Cerebrospinal fluid albumin

APPLICATIONS IN BIOLOGICAL AND CLINICAL CHEMISTRY 519 TABLE XI Correlation Between Results of Polarographic Examination and Absolute Denaturation Capability of Cerebrospinal Fluid Albumin ... 

In general we can say that polarographic examination of the cerebrospinal fluid is about equally important as the determination of the absolute denaturation capability of cerebrospinal fluid albumin, the correlation coefficient being r = -1-0.714 (98). 

The simplest method is the calculation using the Delpech-Lichtblau quotient, which is based on parallel determinations of concentrations of IgG and albumin in cerebrospinal fluid and serum. The mathematical structure of the formula is as follows ... 

Although the examination of total protein in cerebrospinal fluid is quite valuable, it is necessary to mention that this parameter does not provide exact information on the function of the blood-CSF barrier. This is easy to understand. The increased concentration of total protein in cerebrospinal fluid can be based both on the failure of the barrier with a subsequent increase in the concentration of albumin and of other proteins originating from serum and on a more significant intrathecal synthesis of immunoglobulins, especially in levels of IgG. 

The albumin quotient is the most precise, routinely used criterion for assessment of the function of the blood-CSF barrier because albumin in cerebrospinal fluid originates exclusively from serum. Its parallel determination during the monitoring of any CSF protein is necessary because this is the only way to differentiate its increased concentration in cerebrospinal fluid due to passive penetration of the respective serum protein from a more specific increase in the concentration of the monitored protein. It is based on its intrathecal synthesis or on a specific transport mechanism for the given protein across the blood-CSF barrier. Unfortunately, some clinicians disregard this recommendation, and this elementary fact is not sufficiently emphasized in publications on cerebrospinal fluid (A22). 

Quantitative methods are based on the determination of the concentrations of IgG and albumin correspondingly in cerebrospinal fluid and in serum. This way, it is possible to differentiate the increased concentration of IgG in CSF, which is based on the penetration of this protein from serum under the conditions of increased serum concentrations or failure of the blood-CSF barrier (Reiber s formulas see Section 3.2.3). 

During the monitoring of any protein in cerebrospinal fluid, it is necessary to bear in mind the functional status of the blood-CSF barrier, serum concentration of the respective protein, and the dimensions of the molecule (or the information based on the molecular weight). These data principally influence the resulting concentration in cerebrospinal fluid. It must also be emphasized again that the parallel determination of albumin in cerebrospinal fluid and serum is necessary. 

K3. Kamp, H. H., Luderer, T. K. J., Muller, H. J., and Sopjes-Kruk, A., Rapidimmunoturbidimetric assay of albumin and immunoglobuUn G in serum and cerebrospinal fluid with an automatic discrete analyser. Clin. Chirrr Acta 114,195-205 (1981). 

T4. Tourtellotte, W. W., Tavolato, B., Parker, J. A., and Cotniso, P, Cerebrospinal fluid electroimmunodiffusion. An easy, rapid, sensitive, and valid method for the simultaneous determination of immunoglobulin G and albumin. Arch. Neurol. 25, 345-350 (1971). 

Pharmacokinetics Well absorbed from G1 tract. Protein binding 97%. Principally bound to albumin. Distributed into cerebrospinal fluid. Metabolized in the liver. Undergoes extensive first-pass effect. Excreted in urine and feces. Half-life 19-37 hr. 

In our studies the ninhydrin-reaction- revealed a number of new fractions, one of which is fluorescent. There are two fractions with a mobility greater than albumin, and two with a mobility lower than y-globulin (Fig. 62b). Some of these are present in many sera, some are rare. They are present in the ultrafiltrate of serum where also a central fraction can be seen, which has the mobility of the y-globulin. They are also present in normal cerebrospinal fluid and were found in hemoglobin preparations. It is not clear if only amino acids are involved, because larger molecules also react with ninhydrin. 

Distribution Sulfa drugs are distributed throughout body water and penetrate well into cerebrospinal fluid, even in the absence of inflammation. They can also pass the placental barrier and into breast milk. Sulfa drugs are bound to serum albumin in the circulation the extent of binding depends on the particular agent. 

Contrasting milieux. Cerebrospinal fluid has a low content of albumin and other proteins compared with plasma. 

Bilirubin - an apolar, water-insoluble lipophile substance - is potentially toxic. It is bound to serum albumin and transported to the sinusoidal membrane of the liver cell as a bilirubin-albumin complex, (s. fig. 3.1) The binding capacity of albumin is exceeded only at a serum bilirubin concentration of >4—5 mg/dl. In the case of decreased albumin binding (e. g. in acidosis) or oversaturated binding capacity, there is a danger of toxic cell damage due to the diffusion of unbound bilirubin into the cells (in some cases accompanied by kernicterus). Neonates and premature babies are at particular risk because of their immature blood-cerebrospinal fluid barrier. Albumin-bound bilirubin can function as an antioxidant to intercept free radicals and/or O2 radicals. (93) (s. tab. 3.25)... 

Note First results for the determination of glucose in urine and cerebrospinal fluid (CSF) using this hexokinase method have been published (SI99, S224). In this case the samples should be diluted with 1% bovine albumin solution. Good correspondence to a comparative method was described for CSF (S224). A 30% deviation was known for urine samples (SI99). 

Nephelometry, immunoturbidimetry, electroimmunodiffu-sion, and RID are most often used for measurements of albumin and IgG in cerebrospinal fluid. Apparent absence of IgG may be due to its. degradation by proternases in the specimen. RIA is required for determination of specific pro-teins present in very low concentrations (e.g., IgM). The reference interval for albumin levels in lumbar CSF by RID is 17.7 to 25.1 mg/dL. IgA, IgD, and IgM, measured by RIA, are each normally less than 0.2 mg/dL. Reference intervals for IgG are age related their means increase from 3.5 mg/dL in the 15- to 20-year-old group to 5.8 in adults aged 60 or older. The usual reference interval for CSF IgG in adults is 0.8 to 4.2 mg/dL for total protein, 15 to 45 mg/dL. Total protein levels are considerably higher in neonates, and in healthy elderly adults, concentrations up to 60 mg/dL are considered normal. 

Rao NR, Pattabiraman TN. Alphaz-macroglobufin, albumin, and chymotrypsin inhibitory capacity in cerebrospinal fluid as indices of blood-cerebrospinal fluid barrier. Biochem Med Metab Biol 1986 36 317-21. 

Harling-Beig, C. J., Knopf, P. M., Merriam, J., and Cserr, H. F., Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid, J. Neumimmunol., 25, 185, 1989. 

Physiological free copper concentrations are certainly decisive for determining a role for copper in PrP cellular function. It is important to recall the properties of Cu2+ in buffer solution. The solubility product (Ksp) of Cu(OH)2 at physiological pH is in the order of 10 20. i.e., rather small. It is therefore likely that it is bound to other compounds like, e.g., human serum albumin which binds copper in the picomolar range [92]. To evaluate whether PrP is a functional copper binding protein one has to determine the relative concentration of membrane attached PrPc and that of albumin in the cerebrospinal fluid which is about 3 pM [93]. However, the free concentration of copper has not been determined. Inside cells... 

Curran, R.E., et al.. Cerebrospinal fluid production rates determined by simultaneous albumin and inulin perfusion. Experimental Neurology, 1970. 29, 546-553. 

The function of the device containing 2-mm long monolith was first tested on capture of fluorescein isothiocyanate (FITC)-labeled lysozyme from its mixture with cytochrome c. The capture was monitored via an increase in fluorescence of the monolith. The ability of the monolith to selectively capture lysozyme from the mixture was validated by MALDI-TOF mass spectrometry. Since the Cibacron-blue-3G-A ligand has a strong affinity for albumins, the ultimate function was successfully demonstrated with capture of albumin from human cerebrospinal fluid. ... 

Li, C. and Lee, K. H., Affinity depletion of albumin from human cerebrospinal fluid using Cibacron-blue-3G-A-derivatized photopatterned copolymer in a microfluidic device, Anal. Biochem., 333, 381, 2004. 

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