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PubMed1997

Evidence of differential renal dysfunctions during exercise in men.

Post-exercise proteinuria is a common phenomenon in healthy subjects. Previous studies have used albumin (Alb) and beta 2-microglobulin (beta 2-m) molecules as representatives of high- and low-molecular-weight proteins. Recently, more specific markers of the human kidney proximal tubule have been used to identify the precise site of alterations. Active male subjects underwent two strenuous runs, one 400-m run and one 3000-m run. Urine was collected from the subjects before and after each event. Total protein (TP), Alb, alpha 1-microglobulin (alpha 1-m), beta 2-m, intestinal alkaline phosphatase (IAP), tissue-nonspecific alkaline phosphatase (TNAP) and N-acetyl-beta-D-glucosaminidase (NAG) were determined for each sample. The short-distance run (400 m) resulted in the largest increases (P < or = 0.05) in TP (31-fold), Alb (100-fold) and beta 2-m (164-fold) as compared to the long-distance run (3000-m). The alpha 1-m excretion rates were increased to a lesser extent by the exercises. The IAP activity was slightly increased (+90%) by the 400-m run while the TNAP and NAG activities showed a 6.8-fold and a 3.6-fold increase, respectively, after this event. Smaller increases were recorded for the long-distance run (P = 0.05). To conclude, the present investigation showed that: (1) post-exercise proteinuria is related to the absolute intensity of exercise; (2) the impairment of protein reabsorption is revealed better by changes in Alb and beta 2-m; (3) changes in TNAP and NAG activities could reveal biochemical modifications that occur in the proximal tubule, particularly at the S1-S2 segment.

Adult↗
PubMed2005

Albumin-producing hepatocytes derived from cryopreserved F344 rat bone marrow cells transplanted in the livers of congenic Nagase's analbuminemic rats.

PURPOSE: Hematopoietic stem cells (SCs) are thought to have the potential to differentiate into hepatocytes; however, this potential has not been reported for cryopreserved SCs. We investigated whether cryopreserved bone marrow cells (BMCs) from F344 rats (F344) can induce the growth of albumin-producing hepatocytes in the livers of congenic Nagase's analbuminemic rats (F344alb). METHODS: F344 BMCs were cryopreserved in University of Wisconsin (UW) solution containing 10% fetal bovine serum and 12% dimethylsulfoxide, at -80 degrees C. After thawing, 20 x 10(6) cells were infused via the portal vein into the livers of F344alb immediately after 70% hepatectomy (PH). We examined the recipient livers for albumin-positive (alb+) hepatocytes and albumin mRNA, and measured the serum albumin levels 4 weeks later. RESULTS: Single and double alb+ hepatocytes were occasionally seen in the F344alb livers without the BMC transplantation. However, clusters consisting of more than three alb+ hepatocytes were seen in the livers of recipients transplanted with the cryopreserved BMCs after PH, the same as in the livers transplanted with freshly isolated BMCs. Normal albumin mRNA was detected in the recipient livers and the serum albumin levels were increased. CONCLUSION: Cryopreserved F344 BMCs can induce the growth of alb+ hepatocytes after transplantion in the F344alb liver after PH.

Albumins↗
PubMed1992

Cardiomyocytes express albumin binding proteins.

We investigated whether cardiomyocytes express specific albumin binding proteins (ABP) which may function in the dissociation of fatty acids from their non-covalent complexes with albumin. The experiments were performed on rat neonatal cardiomyocytes (freshly isolated and up to 3 days in culture) and on an enriched sarcolemmal fraction isolated from adult rabbit ventricular myocardium. Three types of experiments were conducted: (a) identification of ABP on electroblots of cardiomyocytes and sarcolemmal extracts reacted with [125I]-bovine serum albumin ([125I]Alb); (b) kinetic assays of [125I]Alb interaction with cardiomyocytes (at 37 degrees C), and with a sarcolemmal fraction (at 4 degrees C); (c) affinity isolation of ABP from solubilized radioiodinated sarcolemmal proteins interacted with an albumin-agarose matrix. The investigation showed that: first, two pairs of polypeptides (ABP of M(r) 18 and 31 kDa) in either cardiomyocytes or sarcolemmal fraction reacted on electroblots with [125I]Alb; second, the binding of the latter to cardiomyocytes was saturable and competed by unlabeled albumin: 50 microM albumin reduced by approximately 90% the binding of radiolabeled albumin. The sarcolemmal fraction bound [125I]Alb with a Kd of 3.66 x 10(-7) M. Thirdly, among the sarcolemmal proteins retained by the albumin-agarose matrix (18 and 31 kDa), the most prominent was the lower band (approximately 16 kDa) of the 18 kDa pair of ABP. The observations revealed that albumin interacts with relatively high affinity with specific binding sites on cardiomyocyte sarcolemma. This interaction may be a recognition step for subsequent fatty acid dissociation and translocation.

Albumins↗
PubMedDate not supplied

Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia.

Plasma and cerebrospinal fluid (CSF) from 20 patients with Alzheimer's dementia or senile dementia of Alzheimer type (AD/SDAT), 23 with multi-infarct dementia (MID) and 16 controls were assayed for their content of immunoglobulins (Ig) and albumin (Alb). The concentrations of IgG and Alb were used to analyze the blood-CSF barrier function in the respective group. MID patients had significantly (P less than 0.001) elevated plasma IgG levels compared to controls and AD/SDAT patients. CSF concentration of Alb was significantly higher in MID (P less than 0.01) and AD/SDAT (P less than 0.05) patients compared to the controls. Concentration of CSF IgG was significantly (P less than 0.05) lower in AD/SDAT patients compared to the MID patients; no significant differences were found when CSF concentrations of IgG of demented patients were compared to controls. These findings may indicate a blood-CSF barrier dysfunction especially in cases with MID with significantly (P less than 0.001) elevated values of transudation. Also these findings indicate a non-specific and/or specific binding of IgG in CNS tissue and/or vessel walls in both forms of dementia on the basis of low IgG ratios compared to proportionally higher Alb ratios. There were no signs of local synthesis of IgG in CNS in either group of demented patients.

Aged↗
PubMed1995

Total serum protein and serum protein fractions in depression: relationships to depressive symptoms and glucocorticoid activity.

Recently, it has been reported that major depression is accompanied by changes in plasma protein concentrations indicative of an acute-phase protein (APP) response. The purpose of the present study was to examine total serum protein (TSP) and the electrophoretically separated major fractions of serum proteins (SP), i.e., albumin (Alb), alpha 1, alpha 2, beta and gamma globulin, in depression. Highly significant differences were found in TSP and the separated SP fractions between major depressed patients and normal controls and between melancholic and minor depressed patients. Major depressed subjects showed significantly lower TSP and Alb concentrations and a higher percentage of the alpha 1 globulin fraction than normal controls and minor depressed subjects. Major depressed subjects had significantly higher and lower percentages, respectively, of alpha 2 and gamma globulin fractions than normal controls. In depressed subjects, there were significant negative correlations between TSP or Alb concentrations and severity of illness. Psychomotor retardation and anorexia were psychopathological correlates of lower TSP and Alb concentrations while middle insomnia and psychomotor retardation were related to changes in the alpha 2 globulin fractions. Basal plasma cortisol values were significantly and positively related to serum alpha 2 globulin. The results support the view that major depression is accompanied by an APP response.

Acute-Phase Proteins↗
PubMedDate not supplied

'Correction' of serum calcium values for albumin biased in geriatric patients.

Determination of serum ionized calcium concentration (Cal) is more tedious as a screening method than measuring serum total calcium concentration (CaT) and is not widely practicable. Thus, in clinical practice and even in research, it is customary to 'correct' the serum total calcium concentration (CaT) for that of albumin (Alb) to estimate the 'true' calcemic status,i.e. Cal. However, owing to confounding factors that are incompletely understood at present, the 'corrected' result is imprecise. The hypothesis of the present study was that in geriatric hypoalbuminemia, it could even be biased due to confounding factors associated with aging and related to the Alb level itself. To test this hypothesis, CaT, Alb and Cal were measured in 558 consecutive geriatric in-patients with varying degrees of hypoalbuminemia. The lower the Alb level, the more strikingly the sensitivity of CaT for detecting low Cal was impaired by the correction. In geriatric hypoalbuminemia, the correction is not merely imprecise but even biased (inaccurate). The bias increases with the degree of hypoalbuminemia (i.e. with the need for correction) and leads to underdiagnosis of 'true' (ionic) hypocalcemia.

Journal Article↗
PubMed1993

Characteristics of a membrane-associated antilactogen binding site for tamoxifen.

The antilactogen binding site (ALBS) is a membrane associated protein to which tamoxifen (TAM) and related non-steroidal antiestrogens, but not estrogen, bind. It is through this site that TAM inhibits lactogen binding to the prolactin (Prl) receptor and subsequent Prl induced growth and differentiation in target tissues. Binding of lactogens to the Prl receptor is inhibited by TAM or 4-hydroxy-TAM at 4 degrees C as well as room temperature, thus suggesting that the ALBS is not an enzyme. TAM acts by inhibiting the binding of lactogens to the receptor rather than promoting dissociation of the hormone-receptor complex. Lactogens bind to mammary gland membranes with an Kd of 4.3-8.2 x 10(-10) M. In the presence of 10(-7) M TAM the affinity decreased to a Kd of 0.8-1.6 x 10(-9) M. Binding of 3H-TAM to mammary gland membranes was effectively inhibited by an anti-Prl receptor antibody, thus suggesting a close relationship between the Prl receptor and the ALBS. Separate affinity purification of the ALBS and the Prl receptor resulted in peak fractions demonstrating specific binding activity for both TAM and lactogenic hormones. Re-isolation of the affinity purified Prl receptor on a TAM-Sepharose affinity resin again resulted in co-elution of both binding activities. The isolates from both affinity resins contained primarily a single band with an apparent molecular mass of 90 kDa. This band was precipitated with the anti-Prl receptor antibody and specifically bound the affinity label ring-3H-TAM aziridine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Glomerular permeability defect in hypertension is dependent on renin angiotensin system activation.

BACKGROUND: The aim of the present study was to compare glomerular permeability alterations associated with experimental hypertension models known to have different effects on the circulating renin-angiotensin system (RAS). METHODS: Five groups, 10 animals each, were studied. One group served as a nonhypertensive control. The other four groups of hypertensive animals were composed of spontaneously hypertensive rats, deoxycorticosterone acetate hypertensive rats, Goldblatt two-kidney, one-clip rats, and a group of Wistar rats infused with angiotensin II (200 ng/kg/min). Tail-cuff sphygmomanometric systolic blood pressure (BP), albumin permeability determined in isolated glomeruli exposed to oncotic gradients (P(alb)), glomerular filtration rate (GFR, iopamidol method), plasma renin activity (PRA), and albuminuria were evaluated. RESULTS: Alterations in P(alb) and albumin excretion rate were more evident in the experimental models with an activation of the RAS despite similar levels of systolic BP and GFR. A positive correlation was found between P(alb) and albuminuria (r = 0.51; P < .001) and between systolic BP and albuminuria (r = 0.37; P < .01). No relation was found between systolic BP and P(alb). CONCLUSIONS: The present study indicates that the activation of the RAS plays a significant role in the development of glomerular albumin permeability defects in hypertensive models and may contribute to the mechanisms that lead to target organ damage in hypertension.

Albumins↗
PubMed2005

Rat sinusoidal liver endothelial cells (SECs) produce pro-fibrotic factors in response to adducts formed from the metabolites of ethanol.

Previous studies with alcohol-associated malondialdehyde-acetaldehyde (MAA)-modified proteins have demonstrated an increase in the expression of adhesion molecules, and the secretion of pro-inflammatory cytokines/chemokines by rat sinusoidal liver endothelial cells (SECs). However, no studies have been initiated to examine the effects of MAA-modified proteins on the expression of the extracellular matrix (ECM) protein, fibronectin and its isoforms. For these studies, SECs were isolated from the liver of normal rats, and exposed to MAA-modified bovine serum albumin (MAA-Alb). At selected time points, the total plasma and cellular fibronectin were determined by Western blot. Injection of rat liver via the mesenteric vein with MAA-Alb was performed in an effort to evaluate the potential in vivo role of MAA-modified proteins in the development of fibrosis. Expression of both plasma and cellular fibronectin was significantly increased over controls in the MAA-Alb stimulated SECs (>3-fold). Importantly, the isotype of fibronectin secreted was determined to be of the EIIIA variant and not EIIIB. These data were confirmed using RT-PCR procedures on liver tissue from; isolated SECs, and from an in vivo animal model wherein MAA-Alb was administered via the mesenteric vein. Thus, these studies demonstrate that MAA-modified proteins initiate a pro-fibrogenic response by initiating the expression of the fibronectin EIIIA isoform by SECs.

Alternative Splicing↗
PubMed2004

Colonization of albumin-producing hepatocytes derived from transplanted F344 rat bone marrow cells in the liver of congenic Nagase's analbuminemic rats.

BACKGROUND/AIMS: We investigated whether bone marrow cells (BMCs) of normal rats can be transformed in albumin-producing hepatocytes in analbuminemic rat livers. METHODS: BMCs (2 x 10(7)) from F344 rats (F344) were infused via the portal vein into the livers of congenic Nagase's analbuminemic rats (F344alb) immediately after 70% hepatectomy (PH). Alternatively, F344alb were hematopoietically reconstituted with F344 BMCs by whole body irradiation and BMC transplantation before PH. The recipients were examined for albumin positive (alb +) hepatocytes and albumin mRNA in the livers as well as serum albumin levels 4 weeks later. Sry3 in situ hybridization was done for the livers of female F344alb that received male F344 BMCs. RESULTS: Livers of untreated F344alb contained a few single and double alb+hepatocytes, but these did not form clusters after PH. Clusters (>3 alb + hepatocytes) were detected in livers of the recipients which were transplanted with BMCs immediately after PH as well as the reconstituted F344alb with or without PH. Normal albumin mRNA was detected in the recipient livers, and serum albumin levels were increased. Sry3 was identified in the alb+clusters in the female recipients. CONCLUSIONS: Transplanted BMCs from normal rats can increase clusters of albumin-producing hepatocytes within the liver of analbuminemic rats.

Albumins↗
PubMed2004

Hepatocytes derived from peripheral blood stem cells of granulocyte-colony stimulating factor treated F344 rats in analbuminemic rat livers.

BACKGROUND: hematopoietic stem cells (SCs) mobilized from the bone marrow (BM) into peripheral blood (PB) are reported to have ability to differentiate into various cell types. We investigated whether PB-SCs mobilized by treatment with granulocyte-colony stimulating factor (G-CSF) in normal rats can raise albumin-producing hepatocytes after transplantation within the liver of analbuminemic rats. MATERIALS AND METHODS: Fischer 344 rats (F344) were used as donors, and F344 congenic Nagase's analbuminemic rats (F344alb) as recipients. The donors were repeatedly treated with human recombinant G-CSF, and their PB mononuclear cells (MNCs) were infused into the portal veins of recipients immediately after 70% hepatectomy (PH). RESULTS: Although a few single and small clusters (less than five cells) of albumin positive (alb+) hepatocytes were seen in the livers of untreated F344alb and of the animals undergoing PH alone or transplantation of PB-MNCs with or without the prior G-CSF treatment, clusters consisting of more than 6 alb+ hepatocytes were only detected in the livers of recipients that received transplantation of mobilized PB-MNCs or BM-MNCs under the regenerating condition induced by PH. Sry3, a Y chromosome marker, could be detected corresponding to the alb+ clusters by in situ hybridization when male donors and female recipients were used. Moreover, normal albumin gene sequences were demonstrated in the microdissected alb+ clusters by polymerase chain reaction, and the serum albumin levels were elevated in the recipients. CONCLUSIONS: Hematopoietic SCs mobilized from BM into PB by the G-CSF treatment may raise hepatocyte colonies, when transplanted into regenerating livers.

Animals↗
PubMed2005

Cold-induced fluid extravasation during cardiopulmonary bypass in piglets can be counteracted by use of iso-oncotic prime.

OBJECTIVE: Hypothermic cardiopulmonary bypass is associated with increased fluid extravasation. This study aimed to compare whether iso-oncotic priming solutions, in contrast to crystalloids, could reduce the cold-induced fluid extravasation during cardiopulmonary bypass in piglets. METHODS: Three groups were studied: the control group (CT group; n = 10), the albumin group (Alb group; n = 7), and the hydroxyethyl starch group (HES group; n = 7). Prime (1000 mL) and supplemental fluid were acetated Ringer solution, 4% albumin, and 6% hydroxyethyl starch, respectively. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (cooling to 28 degrees C within 15 minutes) was initiated and continued to 90 minutes. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit levels, and tissue water content were recorded, and protein masses and fluid extravasation rates were calculated. RESULTS: Colloid osmotic pressure in plasma decreased immediately after the start of cardiopulmonary bypass in the CT group but remained stable in the Alb and HES groups. Colloid osmotic pressure in interstitial fluid tended to decrease in the CT group and remained unchanged in the Alb group, whereas a slight increase was observed in the HES group. Immediately after the start of cooling, fluid extravasation rates increased from 0.15 +/- 0.10 to 0.64 +/- 0.12 mL . kg -1 . min -1 in the CT group, whereas no such increase was observed in the Alb and HES groups. The changes in fluid extravasation rates were reflected by corresponding changes in tissue water content. CONCLUSION: The use of albumin or hydroxyethyl starch as prime to preserve the colloid osmotic pressure during cardiopulmonary bypass causes a reduction in the cold-induced fluid extravasation compared with that seen with crystalloids. Albumin seems more effective than hydroxyethyl starch to limit cold-induced fluid shifts during cardiopulmonary bypass.

Albumins↗
PubMed2004

Long-lasting, selective, anxiogenic effects of feline predator stress in mice.

Lasting increases in anxiety-like behavior (ALB) are produced by brief exposure of rats to a cat [Adamec RE, Shallow T, Lasting effects on rodent anxiety of a single exposure to a cat, Physiol. Behav., 54 (1993) 101-109.]. Mice also respond defensively to natural predator stimuli. Moreover, chronic exposure of mice to rat odor has immediate anxiogenic effects in plus maze and lasting (7 days) and effects on acoustic startle. The present study examined the lasting (7 days) after effects on ALB of a brief unprotected exposure of male CFW mice to a cat. Lasting effects on ALB of exposure to the cat exposure room were also assessed. Effects on behavior were studied in the hole board and elevated plus-maze (EPM). An ethological analysis of behavior revealed that risk assessment in the EPM was increased the most in predator-stressed mice. Mice exposed to the cat exposure room showed increased risk assessment falling between controls and cat exposed mice. Behavior in the hole board was unaffected, as were most other behaviors in the plus maze. Factor analysis revealed independence of risk assessment from other measures of ALB, activity and exploration, consistent with findings in rats. Aspects of the stress experience were highly predictive of later response to the cat. Cat biting and pawing, mouse fleeing and mouse weight measured at the time of cat exposure together accounted for 71% of the variance of risk assessment in cat exposed mice. The significance of these findings for vulnerability to cat predator stress of mice and for the use of predator stress in mice as a model of aspects of posttraumatic stress disorder (PTSD) are discussed.

Animals↗
PubMed1997

Transmitter systems involved in neural plasticity underlying increased anxiety and defense--implications for understanding anxiety following traumatic stress.

Lasting changes in anxiety-like behavior (ALB) may be produced in several ways. These include partial limbic kindling, injection of the beta-carboline FG-7142, and brief, non-injurious, exposure of rodents to cats (predator stress). Both seizures and FG-7142 induce long-term potentiation (LTP) in efferent pathways of the amygdala known to participate in feline defensive behavior. By comparing the behavioral and physiological effects of partial kindling and injection of FG-7142, NMDA-dependent LTP in the right amygdalo-periacqueductal gray (PAG) pathway emerges as being critical to maintained increases in feline ALB. A similar dependence on NMDA-mediated processes is described for lasting increases in rodent ALB following predator stress. The lasting aftereffects of predator stress on a variety of measures parallel many of the symptoms of post-traumatic stress disorder (PTSD). Support is provided for the idea that behavioral changes following FG-7142 and predator stress may model anxiety associated with PTSD. Moreover, it is suggested that both models share mechanisms in common involving the PAG. These mechanisms likely involve initiation of LTP by NMDA receptors, and prolongation of LTP by CCKB receptors. To the extent that response to the stressors reviewed here mimics the symptoms of PTSD, the data implicate NMDA-mediated processes in the creation of what van der Kolk has called permanent emotional memories in PTSD. Their representation may be in the form of NMDA-dependent LTP of transmission within the amygdala and between the amygdala and its efferents. CCK may play a pivotal role in prolonging limbic LTP and anxiety following traumatic stress. Since block of CCKB receptors before and after the stressor prevents lasting increases in ALB, pharmacological intervention to block CCK receptors shortly after a traumatic stressor might be efficacious in mitigating the permanence of these emotional memories.

Aggression↗
PubMedDate not supplied

Peritoneal protein loss in patients with high peritoneal permeability: comparison between continuous ambulatory peritoneal dialysis and daytime intermittent peritoneal dialysis.

BACKGROUND: Dialysate protein loss is involved in the etiology of hypoalbuminemia and malnutrition on continuous ambulatory peritoneal dialysis (CAPD). Patients with high peritoneal membrane permeability had the lowest serum albumin (Alb) and highest dialysate protein concentrations and achieved higher small solute dialysis/plasma equilibration in a shorter time than patients with low peritoneal transport. The aim of this prospective crossover study was to evaluate whether protein loss might be decreased in patients with high peritoneal permeability on short dwell-time (DT) peritoneal dialysis. METHODS: Five high and nine high-average peritoneal transport patients were subjected to the following sequential dialysis schemes (four exchanges/day, glucose 1.5%): scheme A, three daytime exchanges (4-6 h DT) and one nightly (8-12 h DT) for 2-3 days, scheme B, 3-h DT each and dry peritoneum at night during 5 days, a wash-out period similar to scheme A, and scheme C, 2-h DT each and dry peritoneum the remainder of day and night during 5 days. Dialysate Alb, IgG, IgA, and IgM losses and adequacy of dialysis were evaluated at the end of each scheme. RESULTS: Dialysate IgM was not detected. All protein losses were reduced with the short DT dialysis schemes; however, dialysis CCl and KT/V(urea) were also decreased. In patients with high peritoneal transport type, the 3-h DT dialysis scheme achieved a reduction in Alb loss without significant reduction of adequacy of dialysis. CONCLUSIONS: Peritoneal Alb, IgG, and IgA losses are significantly reduced in patients with high peritoneal permeability on short dwell-time dialysis and extended dry periods. However, a reduction of dialysis contribution to small solute clearances was also observed, Three-hour dwell-time dialysis may be particularly useful in patients with high peritoneal transport type, as it tends to reduce peritoneal protein loss without notably reducing adequacy of dialysis.

Adult↗
PubMed1996

Benzodiazepine receptor stimulation blocks scopolamine-induced learning impairments in a water maze task.

Central cholinergic (ACh) blockade produces profound cognitive impairments in human and animal subjects. Our previous research demonstrated that ACh blockade exacerbates stress-induced adrenocorticotrophin (ACTH) and corticosterone (CORT) secretion, and increases anxiety-like behavior (ALB) in rats. The fact that all these responses occur following the same manipulation led us to question whether or not increases in ALB might play a part in the cognitive deficits. This issue was all the more intriguing given that anxiolytic agents such as benzodiazepines are reported to produce learning and memory impairments on their own. We reasoned that a low dose of diazepam (DZP) with no apparent cognitive effects itself, might be able to antagonize an impairment induced by scopolamine (SCOP). Adult male Lister rats (n = 6/group) were administered IP either vehicle (VEH), 0.5 mg/kg DZP, 0.25 mg/kg SCOP, or 0.5 mg/kg DZP, followed 20 min later by 0.25 mg/kg SCOP, and tested 20 min later in a water maze for latency to locate a hidden platform and for path length taken to the platform. Rats were tested in an acquisition phase (Day 1) and a retention phase (Day 2), as well as on a visually guided task. On Day 1, SCOP produced a marked acquisition deficit that was unaffected by DZP. DZP by itself had no obvious effect. However, whereas SCOP resulted in a persistent deficit on the retention task (Day 2), pretreatment with DZP prior to SCOP on Day 1 completely abolished the impairment. There were no group differences on the visually cued task. We contend that SCOP-induced cognitive deficits may, in part, be due to increases in ALB. Stimulation of benzodiazepine receptors may offset the loss of cholinergic systems underlying consolidation mechanisms, but not those mediating immediate task performance. Whether this effect of DZP relates to an action on ALB remains to be elucidated.

Animals↗
PubMed2002

Non-linear production of benzene oxide-albumin adducts with human exposure to benzene.

Benzene is initially metabolized to benzene oxide, which either undergoes further metabolism or reacts with macromolecules including proteins. Previously reported levels of benzene oxide-albumin adducts (BO-Alb) are analyzed from 30 workers exposed to 0.2-302 ppm benzene and 43 controls from Shanghai, China. Although both exposed workers and controls had significant levels of BO-Alb in their blood, exposed subjects' adduct levels (GM=378 pmol/g protein) were much greater than those of controls (GM=115 pmol/g protein). When the natural logarithm of the BO-Alb level was regressed upon the natural logarithm of exposure among the 30 exposed subjects, a strong effect of benzene exposure was observed (R(2)=0.612; p<0.0001). Because the slope of the relationship between BO-Alb and benzene exposure was significantly less than one in log-space, we infer that production of benzene oxide was less than proportional to benzene exposure. Since benzene is a substrate for CYP2E1, these results are consistent with saturation of CYP450 metabolism. They indicate that deviations from linear metabolism began at or below benzene exposures of 10 ppm and that pronounced saturation was apparent at 40-50 ppm. To our knowledge, this is the first study to investigate the linearity of human metabolism of a carcinogen based upon protein adducts.

Albumins↗
PubMed1997

Detection of a genetic variant, lysine-->glutamic acid at position 372 of human serum albumin, by capillary electrophoresis and structural identification.

A genetic variant of human serum albumin (alloalbumin) is detected by capillary electrophoresis (CE). Two albumin peaks, which were in the ratio of approximately one, were clearly separated. One of the peaks had the same migration time as normal albumin (Alb A) and the other (Alb X) had a longer migration time. SDS-polyacrylamide gel electrophoresis of CNBr fragments (CB) of Alb X indicated that the amino acid substitution was localized in the CB5 fragment (residue 330-446) of the molecule, because of anomalous migration of CB5 in the gel. The CE mapping of the tryptic peptides from the variant CB5 revealed clearly the existence of a new peptide, and the lack of two normal peptides. The sequence analysis of the variant peptide collected by CE micropreparation showed that the N-terminus of the variant peptide corresponded to that of T49 in Alb A. The substitution site, lysine-->glutamic acid at the position 372, was revealed by sequence determination of the variant peptide purified by reversed-phase HPLC.

Amino Acid Sequence↗