC at our institution undergo long-term DOC based chemotherapy treatment It may be suggested that long-term DOC based chemotherapy for some cases contribute to extend survival time with no serious adverse events.

Interaction between two sulfate-conjugated uremic toxins, p-cresyl sulfate and indoxyl sulfate, during binding with human serum albumin.

Recently, p-cresyl sulfate (PCS) has been identified as a protein-bound uremic toxin. Moreover, the serum-free concentration of PCS, which is associated with its efficacy of hemodialysis, appears to be a good predictor of survival in chronic kidney disease (CKD). We previously found that PCS interacts with indoxyl sulfate (IS), another sulfate-conjugated uremic toxin, during renal excretion via a common transporter. The purpose of this study was to further investigate the interaction between PCS and IS on the binding to human serum albumin (HSA). Here, we used ultrafiltration to show that there is only one high-affinity binding site for PCS, with a binding constant on the order of 10(5) M(-1) (i.e., comparable to that of IS). However, a binding constant of the low-affinity binding site for PCS is 2.5-fold greater than that for IS. Displacement of a fluorescence probe showed that PCS mainly binds to site II, which is the high-affinity site for PCS, on HSA. This finding was further supported by experiments using mutant HSA (R410A/Y411A) that displayed reduced site II ligand binding. A Klotz analysis showed that there could be competitive inhibition between PCS and IS on HSA binding. A similar interaction between PCS and IS on HSA was also observed under the conditions mimicking CKD stage 4 to 5. The present study suggests that competitive interactions between PCS and IS in both HSA binding and the renal excretion process could contribute to fluctuations in their free serum concentrations in patients with CKD.

Benzbromarone Attenuates Oxidative Stress in Angiotensin II- and Salt-Induced Hypertensive Model Rats.

Oxidative stress induced by hyperuricemia is closely associated with the renin-angiotensin system, as well as the onset and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). It is therefore important to reduce oxidative stress to treat hyperuricemia. We previously found that benzbromarone, a uricosuric agent, has a direct free radical scavenging effect in vitro. The antioxidant effects of benzbromarone were evaluated in vivo via oral administration of benzbromarone for 4 weeks to model rats with angiotensin II- and salt-induced hypertension. Benzbromarone did not alter plasma uric acid levels or blood pressure but significantly reduced the levels of advanced oxidation protein products, which are oxidative stress markers. Furthermore, dihydroethidium staining of the kidney revealed a reduction in oxidative stress after benzbromarone administration. These results suggest that benzbromarone has a direct antioxidant effect in vivo and great potential to prevent CVD and CKD.

Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin.

Sodium 4-phenylbutyrate (PB) is clinically used as a drug for treating urea cycle disorders. Recent research has shown that PB also has other pharmacologic activities, suggesting that it has the potential for use as a drug for treating other disorders. In the process of drug development, preclinical testing using experimental animals is necessary to verify the efficacy and safety of PB. Although the binding of PB to human albumin has been studied, our knowledge of its binding to albumin from the other animal species is extremely limited. To address this issue, we characterized the binding of PB to albumin from several species (human, bovine, rabbit, and rat). The results indicated that PB interacts with 1 high-affinity site of albumin from these species, which corresponds to site II of human albumin. The affinities of PB to human and bovine albumins were higher than those to rabbit and rat albumin, and that to rabbit albumin was the lowest. Binding and molecular docking studies using structurally related compounds of PB suggested that species differences in the affinity are attributed to differences in the structural feature of the PB-binding sites on albumins (e.g., charge distribution, hydrophobicity, shape, or size).

An oral absorbent, surface-deacetylated chitin nano-fiber ameliorates renal injury and oxidative stress in 5/6 nephrectomized rats.

In this study, we report that surface-deacetylated chitin nano-fibers (SDACNFs) are more effective in decreasing renal injury and oxidative stress than deacetylated chitin powder (DAC) in 5/6 nephrectomized rats. An oral administration of low doses of SDACNFs (40mg/kg/day) over a 4 week period resulted in a significant decrease in serum indoxyl sulfate, creatinine and urea nitrogen levels, compared with a similar treatment with DAC or AST-120. The SDACNFs treatment also resulted in an increase in antioxidant potential, compared with that for DAC or AST-120. Immunohistochemical analyses also demonstrated that SDACNFs treated CRF rats showed a decrease in the amount of accumulated 8-OHdG compared with the CRF group. These results suggest that the ingestion of SDCH-NF results in a significant reduction in the levels of pro-oxidants, such as uremic toxins, in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation.

Potential therapeutic interventions for chronic kidney disease-associated sarcopenia via indoxyl sulfate-induced mitochondrial dysfunction.

BACKGROUND: Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice. METHODS: The in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6-nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non-treatment group and AST-120, L-carnitine, or teneligliptin treatment groups. RESULTS: In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC-1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co-incubation with an anti-oxidant, ascorbic acid, L-carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin-6 and atrophy-related factors such as myostatin and atrogin-1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG-1α and increased muscular autophagy, as reflected by decreased mitochondria-rich type I fibres. An AST-120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L-carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level. CONCLUSIONS: Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS-targeted and mitochondria-targeted interventions for treating CKD-induced muscle atrophy and decreased exercise endurance.

Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations.

On account of its long circulating half-life, human serum albumin (HSA) is susceptible to posttranslational modifications that can alter its functions. Here, we comprehensively compared the degree of posttranslational modifications with the functional impairment of HSA derived from 5 different commercially available albumin preparations and clarified their relationships. We used electrospray ionization-time of flight mass spectrometry to evaluate the degree of posttranslational modification of the entire HSA molecule that was associated with disease development and found that the fraction of Cys34-cysteinylated HSA (Cys-Cys34-HSA), a major form of oxidative modification, varied substantially among the albumin preparations. Meanwhile, no remarkable difference was found in the degree of glycated or N-terminal truncated HSA among the preparations tested. The nonosmotic pressure maintenance functions of HSA, such as its antioxidative and ligand-binding activities significantly differed among the preparations. Interestingly, the alternations of these functions showed a significantly negative correlation only with the Cys-Cys34-HSA fraction. These findings suggest that the Cys-Cys34-HSA fraction, as estimated by electrospray ionization-time of flight mass spectrometry can be used as a predictive marker for the functional impairment of albumin preparations and that it would be preferable to use albumin preparations with higher contents of functionally effective albumin that correspond to a lower degree of cysteinylation of Cys34 in clinical practice.