Higher Albumin Concentrations Research Articles

Regional variability in anaemia management and haemoglobin in the US.

Regional differences in haemoglobin values and process care measures were examined using data from the Centers for Medicare & Medicaid Services' End-Stage Renal Disease (ESRD) Clinical Performance Measures Project. It was posited that regional differences in haemoglobin values are consequent upon differences in components of clinical practice. A national random sample of 8336 adult, in-centre haemodialysis patients, stratified by the 18 regional ESRD Networks, was drawn. Information was collected for October-December 1998. Multivariable stepwise linear and logistic regression analyses were performed to identify variables associated with haemoglobin. Linear regression analysis was used to identify variables associated with Epo/Hb index (mean weight-adjusted treatment level erythropoietin (Epo) dose divided by mean haemoglobin). The percentage of patients with haemoglobin concentration < 11 g/dl ranged from 34 to 52% across ESRD Networks. In addition to haemoglobin there was significant, non-random variation among ESRD Networks with regard to prescribed Epo dose and administration route, intravenous (IV) iron prescription and dialyser flux (high flux = KUf > or = 20 ml/mmHg/h) (all P-values < 0.001). Higher haemoglobin was associated with older age, male gender, higher serum albumin, higher transferrin saturation, higher Kt/V, lower serum ferritin and lower prescribed Epo dose (all P-values < 0.01). Diabetes mellitus as cause of ESRD, high-flux dialyser use, IV iron prescription or subcutaneous Epo prescription were not associated with haemoglobin. Male gender, diabetes as cause of ESRD, older age, higher transferrin saturation and higher albumin concentrations were associated with lower Epo/Hb index. Prescription of IV iron and IV Epo were associated with higher Epo/Hb index. Regional mean haemoglobin levels vary considerably across the US and the variation in haemoglobin is explained by both non-modifiable factors and modifiable clinical practice-derived variables.

Matrix effects in the analysis of biological matrices by axial view inductively coupled plasma optical emission spectrometry

We are reporting observations of positive and negative variations of emission line intensities during the determination of boron and titanium in biological matrices by axial view inductively coupled plasma optical emission spectrometry with segmented charge-coupled device detection. The study included the testing of several elements (yttrium, palladium and platinum) and analytical wavelengths for internal standardization, aiming to compensate for variations in signal recovery due to matrix interferences. Human albumin was chosen as principal matrix component to assess the effect of variable chemical and instrumental operating conditions on boron response. A parametric study was performed by considering the application of two different nebulizer–aerosol chamber systems, the effect of plasma operating conditions on analyte and internal standard signals and the influence of common blood plasma electrolytes, added as salts of alkaline or alkaline earth elements. The pneumatic injection systems tested were a standard cross-flow nebulizer with a Scott type spray chamber and a concentric Meinhard type device coupled to a glass cyclonic spray chamber. The change from standard (i.e. medium RF power and relatively high aerosol carrier gas flow rate) to robust (i.e. higher RF power and lower carrier gas flow rate) conditions contributed to large, non-correlated variations in boron intensities and in some of the analyte/internal standard ratios. Significant memory effects were observed for injection of boron solutions prepared with boric acid and containing small amounts of acid, but those effects were negligible when the boron carrier compound was boronophenylalanyne. The injection of titanium solutions did not produce analyte carry-over effects. When internal standards were employed, a less effective signal compensation was consistently observed for boron at higher albumin concentrations when the difference in energies of the lines was between 4.5 and 6 eV. This effect was enhanced for some line pairs when robust conditions are employed. Differences in the response between nebulizers were minor, with a slight advantage in sensitivity for the cross-flow/Scott system. Yttrium was found to be useful for signal compensation in the determination of boron and titanium in blood and human plasma provided that the equivalent concentration of albumin in the nebulized sample dilutions was kept below 0.2% w/v. Simultaneous measurement of a reference strontium line was found to be useful as an additional verification of the response of yttrium as internal standard.

Albumin, steroid hormones and the origin of vertebrates.

Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and various phytochemicals and xenobiotics that bind to receptors for steroids and other lipophilic hormones. Despite albumin's low affinity (K(d) approximately 10(-4) M to 10(-6) M) for these lipophilic compounds, the high concentration of albumin in serum makes this protein a major carrier of steroids and lipophilic hormones and a regulator of their access to receptors. Albumin also functions as a sink for xenobiotics, diminishing the binding of xenobiotics to hormone receptors and other cellular proteins. This protects animals from endocrine disruption by xenobiotics. We propose that these properties of albumin were important in protochordates and primitive vertebrates, such as jawless fish, about 600 to 530 million years ago, just before and during the Cambrian period. It is at that time that the ancestral receptors of adrenal and sex steroids - androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins - arose in multicellular animals. Albumin regulated access of steroids to their receptors, as well as protecting animals from endocrine disruptors, such as phytochemicals, fungal chemicals and phenolics, and other chemicals formed at hydrothermal vents by geochemical processes. Thus, animals in which albumin expression was high had a selective advantage in regulating the steroid response and avoiding endocrine disruption by xenobiotics.

Protein overload-induced NF-kappaB activation in proximal tubular cells requires H(2)O(2) through a PKC-dependent pathway.

Abnormal traffic of proteins through the glomerular capillary has an intrinsic toxicity that results in tubular dysfunction and interstitial inflammation. It has been previously shown that in porcine proximal tubular cells high concentrations of albumin activated NF-kappaB, which is responsible for the enhanced synthesis of the inflammatory chemokine RANTES. This study investigates whether reactive oxygen species (ROS) served as second messengers in protein overload-induced NF-kappaB activation. Human proximal tubular cells (HK-2) were incubated (5 to 60 min) with human albumin and IgG (1 to 30 mg/ml). Both proteins induced a rapid or significant increase in hydrogen peroxide (H(2)O(2)) production at 5 min and persisting at 60 min. This effect was dose-dependent. The contribution of H(2)O(2) in regulating NF-kappaB activation was evaluated by using the antioxidants dimethyl-thiourea and pyrrolidine dithiocarbamate in protein-overloaded HK-2 cells. Both agents, by preventing H(2)O(2) generation, induced human albumin or IgG inhibited NF-kappaB activation. Stimulation of HK-2 with exogenous H(2)O(2) resulted in the activation of a NF-kappaB subunit pattern similar to that obtained after protein challenge. Specific inhibitors of protein kinase C (PKC) activity significantly prevented H(2)O(2) production and consequent NF-kappaB activation, suggesting that ROS generation in HK-2 cells occurs downstream of PKC activation. Either antioxidants or PKC inhibitor almost completely abolished the upregulation of the monocyte chemoattractant protein-1 gene induced by excess albumin, as evaluated by real-time PCR, thus supporting a role for PKC and ROS as critical signals for the expression of NF-kappaB-dependent inflammatory genes. To identify the enzymatic sources responsible for the increased H(2)O(2) production, the effect of dyphenyleneiodonium, an inhibitor of the membrane NADP(H) oxidase, was studied, as was the effect of rotenone, which blocks complex I of the mitochondrial respiratory chain. It was found that both agents significantly reduced the exaggerated H(2)O(2) induced by protein overload. These data indicate that exposure to excess proteins in proximal tubular cells induces the formation of ROS, which are responsible for NF-kappaB activation and consequent induction of NF-kappaB-dependent inflammatory signals.

Determinants of further survival in centenarians

Background:The purpose of the present paper was to study the impact of selected clinical and demographic variables on further survival in subjects over 100 years old.Methods:In 1992 the authors assessed activities of daily living, cognitive function, and nutritional status in 38 centenarians (seven men and 12 women living in the Tokyo metropolitan area as well as three men and 16 women living in Aichi prefecture; mean age: 100.9 ± 1.6 years). Survival data were recorded until 1996. Cox proportional hazard regression analysis was used to identify variables influencing likelihood of further survival in centenarians.Results:In 1996 21 subjects had died and 17 were still living. Of the 38 subjects, nine had illnesses at initial evaluation such as hypertension or other cardiovascular disease. Centenarians with a high cognitive level tended to have a high (independent) activities of daily living (ADL) score and/or a good nutritional condition. Cognitive levels were higher in men than in women. Cox proportional hazard regression analysis indicated that a high ADL score, a high level of cognitive function, or nutritional status tended to be advantageous for further survival in centenarians. Of the three parameters, after adjustment for clinical variables, only a high serum albumin concentration was a significant factor favoring survival in centenarians (hazard ratio: 0.44 for a 1‐SD increment in serum albumin concentration; 95% confidence interval: 0.23–0.85). The presence of illness, the age in 1992, or gender was not related to mortality risk in centenarians.Conclusion:Undernourishment jeopardizes survival even in late life.

Affinity of Human Serum Albumin for Bilirubin Varies with Albumin Concentration and Buffer Composition: RESULTS OF A NOVEL ULTRAFILTRATION METHOD

Albumin binding is a crucial determinant of bilirubin clearance in health and bilirubin toxicity in certain disease states. However, prior attempts to measure the affinity of albumin for bilirubin have yielded highly variable results, reflecting both differing conditions and the confounding influence of impurities. We therefore have devised a method based on serial ultrafiltration that successively removes impurities in [(14)C]bilirubin until a stable binding affinity is achieved, and then we used it to assess the effect of albumin concentration and buffer composition on binding. The apparent binding affinity of human serum albumin for [(14)C]bilirubin was strongly dependent on assay conditions, falling from (5.09 +/- 0.24) x 10(7) liters/mol at lower albumin concentrations (15 microm) to (0.54 +/- 0.05) x 10(7) liters/mol at higher albumin concentrations (300 microm). To determine whether radioactive impurities were responsible for this change, we estimated impurities in the stock bilirubin using a novel modeling approach and found them to be 0.11-0.13%. Formation of new impurities during the study and their affinity for albumin were also estimated. After correction for impurities, the binding affinity remained heavily dependent on the albumin concentration (range (5.37 +/- 0.26) x 10(7) liters/mol to (0.65 +/- 0.03) x 10(7) liters/mol). Affinities decreased by about half in the presence of chloride (50 mm). Thus, the affinity of human albumin for bilirubin is not constant, but varies with both albumin concentration and buffer composition. Binding may be considerably less avid at physiological albumin concentrations than previously believed.

Risk factors associated with development of postoperative ileus in horses.

To determine risk factors associated with development of postoperative ileus in horses undergoing surgery for colic. Case-control study. 69 horses that developed ileus after surgery for colic and 307 horses that did not develop postoperative ileus. Signalment, history, clinicopathologic data, treatment, lesions, and outcome were obtained from medical records. Variables associated with increased risk of postoperative ileus included age > 10 years, Arabian breed, PCV > or = 45%, high serum concentrations of protein and albumin, anesthesia > 2.5 hours' duration, surgery > 2 hours' duration, resection and anastomosis, and lesions in the small intestine. Enterotomy reduced the risk of postoperative ileus. After multivariate logistic regression, the final model included the variables Arabian breed, PCV > or = 45%, lesion type, duration of surgery (> 2 hours vs < or = 2 hours), and pelvic flexure enterotomy. Results suggest that by evaluating certain factors, horses at increased risk of postoperative ileus may be recognized before the condition develops. Preventative treatment and early intervention may be instituted in these horses. Shortening surgery time and performing an enterotomy may decrease the probability of horses developing postoperative ileus.

IMMUNOCHEMICAL CONTROL OF THE SPECIES ORIGIN OF INTESTINAL MUCOSA USED FOR HEPARIN PURIFICATION

Species specific antisera against bovine, ovine, and porcine serum albumin were produced in order to control the absence of bovine, ovine, or caprine tissues in the porcine intestinal mucosa used for heparin production. Two immunoassays were developed. An enzyme linked immunosorbent assay (ELISA) was very sensitive down to 1 ng/mL bovine albumin or 10 ppm bovine intestinal mucosa in porcine intestinal mucosa. For routine control, a more convenient single radial immunodiffusion assay (SRID) was found suitable to detect 2 μg/mL albumin or 3 p 1000 bovine, ovine, or caprine intestinal mucosa in porcine intestinal mucosa. Conditions of extraction of albumin from intestinal mucosa were optimized and a CV % of 4.1 was obtained for its quantitation. Due to higher albumin concentrations, detection of bovine hashed gut and lung was more sensitive (1.5and 0.9 p 1000, respectively). Using antisera raised against porcine albumin the SRID can be applied to certify the porcine origin of the intestinal mucosa used for heparin purification and to control its adequate conservation before analysis.

The influence of relative resistance and urea-supplementation on deliberate infection with Teladorsagia circumcincta during winter

The consequences for lambs of infection over the winter with Teladorsagia circumcincta were quantified by deliberate, trickle infection of selected animals at 7 months of age. Infected and control uninfected animals were each allocated into four groups, relatively resistant animals on a normal diet, relatively resistant animals on an isocaloric diet supplemented with urea, and relatively susceptible animals on the same two diets. Resistance and susceptibility was assessed by faecal egg counts following natural infection during the summer preceding the deliberate infection. During the deliberate infection egg counts remained low and most parasites recovered at necropsy were inhibited larvae. Nonetheless, infection reduced weight gain, decreased albumin and fructosamine concentrations and provoked a noticeable pepsinogen and eosinophil response. As most larvae were inhibited these responses may have been largely a consequence of immuno-inflammatory responses in the host rather than the direct action of parasites themselves. Relatively resistant animals on the supplemented diet allowed fewer larvae to establish and had higher fructosamine concentrations, higher albumin concentrations and decreased pepsinogen responses. Therefore, a combination of relatively resistant sheep and nutritional supplementation appears most efficient at controlling infection.

Peritoneal Transport Characteristics, Comorbid Diseases and Survival in CAPD Patients

To evaluate the influence of initial peritoneal transport rate, serum albumin concentration, and comorbid diseases on continuous ambulatory peritoneal dialysis (CAPD) patient survival. A prospective single-center study with a long-term follow-up. A total of 213 consecutive CAPD patients, who underwent a peritoneal equilibration test (PET) at a mean of 7 days (range 3 - 30 days) after beginning CAPD, were included in this study. One hundred twenty patients were male, 116 patients had comorbid diseases, and mean age was 49.5 years (range 18 - 76 years). A modified PET was performed using 4.25% glucose dialysis solution. Based on the dialysate-to-plasma creatinine concentration ratio at 4 hours' dwell (D4/P4 Cr, 0.62 +/- 0.14), patients were divided into high (H), high-average (HA), low-average (LA), or low (L) transporters. Of 213 patients, 16.9% were classified as H transporters, 30.5% as HA, 36.6% as LA, and 16.0% as L transporters. The H transporter group had a higher proportion of men, higher proportion of patients with comorbid diseases, lower initial serum albumin concentration, lower D4/D0 glucose, and lower drained volume. The initial D4/P4 Cr correlated with initial serum albumin (r= -0.35, p < 0.001). The patients with comorbid diseases had lower initial serum albumin and higher initial D4/P4 Cr. On Kaplan-Meier analysis, 2-year patient survival of group H was significantly lower compared to the other groups combined (57.1% vs 79.5%, p = 0.009). On Cox proportional hazards analysis, age, comorbid diseases, initial serum albumin concentration, and initial D4/P4 Cr were found to be independent risk factors for mortality. However, in the patients without comorbid diseases, patient survival was not different between group H and the other transport groups combined (p > 0.05), and only age was found to be an independent risk factor for mortality. These data suggest that a high peritoneal transport rate at initial PET is associated with high mortality, and that this is in part due to an increased prevalence of comorbid disease in H transporters. These H transporters with comorbid diseases represent a subset of patients with an especially poor prognosis. In patients without comorbid diseases, high transport status or low serum albumin concentration was not an independent risk factor for mortality.

Macromolecular crowding perturbs protein refolding kinetics: implications for folding inside the cell.

We have studied the effects of macromolecular crowding on protein folding kinetics by studying the oxidative refolding of hen lysozyme in the absence and presence of high concentrations of bovine serum albumin and Ficoll 70. The heterogeneity characteristic of the lysozyme refolding process is preserved under crowded conditions. This, together with the observation that the refolding intermediates that accumulate to significant levels are very similar in the absence and presence of Ficoll, suggests that crowding does not alter substantially the energetics of the protein folding reaction. However, the presence of high concentrations of macromolecules results in the acceleration of the fast track of the refolding process whereas the slow track is substantially retarded. The results can be explained by preferential excluded volume stabilization of compact states relative to more unfolded states, and suggest that, relative to dilute solutions, the rates of many protein folding processes are likely to be altered under conditions that more closely resemble the intracellular environment.

Serum albumin and colorectal cancer risk

To study the relationship between serum albumin and colorectal cancer occurrence. A case-control study nested within a cohort followed from 1968 to 1991. The albumin concentration was determined from serum samples stored at -20 degrees C at baseline in 177 incident colorectal cancer cases and 288 controls matched for sex, age and study region. An elevated risk was present of cancer of the left, distal colon at high serum albumin concentrations. No significant association was observed for the right, proximal colon or the rectum. The relative risks of cancer of the distal and proximal colon among individuals in the highest and lowest quartiles of serum albumin were 17.03 (95% confidence interval 1.48-195) and 0.77 (95% confidence interval 0. 19-3.13), respectively. The present study lends support to the hypothesis that some dietary factor associated with serum albumin may be a risk factor for distal colon cancer.

The increase in CO2 production induced by NaHCO3 depends on blood albumin and hemoglobin concentrations.

To evaluate the origin of H+ ions participating in the generation of CO2 coming from sodium bicarbonate infusion during metabolic acidosis. We hypothesized that these H+ ions come from a back-titration of the main non-bicarbonate buffers present in the blood, i. e. the hemoglobin and the albumin, and thus postulated that the rate of CO2 release from a bicarbonate load is dependent on the concentration of these buffers. Prospective clinical and experimental study. Surgical intensive care unit of a university hospital. (1) Sixteen stable sedated and artificially ventilated critically ill patients with a mild base deficit. (2) Acidotic human blood (bicarbonate 5 mM, pH 7.0) of hematocrit 5, 10, 20 and 40% regenerated from a mixture of frozen fresh plasma and packed red blood cells. infusion of 1.5 mmol/kg sodium bicarbonate over 5 min. Regenerated blood: 25 mM sodium bicarbonate load. continuous measurement of CO2 production (VCO2) on the expired gas using a metabolic monitor and arterial blood gas analysis before (T0), at the end (T5) and at 10, 30 and 60 min after the beginning of the bicarbonate infusion. The increase in VCO2 was 18 +/- 7% leading to a rise in PaCO2 from 39.6 +/- 2.3 at T0 to 46.2 +/- 2.7 mmHg at T5. The increases in VCO2 and in PaCO2 were significantly correlated to the albumin (r = 0.73, p < 0.005 and r = 0.70, p < 0.005, respectively) and to the hemoglobin (r = 0.51, p < 0.05 and r = 0.65, p < 0.01, respectively) concentrations. Regenerated blood: gas analysis 1 min after the bicarbonate load. The increase in PCO2 was closely related to the hematocrit (Ht) of the blood as it was 15.9 +/- 7.5 mmHg for Ht 5%, 29.0 +/- 9.6 for Ht 10%, 44.2 +/- 5.9 for Ht 20% and 71.0 +/- 3.5 for Ht 40% (n = 5 for each, p < 0.001). The importance of the release of CO2 from a bicarbonate load is dependent on the concentration of the blood non-bicarbonate buffers. It is therefore likely that the adverse effects of bicarbonate therapy linked to the CO2 generation are more important in patients with high blood albumin and hemoglobin concentrations.

Human Interphotoreceptor Matrix Contains Serum Albumin and Retinol-binding Protein

It is usually assumed that IRBP (interphotoreceptor retinoid-binding protein) is the only protein present in the interphotoreceptor matrix (IPM) capable of shuttling visual-cycle retinoids between photoreceptors and the retinal pigment epithelium. However, this laboratory previously presented qualitative evidence (Western blots) that serum albumin is present in human IPM. Furthermore, Ong and coworkers (1994) found that cultured RPE cells synthesize serum retinol-binding protein (RBP) and secrete it, mainly into the apical culture medium, which would correspond to the IPM in intact eyes. As both of these proteins can bind all- trans -retinol and 11- cis -retinal, it was of interest to quantify the amounts of albumin and RBP in human IPM. We used radial immunodiffusion to accomplish this. The average molar ratio of serum albumin to IRBP in these samples was 1.9; that of RBP to IRBP was 0.015. The presence of a high concentration of serum albumin in the IPM in situ was confirmed by the intense immunohistochemical staining seen in sections of fresh human eyes. The human case is not unique; various concentrations of albumin were found in the IPM of all vertebrate species examined (by gel electrophoresis). These results indicate that both serum albumin, because of its very high concentration in the IPM, and RBP, because of its comparatively tight binding to retinoids, need to be considered, along with IRBP, as proteins that may participate in visual-cycle transport. The accompanying paper addresses this concern.

Hypernatremia in neonatal elk calves: 30 cases (1988-1998).

To characterize hypernatremia in neonatal elk calves, including clinical signs, incidence, physical examination findings, and possible causes. Retrospective case series. 26 neonatal elk calves were examined; 4 calves were evaluated twice, for a total of 30 examinations. Medical records were reviewed for signalment, history, physical examination findings, results of diagnostic tests, and response to treatment. Hypernatremia was defined as serum sodium concentration > 153 mEq/L. Hypernatremia was diagnosed in 14 calves and was significantly associated with diarrhea, high WBC count, high anion gap, and high serum concentrations of albumin, chloride, creatinine, and urea. Hypernatremia was not significantly associated with survival, but high serum albumin concentration and rectal temperature were significantly associated with survival of calves. Animals given antibiotics and electrolyte solutions orally prior to evaluation were significantly more likely to die than those untreated. Dehydration was a common reason for evaluation but was not significantly associated with survival. Hypernatremia was significantly associated with diarrhea. Treatment of diarrheic elk calves is often the same as that used in bovine calves with diarrhea; however, bovine calves are commonly hypo- or normonatremic. Our experience suggests that treatment protocols used in bovine calves are unsatisfactory for elk calves. The rate at which serum sodium concentration is reduced should be < 1.7 mEq Na/L/h to avoid development of neurologic signs associated with iatrogenically induced cerebral edema.

Retardation Effect of Tyloxapol on Inactivation of Dipalmitoyl Phosphatidylcholine Surface Activity by Albumin

This study investigated the retardation effect of tyloxapol on the inactivation of dipalmitoyl phosphatidylcholine (DPPC) surface activity by albumin. Equilibrium and dynamic surface tensions for mixed DPPC/albumin/tyloxapol systems were measured by using a pulsating bubble surfactometer. The inhibitory effect of albumin on DPPC surface activity was sensitive to albumin concentration. By adding 1 ppm albumin to a 1000 ppm DPPC dispersion, the surface activity of DPPC was almost unaffected. However, at higher albumin concentrations, such as 10 or 100 ppm, the DPPC inactivation was greatly enhanced, resulting in much higher equilibrium and dynamic surface tensions. The amount of tyloxapol required for the reversal of albumin inhibition was examined by adding various amounts of tyloxapol to DPPC/albumin mixtures. The inhibition ability of albumin was not affected if lower concentrations of tyloxapol were present in the subphase. However, the albumin inhibition of DPPC surface activity seems to be greatly diminished by increasing tyloxapol concentration to a level greater than 10 ppm, even the albumin concentration was as high as 100 ppm. For the first time, the extent to which tyloxapol may protect DPPC from inactivation by albumin was directly established. The results suggest that the deleterious effect of albumin on the surface tension-lowering ability of DPPC might be reduced or overcome if appropriate amounts of tyloxapol are present.

Diagnosis of larval cyathostominosis in horses in Belgium.

Between October 1996 and May 1997, 94 horses which were suspected of being infected with strongyles were examined clinically, and samples of faeces were examined for strongyle eggs and cyathostome larvae (L4) and adults. Blood samples were monitored for total protein, albumin and beta-globulins. In 28 of the horses (30 per cent) cyathostome L4 and adults were detected in the faeces, and were significantly associated with the horses' condition, the occurrence of diarrhoea, with lower concentrations of total protein and albumin, and with higher percentages of beta-globulin. Thirty-four of the horses (36 per cent) were excreting strongyle eggs, but in these animals the associations were with high concentrations of total protein and albumin, and lower percentages of beta-globulin. The results showed that during the winter, a horse in poor condition which has diarrhoea, an albumin concentration less than 20 g/litre, and a ratio of albumin:globulin less than 0.7 is very likely to be infected with L4 and adult stages of cyathostomes.

Characteristics of copper corrosion in simulated uterine fluid in the presence of protein.

In order to acquire more knowledge of the performance of copper-bearing intrauterine devices (Cu-IUDs), corrosion behavior of copper in a simulated uterine fluid was investigated in the presence of proteins. The proteins studied included serum albumin, gamma-globulin and hemoglobin. Electrochemical polarization resistance measurements indicated that, in all cases under study, the corrosion rate of copper declined with time and the proteins always increased the rate. Moreover, different kinds of protein showed different dependence of copper corrosion rate on protein level. Addition of serum albumin initially raised the copper corrosion rate; however, the higher albumin concentration resulted in less promotion of the corrosion. X-ray diffraction (XRD) of the specimen surface showed that, both in the presence and absence of serum albumin, cuprous oxide was the only corrosion product, even though at higher concentrations of albumin less cuprous oxide was formed. This implies that serum albumin does not alter the corrosion mechanism. Electrochemical cathodic reduction of the oxide film and chemical analysis of solution after corrosion testing proved that the proportion of soluble ionic copper in the whole corrosion products varied with the albumin level. The copper corrosion rate in the presence of gamma-globulin or hemoglobin increased monotonically with increasing concentration of the protein. These three proteins shifted the corrosion potential of copper towards negative. It could be inferred that the proteins accelerated the anodic dissolution process of copper and hence enhanced its corrosion.

Blood–cerebrospinal fluid barrier impairment as indicator for an immune process in schizophrenia

An impairment of the blood–cerebrospinal fluid barrier (BCB) has repeatedly been described in schizophrenic patients. A BCB impairment can be due to vascular leakage during an inflammatory process, or to neuroleptic treatment. The soluble intercellular adhesion molecule-1 (sICAM-1) has been demonstrated to be a reliable marker for an inflammatory process causing an BCB impairment. To clarify the basis of a BCB impairment in schizophrenic patients, we measured the sICAM-1 levels in CSF of 40 schizophrenic patients. High concentrations of sICAM-1 were found to be related to high concentrations of albumin, IgG and total protein in CSF. A BCB impairment was associated with high levels of sICAM-1. Our data indicate an inflammatory mechanism of BCB impairment in schizophrenics and should enrich the discussion on an expanded immunological diagnosis in schizophrenia.

Dose-dependent agonist and antagonist effects of the platelet-activating factor analogue 1-palmitoyl-2-acetoyl- sn-glycero-3-phosphocholine on B lymphocytes

Background: Platelet activating-factor (PAF), an ether-linked phospholipid, is a potent activator of B lymphocyte cell lines. The related ester-linked phospholipid, 1-palmitoyl-2-acetoyl- sn-glycero-3-phosphocholine (PAGPC), is synthesized by tissues important in B-cell development. Objectives: We examined whether PAGPC was capable of influencing immunoglobulin synthesis in B lymphocytes and compared its action with that of PAF. We also examined the interaction of the two mediators as agonists or competitive antagonists. Methods: Ramos, an IgM-secreting immature B-cell line that expresses PAF receptor, was used in these experiments. The effect of PAF, PAGPC, or both mediators together on IgM secretion and anti-IgM–mediated apoptosis was measured. Results: Both PAF and PAGPC stimulated IgM production in Ramos cells in a dose-dependent fashion, with PAGPC being approximately three logs less potent than PAF. The effect of both mediators was inhibited by specific PAF receptor antagonists. Preincubation with suboptimal concentrations of PAGPC inhibited the ability of PAF to increase IgM secretion by Ramos cells. Additionally, preincubation with low concentrations of PAGPC prevented PAF from rescuing Ramos cells from apoptosis induced by cross-linking the B-cell receptor with anti-IgM antibodies. PAGPC caused PAF receptor desensitization because displacement of bound PAGPC with high concentrations of bovine serum albumin did not reverse its PAF antagonist effect. Conclusions: PAF and PAGPC are biologically active phospholipids, but PAF is approximately 1000 times more potent. At high concentrations, PAGPC acts similarly to PAF, whereas at lower concentrations, PAGPC acts as a functional PAF antagonist. Because it is secreted at sites of inflammation and allergic reactions, PAGPC may be an endogenous regulator of the effects of PAF. (J Allergy Clin Immunol 1998;102:231-7.)