Changes In Albumin Concentration Research Articles

Mixtures of the Biologically Active Substances as Model Systems for Animal Blood Diagnostics

There are numerous biochemical and physical methods for agrobio- and nanomedical sciences. The real-time interfacial tension (RTIT) of various liquids is a powerful analytical method. The main aims of the present work are the following: to study the parameters of the RTIT of the mixtures based on some proteins, lipids, salts as the model systems for animal blood diagnostics. The greatest differences in the RTIT values observed at different concentrations for the aqueous dispersions: albumin: lipid: salt “at the short time of existence of the surface”. The high salt concentrations have some particular effects on RTIT values for these mixtures at all times. The changes in albumin concentration influence all RTIT values, but the changes in lipid concentration have insignificant influence and only “at the long time of existence of the surface”. Such data have high importance both for fundamental studies and for possible applications in animal and human medicine.

The effect of storage at 4°C on canine-specific albumin on product sterility and albumin concentration.

To determine if lyophilized canine-specific albumin (CSA) can be stored beyond the manufacturer recommended 6hours post-reconstitution without significant concern for bacterial growth. Laboratory research. Large private teaching hospital. Six bottles of lyophilized CSA were retrieved from a medical grade (4°C) refrigerator and were reconstituted with 0.9% NaCl to a 5% solution. Time to complete dissolution of all bottles at room temperature without agitation was recorded in minutes. A 1.5-mL sample was collected from each bottle at the following time points: time 0 (at the time of complete dissolution), and then 6, 12, and 24hours after removal from 4°C. Each aliquot was inoculated into a blood culture tube and was immediately submitted for aerobic and anaerobic bacterial culture. A positive and negative control were cultured at the 24-hour time point. At each time point, an additional 0.5-mL aliquot from each albumin bottle was collected, and these were combined to determine the average albumin concentration (g/L, g/dL) as measured by an in-house analyzer. The albumin was stored at 4°C between sample collection. The reconstitution of CSA and storage at 4°C for up to 24hours did not result in anaerobic or aerobic bacterial growth in any of the 24 cultured samples. Storage did not have a clinically significant effect on the albumin concentration of the solution. The average albumin concentration of all samples was 42g/L (4.2g/dL). No growth was noted in the negative control, and the positive control grew 4 strains of bacteria. It appears safe to use lyophilized CSA up to 24hours post-reconstitution without significant risk of bacterial growth or change in albumin concentration.

Prospective study comparing the outcome of a population-specific adjusted calcium equation to ionized calcium.

Calcium circulates bound to albumin and changes in albumin concentration will therefore affect total calcium measurements. In order to mitigate this, correction factors are frequently used. The most widely used correction equation was described by Payne and colleagues in 1973. This equation was derived from well-defined hospitalized patients' data. Current clinical practice is consistent with the general application of the adjusted calcium equation irrespective of clinical setting. This study aims to assess the validity of this approach by the derivation of a community care-specific adjusted calcium equation ('community equation') and the comparison of its performance to a hospitalized patient equation and ionized calcium. Retrospective data were collected according to Payne's criteria from an inpatient and community care setting. Data were used to derive the two equations: the in-patient equation and community equation. The outcome of these equations was compared with ionized calcium obtained from 123 healthy participants. The community equation correctly identified the calcium status of 92% of the 123 healthy participants, while the inpatient equation identified 46% only. Regression analysis against ionized calcium showed a higher R2 for the community equation than for the inpatient equation. Furthermore, we have shown that mean albumin and calcium concentrations are significantly different between these two populations. In this study, we found that the diagnostic accuracy of the adjusted calcium equation in ambulant patients was improved by the derivation of a population-specific equation for the community care setting.

Phospholipase-A2 receptor antibody, 24hours proteinuria, and serum albumin as indicators of cyclophosphamide efficacy in idiopathic membranous nephropathy.

BackgroundWe aimed to evaluate cyclophosphamide efficacy in the treatment of idiopathic membranous nephropathy (IMN) and explore the efficacy of phospholipase‐A2 receptor antibody (PLA2R‐Ab), 24 hours proteinuria, and serum albumin in predicting 6‐ and 12‐month treatment effects.MethodsA retrospective analysis was performed on 135 patients with IMN who followed up after treatment. The observation points were before, and after 3, 6, and 12 months of treatment. We collected clinical indicator data at each observation point and measured PLA2R‐Ab levels before and after 3‐month treatment.ResultsThe remission rates at 3, 6, and 12 months of cyclophosphamide therapy for patients with IMN were 41.4, 74.8, and 76.1%, respectively. Patients in whom PLA2R‐Ab turned negative within 3 months had high remission rates at 3, 6, and 12 months after treatment (P < .05). PLA2R‐Ab change at 3 months had a strong correlation with 24 hours proteinuria change at 6 months. The change in albumin concentration before and after 3‐month treatment was an independent variable related to remission rate at 6 months, and 24 hours proteinuria change before and after 6‐month treatment was an independent variable related to remission rate at 12 months after treatment.ConclusionCyclophosphamide showed good efficacy at 3, 6, and 12 months for patients with IMN. Serum albumin change and PLA2R‐Ab change at 3 months can be used as indicators to predict remission at 6 months, respectively. Moreover, 24 hours proteinuria change at 6 months can predict remission at 12 months.

Investigating the Role of Altered Systemic Albumin Concentration on the Disposition of Theophylline in Adult and Pediatric Patients with Asthma by Using the Physiologically Based Pharmacokinetic Approach.

Theophylline is commonly used for the treatment of asthma and has a low hepatic clearance. The changes in plasma albumin concentration occurring in asthma may affect the exposure of theophylline. The aim of the presented work was to predict theophylline pharmacokinetics (PK) after incorporating the changes in plasma albumin concentration occurring in patients with asthma into a physiologically based pharmacokinetic (PBPK) model to see whether these changes can affect the systemic theophylline concentrations in asthma. The PBPK model was developed following a systematic model building approach using Simcyp. The predictions were performed initially in healthy adults after intravenous and oral drug administration. Only when the developed adult PBPK model had adequately predicted theophylline PK in healthy adults, the changes in plasma albumin concentrations were incorporated into the model for predicting drug exposure in patients with asthma. After evaluation of the developed model in the adult population, it was scaled to children on physiologic basis. The model evaluation was performed by using visual predictive checks and comparison of ratio of observed and predicted (Robs/Pre) PK parameters along with their 2-fold error range. The developed PBPK model has effectively described theophylline PK in both healthy and diseased populations, as Robs/Pre for all the PK parameters were within the 2-fold error limit. The predictions in patients with asthma showed that there were no significant changes in PK parameters after incorporating the changes in serum albumin concentration. The mechanistic nature of the developed asthma-PBPK model can facilitate its extension to other drugs. SIGNIFICANCE STATEMENT: Exposure of a low hepatic clearance drug like theophylline may be susceptible to plasma albumin concentration changes that occur in asthma. These changes in systemic albumin concentrations can be incorporated into a physiologically based pharmacokinetic model to predict theophylline pharmacokinetics in adult and pediatric asthma populations. The presented work is focused on predicting theophylline absorption, distribution, metabolism, and elimination in adult and pediatric asthma populations after incorporating reported changes in serum albumin concentrations to see their impact on the systemic theophylline concentrations.

Effect of Protein Binding on Exposure of Unbound and Total Mycophenolic Acid: A Population Pharmacokinetic Analysis in Chinese Adult Kidney Transplant Recipients.

ObjectivesThe population pharmacokinetic (popPK) characteristics of total mycophenolic acid (tMPA) have been investigated in various ethnic populations. However, investigations of popPK of unbound MPA (uMPA) are few. Thus, a popPK analysis was performed to: (1) characterize the PK of uMPA and tMPA and its 7-O-mycophenolic acid glucuronide (MPAG) metabolite in kidney transplant patients cotreated with cyclosporine (CsA), and (2) identify the clinically significant covariates that explain variability in the dose–exposure relationship.MethodsA total of 740 uMPA, 741 tMPA, and 734 total MPAG (tMPAG) concentration–time data from 58 Chinese kidney transplant patients receiving MPA in combination with CsA were analyzed using NONMEM® software with the stochastic approximation expectation maximization (SAEM) followed by the important sampling (IMP) method. The influence of covariates was tested using a stepwise procedure.ResultsThe PK of uMPA and unbound MPAG (uMPAG) were characterized by a two- and one-compartment model with first-order elimination, respectively. A linear protein binding model was used to link uMPA and tMPA. Apparent clearance (CL/F) and central volume of distribution (VC/F) of uMPA (CLuMPA/F and VCuMPA/F, respectively) and protein binding rate constant (kB) were estimated to be 851 L/h [relative standard error (RSE), 7.1%], 718 L (18.5%) and 53.4/h (2.3%), respectively. For uMPAG, the population values (RSE) of CL/F (CLuMPAG) and VC/F (VCuMPAG/F) were 5.71 L/h (4.4%) and 29.9 L (7.7%), respectively. Between-subject variability (BSVs) on CLuMPA/F, VCuMPA/F, CLuMPAG/F, and VCuMPAG/F were 51.0, 80.0, 31.8 and 48.4%, respectively, whereas residual unexplained variability (RUVs) for uMPA, tMPA, and uMPAG were 47.0, 45.9, and 22.0%, respectively. Significant relationships were found between kB and serum albumin (ALB) and between CLuMPAG/F and glomerular filtration rate (GFR). Additionally, model-based simulation showed that changes in ALB concentrations substantially affected tMPA but not uMPA exposure.ConclusionsThe established model adequately described the popPK characteristics of the uMPA, tMPA, and MPAG. The estimated CLuMPA/F and unbound fraction of MPA (FUMPA) in Chinese kidney transplant recipients cotreated with CsA were comparable to those published previously in Caucasians. We recommend monitoring uMPA instead of tMPA to optimize mycophenolate mofetil (MMF) dosing for patients with lower ALB levels.

Development and Evaluation of Physiologically Based Pharmacokinetic Drug-Disease Models for Predicting Rifampicin Exposure in Tuberculosis and Cirrhosis Populations.

The physiologically based pharmacokinetic (PBPK) approach facilitates the construction of novel drug–disease models by allowing incorporation of relevant pathophysiological changes. The aim of the present work was to explore and identify the differences in rifampicin pharmacokinetics (PK) after the application of its single dose in healthy and diseased populations by using PBPK drug–disease models. The Simcyp® simulator was used as a platform for modeling and simulation. The model development process was initiated by predicting rifampicin PK in healthy population after intravenous (i.v) and oral administration. Subsequent to successful evaluation in healthy population, the pathophysiological changes in tuberculosis and cirrhosis population were incorporated into the developed model for predicting rifampicin PK in these populations. The model evaluation was performed by using visual predictive checks and the comparison of mean observed/predicted ratios (ratio(Obs/pred)) of the PK parameters. The predicted PK parameters in the healthy population were in adequate harmony with the reported clinical data. The incorporation of pathophysiological changes in albumin concentration in the tuberculosis population revealed improved prediction of clearance. The developed PBPK drug–disease models have efficiently described rifampicin PK in tuberculosis and cirrhosis populations after administering single drug dose, as the ratio(Obs/pred) for all the PK parameters were within a two-fold error range. The mechanistic nature of the developed PBPK models may facilitate their extension to other diseases and drugs.

PKB is a central molecule in the modulation of Na+-ATPase activity by albumin in renal proximal tubule cells

Evidence points to a possible role of tubular sodium reabsorption in worsening renal injury. Proximal tubule (PT) albumin overload is a critical process in the development of tubule-interstitial injury (TII), and consequently in progression of renal disease. We studied the possible correlation between changes in albumin concentration in the lumen of PT with modification of Na+-ATPase activity. An albumin overload animal model and LLC-PK1 cells as a model of PT cells were used. Albumin overload was induced by intraperitoneal injection of BSA in 14-week-old male Wistar rats. An increase in sodium clearance, fractional excretion of sodium, proteinuria, ratio between urinary protein and creatinine, and albuminuria were observed. These observations indicate that there could be a correlation between an increase in albumin in the lumen of PTs and renal sodium excretion. We observed that the activity of both Na+-ATPase and (Na++K+)ATPase decreased in the renal cortex of an albumin overload animal model. Using LLC-PK1 cells as a model of PT cells, inhibition of Na+-ATPase activity was observed with higher albumin concentrations, similar to that observed in the animal model. The inhibition of protein kinase B by higher albumin concentration was found to be a critical step in the inhibition of Na+-ATPase activity. Interestingly, activation of the ERK1/2/mTORC1/S6K pathway was required for protein kinase B inhibition. This mechanism leads to a decrease in protein kinase C activity and, consequently to inhibition of Na+-ATPase activity. Taken together, our results indicate that the molecular mechanism underlying the modulation of PT Na+-ATPase activity by albumin overload involves activation of the ERK1/2/mTORC1/S6K pathway, which leads to inhibition of the mTORC2/PKB/PKC pathway. Our findings contribute to better understanding regarding handing of renal Na+ induced by albumin overload in the lumen of PTs and, consequently, in the progression of renal disease.

Effects of dexmedetomidine on alveolar fluid clearance in rats with acute lung injury induced by lipopolysaccharide

Objective To investigate effects of dexmedetomidine(Dex) on alveolar fluid clearance (AFC) in rats with acute lung injury induced by lipopolysaccharide (LPS). Methods Forty-eight male Wistar rats were randomly divided into normal saline control (NS) group, LPS group, and Dex treatment (LPS+Dex) group. The rats in NS group were intravenously injected with 0.9% normal saline (5 ml/kg) followed by influsion of 0.9% normal saline (5 μg·kg-1·h-1). The rats in LPS group were intravenously injected with LPS (10 mg/kg) followed by influsion of 0.9% normal saline (5 μg·kg-1·h-1). The rats in LPS+Dex group were intravenously injected with LPS (10 mg/kg) followed by influsion of Dex (5 μg·kg-1·h-1). The rats were sacrificed 6 h after intravenous injection of LPS or NS, PaO2 was measured, AFC was determined by Evans blue-tagged albumin concentration changes. Histology of the lungs were assayed with H-E staining. The wet/dry weight ratio (W/D) of the lung was determined. The levels of TNF-α and IL-1β in the lung tissues were assessed by ELISA. The protein levels of potassium sodium adenosine triphosphate enzyme (Na-K-ATPase), alveolar epithelial sodium channel (ENaC) were detected by Western blot and immunohistochemistry. Results Compared with NS group, PaO2 was lower in LPS group, and this drop was reversed by Dex (in LPS+Dex group)(P<0.01). The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group, relative to the NS group, but the increases were compromised in the LPS+Dex group(P<0.01). AFC was reduced in LPS group, relative to NS group, but the reduction was compensat in LPS+Dex group(P<0.01). The expression of Na-K-ATPase and ENaC was lower in the LPS group than the NS group, but they were normalized in the LPS+Dex group(P<0.01). Conclusions Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing AFC and the expression of Na-K-ATPase and ENaC in rats with acute lung injury induced by lipopolysaccharide. Key words: Dexmedetomidine; Acute lung injury; Alveolar fluid clearance; Potassium sodium adenosine triphosphate enzyme; Alveolar epithelial sodium channel

Reduction in central venous pressure enhances erythropoietin synthesis: role of volume-regulating hormones.

Erythropoiesis is a tightly controlled biological event, but its regulation under non-hypoxic conditions, however, remains unresolved. We examined whether acute changes in central venous blood pressure (CVP) elicited by whole-body tilting affect erythropoietin (EPO) concentration according to volume-regulating hormones. Plasma EPO, angiotensin II (ANGII), aldosterone, pro-atrial natriuretic peptide (proANP) and copeptin concentrations were measured at supine rest and up to 3h during 30° head-up (HUT) and head-down tilt (HDT) in ten healthy male volunteers. Plasma albumin concentration was used to correct for changes in plasma volume and CVP was estimated through the internal jugular vein (IJV) aspect ratio with ultrasonography. From supine rest, the IJV aspect ratio was decreased and increased throughout HUT and HDT respectively. Plasma EPO concentration increased during HUT (13%; P=0.001, P for linear component=0.017), independent of changes in albumin concentration. Moreover, ANGII and copeptin concentrations increased during HUT, while proANP decreased. The increase in EPO concentration during HUT disappeared when adjusted for changes in copeptin. During HDT, EPO, ANGII and copeptin concentrations remained unaffected while proANP increased. In regression analyses, EPO was positively associated with copeptin (β=0.55; 95% CI=0.18, 0.93; P=0.004) irrespective of changes in other hormones and albumin concentration. Reduction in CVP prompts an increase in plasma EPO concentration independent of hemoconcentration and hence suggests CVP per se as an acute regulator of EPO synthesis. This effect may be explained by changes in volume-regulating hormones.

Serum albumin perturbations in cyanotics after cardiac surgery: Patterns and predictions.

Introduction:Hypoalbuminemia is a well-recognized predictor of general surgical risk and frequently occurs in patients with cyanotic congenital heart disease (CCHD). Moreover, cardiopulmonary bypass (CPB)-induced an inflammatory response, and the overall surgical stress can effect albumin concentration greatly. The objective of his study was to track CPB-induced changes in albumin concentration in patients with CCHD and to determine the effect of hypoalbuminemia on postoperative outcomes.Materials and Methods:Prospective observational study conducted in 150 patients, Group 1 ≤18 years (n = 75) and Group 2 >18 years (n = 75) of age. Albumin levels were measured preoperatively (T1), after termination of CPB (T2) and 48 h post-CPB (T3). Primary parameters (mortality, duration of postoperative ventilation, duration of inotropes and duration of Intensive Care Unit [ICU] stay) and secondary parameters (urine output, oliguria, arrhythmias, and hemodynamic parameters) were recorded.Results:The albumin levels in Group 1 at T1, T2, and T3 were 3.8 ± 0.48, 3.2 ± 0.45 and 2.6 ± 0.71 mg/dL; and in Group 2 were 3.7 ± 0.50, 3.2 ± 0.49 and 2.7 ± 0.62 mg/dL respectively. All patients showed a significant decrease in albumin concentration 48 h after surgery (P < 0.01). Analysis between the groups, however, showed no statistical difference. Eleven patients expired during the study period, and nonsurvivors showed significantly lower serum albumin concentration 48 h after surgery 2.3 ± 0.62 mg/dL versus 3.7 ± 0.56 mg/dL in the survivors (P < 0.05). Receiver operating characteristic curve showed that a baseline albumin cut-off value of 3.3 g/dL predicts mortality with a positive predictive value 47.6% and a negative predictive value of 99.2% (P < 0.05). A strong correlation was seen between albumin levels at 48 h with duration of CPB (r2 = 0.6321), ICU stay (r2 = 0.7447) and incidence of oliguria (r2 = 0.8803).Conclusions:The study demonstrated similar fall in albumin concentration in cyanotic patients (both adult and pediatric) in response to CPB. Low preoperative serum albumin concentrations (<3.3 g/dL) can be used to identify and prognosticate subset of cyanotics predisposed to additional surgical risk.

The effect of intravenous fresh frozen plasma administration on fibrinogen and albumin concentrations in sick neonatal foals

SummaryThis study investigated the immediate (6 h or less) effects of fibrinogen and albumin contained in transfused equine origin fresh frozen plasma on those proteins when measured in sick neonatal foals. Fibrinogen and albumin concentrations were measured in the administered plasma and in 31 sick foals at admission to a referral neonatal intensive care unit. Additional samples were obtained from the foals at 2 and 6 h following transfusion. No changes in albumin concentration were recognised. The main determinant of fibrinogen concentration following transfusion was the concentration of fibrinogen in the foal at admission. Importantly, intravenous transfusion of equine fresh frozen plasma did not result in immediate (6 h or less) increases or decreases in the fibrinogen concentration in the recipient foals. Fibrinogen from the donor contained within transfused plasma will not directly affect fibrinogen concentrations measured at later times.

Characterizing plasma albumin concentration changes in TB/HIV patients on anti retroviral and anti -tuberculosis therapy.

PurposePlasma albumin, a biomarker for hepatic function, is reported to correspondingly decrease in concentration as disease severity increases in chronic infections including HIV and TB. Our objective was to develop a semi-mechanistic disease progression model to quantify plasma albumin concentration changes during TB and HIV therapy and identify the associated covariate factors.MethodsPlasma albumin concentration data was collected at specified times for 3 months from 262 HIV participants receiving efavirenz based anti retroviral therapy. Of these, 158 were TB co-infected and on Rifampicin based anti –tuberculosis co-treatment. An indirect response model with zero order albumin production and first order elimination was developed in NONMEM version 7.2 to describe our data. Genotype (CYP2B6*6 and 11, CYP3A5, ABCB1c.3435C>T and ABCB1rs), TB disease status, baseline age, body weight, plasma creatinine, alanine transaminase enzyme and CD4+ count were the potential model covariates tested.ResultsThe proposed model successfully described plasma albumin concentration changes in the study population. There was a 10.9% and 48.6% increase in albumin production rates in HIV only and TB co-infected participants respectively. Participants co-infected with TB showed a 44.2% lower baseline albumin secretion rate than those without TB while ABCB1c.3435C>T mutation was associated with a 16% higher steady state albumin secretion rate following treatment.ConclusionA semi-mechanistic model describes plasma albumin concentration changes in HIV patients on ART. Further work is required to establish the utility of the model in monitoring disease progression and predicting prognosis in HIV and TB co-infected patients in absence of or during treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s40203-014-0003-9) contains supplementary material, which is available to authorized users.

Defining the role of albumin infusion in cirrhosis-associated hyponatremia.

The presence of negatively charged, impermeant proteins in the plasma space alters the distribution of diffusible ions in the plasma and interstitial fluid (ISF) compartments to preserve electroneutrality and is known as Gibbs-Donnan equilibrium. In patients with hypoalbuminemia due to underlying cirrhosis, the decrease in the plasma water albumin concentration ([Alb-]pw) would be expected to result in a decrease in the plasma water sodium concentration ([Na+]pw) due to an alteration in the distribution of Na+ between the plasma and ISF. In addition, cirrhosis-associated hyponatremia may be due to the renal diluting defect resulting from the intravascular volume depletion due to gastrointestinal losses and overdiuresis and/or decreased effective circulatory volume secondary to splanchnic vasodilatation. Therefore, albumin infusion may result in correction of the hyponatremia in cirrhotic patients either by modulating the Gibbs-Donnan effect due to hypoalbuminemia or by restoring intravascular volume in patients with intravascular volume depletion due to gastrointestinal losses and overdiuresis. However, the differential role of albumin infusion in modulating the [Na+]pw in these patients has not previously been analyzed quantitatively. In the present study, we developed an in vitro assay system to examine for the first time the quantitative effect of changes in albumin concentration on the distribution of Na+ between two compartments separated by a membrane that allows the free diffusion of Na+. Our findings demonstrated that changes in [Alb-]pw are linearly related to changes in [Na+]pw as predicted by Gibbs-Donnan equilibrium. However, based on our findings, we predict that the improvement in cirrhosis-associated hyponatremia due to intravascular volume depletion results predominantly from the restoration of intravascular volume rather than alterations in Gibbs-Donnan equilibrium.

Serum inosine, and symmetrical di‐methyl arginine (SDMA) concentrations were reduced at different time points when dogs were fed a controlled protein and phosphorus food with different fatty acid compositions

Dogs (43, 3.1 to 14.8 years of age) were assigned to one of three dietary treatment foods which was fed throughout the experiment in order to evaluate the effect of food on specific circulating metabolites. Dogs were analyzed for body composition and serum analyzed at 0, 1, 3 and 6 months. Serum analysis included urea, albumin, fatty acids, inosine and SDMA. The experimental protocol was reviewed and approved by the Institutional Animal Care and Use Committee. All foods contained approximately 14% protein and 18% fat. Fatty acid composition was as follows: Food 12:0 18:2 n6 18:3 n3 20:5 n3 22:6 n3 Control (C) 0.01 3.07 1.27 0.01 0.0 C + fish oil (CFO) 0.01 3.09 1.35 0.10 0.07 CFO + coconut oil (CFOCO) 0.87 4.61 1.63 0.23 0.17 Serum fatty acid concentration increased in response to increased intake throughout the study. There was no change in albumin concentration or lean body mass. There was a decrease in serum urea nitrogen and inosine after one month and through the rest of the study (P&lt;0.05). There was no change in SDMA at one month but a significant decrease (P&lt;0.05) through the rest of the study. The finding that SDMA was not different at one month while urea, inosine and the fatty acids mentioned above were all changed suggests that SDMA was controlled through a different function, reflecting an adaption to the dietary intake rather than a mass action response.This research was supported by Hill's Pet Nutrition and IDEXX Laboratories.

Changes in imatinib plasma trough level during long-term treatment of patients with advanced gastrointestinal stromal tumors.

306 Background: Pharmacokinetic study in patients with gastrointestinal stromal tumors (GISTs) suggested that plasma concentrations of imatinib decrease following long-term exposure. We therefore measured changes in imatinib plasma trough levels (Cmin) after long-term exposure. Methods: Between November 2009 and May 2010, follow-up (FU) imatinib Cmin was measured in 65 patients who received the same dose of imatinib for at least 9 months after a previous baseline (BL) measurement. Total 244 blood samples were obtained (127 at BL and 117 at FU) and plasma level was measured by liquid chromatography-tandem mass spectrometry. Results: Median patient age was 54 years (range, 28–76 years) and 42 (64.6%) patients were male. Sixty-one (93.8%) patients were treated with 400 mg/day imatinib and 4 (6.2%) with 300 mg/day. The median interval from initiation of imatinib to BL test was 6.4 months (range, 0.5–66.6 months), and the median interval between BL and FU test was 13.1 months (range, 9.6–18.4 months). The mean ± standard deviation imatinib Cmin was significantly higher at FU than at BL (1442 ± 693 ng/mL vs 1221 ± 624 ng/mL, p&lt;0.001). The mean inter- and intra-subject variabilities were 49.2% and 25.5%, respectively, at BL, and 44.2% and 20.4%, respectively, at FU. Multivariate analysis showed a significant correlation between the ratio of FU to BL imatinib Cmin and that of albumin (r=-0.397, p=0.001). In per-sample analysis, imatinib Cmin was significantly correlated with age, hemoglobin, albumin, creatinine clearance, previous major gastrectomy and time between initiation of imatinib and plasma level tests. Conclusions: Steady-state imatinib Cmin did not decrease but remained stable in most GIST patients during long-term treatment. Changes in imatinib Cmin were associated with changes in albumin concentration. Monitoring of imatinib Cmin only for concerns about time-dependent decreases in imatinib exposure is not necessary. [Table: see text]

Changes in imatinib plasma trough level during long-term treatment of patients with advanced gastrointestinal stromal tumors: correlation between changes in covariates and imatinib exposure

A pharmacokinetic study in patients with gastrointestinal stromal tumors (GIST) suggested that imatinib plasma concentration may decrease following long-term exposure. We assessed changes in imatinib plasma trough levels (C(min)) during long-term treatment. Follow-up (FU) imatinib C(min) was measured in 65 patients who received the same dose of imatinib for at least 9 months after previous (initial) tests. After exclusion of 7 patients who had been treated with imatinib for over 2 years at the time of initial testing, 58 patients were included in this analysis. The median intervals from initiation of imatinib to initial testing and from initial to FU testing were 5.5 months (range, 0.5-24.0 months) and 13.0 months (range, 9.6-17.9 months), respectively. Mean inter- and intra-subject variability values were 47.7% and 20.9%, respectively, at initial measurements, and 45.2% and 19.4%, respectively, at FU. Mean FU imatinib C(min) (1,370 ± 661 ng/mL) was significantly higher than mean initial C(min) (1,171 ± 573 ng/mL; p = 0.003). Compared with initial C(min), FU C(min) was decreased in 22 patients and increased in 36, with median changes of 13% and 32%, respectively. Multivariate analysis showed a significant correlation between the ratio of FU to initial imatinib C(min) and that of albumin (r = -0.39, p = 0.003). During long-term treatment, imatinib C(min) did not decrease significantly but remained stable or increased in most patients. Changes in imatinib C(min) were associated with changes in albumin concentration. Monitoring of imatinib C(min) only for concerns about time-dependent increases in imatinib clearance is not necessary.

Administration of 5% human serum albumin in critically ill small animal patients with hypoalbuminemia: 418 dogs and 170 cats (1994-2008)

To describe the administration of 5% human serum albumin (HSA) in 588 critically ill hypoalbuminemic dogs and cats, and report outcome to discharge, changes in albumin concentration, and adverse effects during hospitalization. Retrospective clinical study. Private emergency and general veterinary center. Client-owned dogs and cats. None. The medical records of 588 critically ill hypoalbuminemic animals (418 dogs and 170 cats) were reviewed. All animals had hypoalbuminemia (serum albumin<20 g/L [2.0 mg/dL]) at admission, received an infusion of 5% HSA, and received no other colloid infusion. The HSA solution was administered through a peripheral vein at 2 mL/kg/h for 10 h/d (total volume 20 mL/kg/d) until albumin reached 20 g/L. The number of days of HSA infusion (median and range) was 4 days (2-11 d) for dogs and 3 days (2-7 d) for cats. Three hundred and sixteen dogs (75.6%) survived to discharge; 56 of 418 (13.4%) died in hospital. One hundred and twenty-three cats (72.3%) survived to discharge; 21 of 170 (12.4%) died in hospital. Severe hypersensitivity reactions such as anaphylaxis, angioedema, and urticaria were not noted. Interruption of albumin infusion and specific treatment of reactions were not required in any animal. In this study, administration of 5% HSA appeared to be safe in a large group of critically ill, hypoalbuminemic dogs and cats. The results should be interpreted with caution due to the retrospective, descriptive nature of the study, the absence of control groups and the lack of follow-up data, as well as the potentially life-threatening complications of HSA administration.

Ischaemia-modified albumin elevation after percutaneous coronary intervention reflects albumin concentration rather than ischaemia

Percutaneous coronary intervention (PCI) is accepted as a model of myocardial ischaemia in studies of ischaemia markers, especially of ischaemia-modified albumin (IMA). However, there is concern that IMA levels may reflect changes in albumin concentrations rather than myocardial ischaemia also during PCI. Twenty-one consecutive patients (17 men and 4 women) undergoing single-vessel percutaneous coronary angioplasty were enrolled in the study. IMA and albumin levels were measured together with myoglobin, creatine kinase 2 and cardiac troponin I, before (Group 1), immediately after (Group 2) and 6 h after (Group 3) the procedure of PCI. The IMA levels of Group 2 were significantly higher than those of Group 1 and Group 3 (P < 0.05 for both). However, correction of IMA by multiplying with the (individual albumin concentration of the patient/median albumin concentration of Group 1) ratio gave no statistical differences between the groups (P > 0.05). There were strong negative correlations between IMA levels and albumin concentrations within individual groups (r = -0.757, P < 0.001; r = -0.712, P < 0.001; and r = -0.705, P < 0.001 for Group 1, Group 2 and Group 3, respectively). The results confirm the close dependency of IMA results on albumin concentrations. Therefore, IMA results reflect albumin concentrations rather than myocardial ischaemia also in PCI. This situation and lack of standard reference materials for the albumin cobalt binding assay can lessen the diagnostic performance of IMA.

Effect of the duration of commercial journeys between rearing farms and growing–finishing farms on the physiological stress response of weaned piglets

To find the effect of journey duration on the stress levels of weaned piglets a combination of physiological welfare indicators was used. One hundred and thirty-six piglets were monitored in two replicates of a short (0.6 h) and a long (8.3 h) commercial transport from a rearing to a growing–finishing farm. Variables studied were haematocrit, red blood cell count (RBC), total white blood cell count (WBC), differential WBC counts, serum pig's major acute phase protein (Pig-MAP), haptoglobin (Hp), cortisol, glucose, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), total protein, and albumin before loading and immediately after unloading. A marked increase in leucocytes ( P < 0.01) and a tendency to lower eosinophil concentrations ( P = 0.086) were observed in those piglets transported during the short journeys. On the other hand, the decrease in lymphocytes was particularly remarkable in the long journeys ( P < 0.01). No increase in Hp concentrations after the transports was found, but an increase in Pig-MAP concentrations was observed at the end of the long journeys ( P < 0.001). Cortisol concentrations did not show significant changes in either short or long journeys. According to CPK ( P < 0.05) and LDH activities, some physical fatigue was detected at the end of transports, particularly in the short journeys. The decrease in haematocrit values in the short journeys ( P < 0.05), and the absence of variations in RBC, albumin, and total protein concentrations would indicate that the loss of body water during both transport durations was reduced. Sex did not affect the response of piglets to transport, which could be attributable to the young age of the animals. Changes in albumin concentrations ( P < 0.05), together with the tendencies to higher WBC ( P = 0.092) and neutrophil counts ( P = 0.076), suggest a more marked response to the stress of transport in heterozygous for the halothane gene ( Nn) piglets than in homozygous negative ( NN) piglets. Overall results indicate that, although transports were generally stressful, it is unclear which of the two durations was more detrimental for piglet welfare, and suggest a different stress response to transport with respect to that of older pigs.