Brain fluids cerebrospinal fluid

Specific barriers may serve to limit dmg distribution. The placental barrier is of obvious importance to dmg action in the fetus. Dmg transfers across the placenta primarily by Hpid solubiHty. Hence, this barrier is not particularly restrictive. Similarly, the Hpid solubiHty of a dmg is a primary deterrninant in access to the brain and cerebrospinal fluid. Generally, hydrophilic or charged dmgs can also penetrate to these latter areas, but the result is slow and incomplete. The blood brain barrier is composed of cells having tight junctions which are much less permeable to solutes than are the endotheHal cells of other tissues. 

Glycosydation AChE and BChE carry 3 and 9, respectively, N-glycosylation consensus sequences attaching carbohydrate residues to the core protein via asparagines. Different molecular forms of the enzymes in various tissues, show different number and composition of carbohydrate residues. N-glycosylation at all sites was shown to be important for effective biosynthesis, secretion and clearance of ChEs from the circulation. Altered patterns of AChE glycosylation have been observed in the brain and cerebrospinal fluid of Alzheimer s disease (AD) patients, with potential diagnostic value. 

Ballantyne, B. 1975. Blood, brain and cerebrospinal fluid cyanide concentrations in experimental acute cyanide poisoning. Jour. Forensic Sci. Soc. 15 51-56. 

Blood from normal subjects contains 14-60 m ig/ml, serum 25-75 mpg/ml, urine 100-200 m[ig of B8/ml of fluid cerebrospinal fluid contains less than 1 m ig/ml. Normal human liver, obtained by biopsy, contains between 10-20 mpg of B6/mg of dried tissue rat brain between 3.5-5 m(ig/mg. (cf. Table 9). 

Table V contains data for two model substances, p-aminohippurate (PAH) and phenol red. Consideration of the highest values in this table tells you where the major portions of the substances appear. For example, urine and bile show the largest concentrations of PAH and phenol red. Both compounds appear in significant concentrations in the kidney while the values in muscle, brain and cerebrospinal fluid (CSF) are invariably lower than the values seen in plasma. The values in parentheses (Table V) are percent of the administered dose in a given tissue or fluid compartment. They add to the previous information by revealing the overall importance of a particular compartment in the disposition of a substance. For example, while the hepatic concentrations of PAH and phenol red at 4 hrs. are only about 2-fold those of plasma, the large size of the shark liver relative to its body weight, typically about 10%, leads to the appearance of 30-40% of these substances in the liver. The relative handling of these compounds by the urinary and biliary system is obvious from considering the percentage figures. Thus in 24 hours phenol red is about equally distributed in the bile and urine (38 vs 31%) the urinary route is the dominant route of excretion of PAH, i.e., 56 vs 2%.

Numerous studies have been published on the in vivo metabolism of peptides. However, these studies are concerned mainly with assessment of pharmacokinetic parameters such as half-life and clearance. Only seldom is the in vivo biotransformation of peptides that contain only common amino acids investigated in any detail, due to the difficulty of monitoring products of proteolysis that are identical to endogenous peptides and amino acids. More importantly, such studies fail to yield mechanistic and biochemical insights. For this reason, we begin here with a discussion of the metabolism of just a few peptides in some selected tissues, namely portals of entry (mouth, gastro-intestinal tract, nose, and skin), plasma, organs of elimination (liver, kidney), and pharmacodynamic sites (brain and cerebrospinal fluid). These examples serve as introduction for the presentation in Sect. 6.4.2 of the involvement of individual peptidases in peptide metabolism. 

Moncrieff J. (1989). Determination of pharmacological levels of harmane, harmine, and harmaline in mammalian brain tissue, cerebrospinal fluid, and plasma by high-performance liquid chromatography with fluorimetric detection. J Chromatogr. 496(2) 269-78. 

The nitrosoureas are alkylating agents that are highly lipid soluble and share similar pharmacological and clinical properties. Carmustine (BCNU), lomustine (CCNU), and semustine (methyl-CCNU) are chemically unstable, forming highly reactive decomposition products. The chemical half-life of these drugs in plasma is only 5 to 15 minutes. Their marked lipid solubility facilitates distribution into the brain and cerebrospinal fluid (CSF). 

Heyes M. P., Swartz K. J., Markey S. P., and Beal M. F. (1991). Regional brain and cerebrospinal fluid quinolinic acid concentrations in Huntington s disease. Neurosci. Lett. 122 265-269. 

Active against cancers of the brain and cerebrospinal fluid. 

The result of this anatomical characteristic of endothelial cells in the CNS is an increased resistance to water-soluble and ionized drugs entering the brain, and cerebrospinal fluid (CSF), from capillary blood. However, in a few areas of the brain the barrier is absent. These areas include the lateral nuclei of the hypothalamus, the area postrema of the fourth ventricle, the pineal body, and the posterior lobe of the hypophysis. Highly lipophilic compounds can cross the barrier. Tranquilizers such as diazepam and its analogs are known to gain access rapidly to the CSF with a half-life (tm) entry time of less than 1 minute. 

The blood-brain barrier can be overcome in certain circumstances. For example, in rats, uptake of mouse anti-Cryptococcus neoformans monoclonal antibodies into brain or cerebrospinal fluid is very limited after intravenous administration, but good uptake occurs after intrathecal administration... 

Glutathione synthesis is impaired in patients at the level of the GCL enzyme, as measured in fibroblasts. In addition, genetic analysis showed an association between schizophrenia and the two GCL subunits. These findings are consistent with low brain and cerebrospinal fluid (CSF) glutathione levels. 

Wong SL, Van Belle K, Sawchuk RJ (1993) Distributional transport kinetics of zidovudine between plasma and brain extracellular fluid/cerebrospinal fluid in the rabbit— Investigation of the inhibitory effect of probenecid utilizing microdialysis. J Pharmacol Exp Ther 264 899-909. 

Most proteomics analyses involve 2-D electrophoresis and MALDl-TOF MS steps, as this approach allows for a reliable quantification of changes in protein levels. In one study, the LC-MS/MS approach was used for the detection of proteins enriched in amyloid plaques in the AD brain (liao et al., 2004). Employing the former proteomic approach, levels of about 100 proteins were foimd to be changed in the AD brain and cerebrospinal fluid (CSF) in comparison with the control brain and CSF, respectively (Table 15.1). These proteins have various functions, mainly involved in neurotransmission, guidance, signal transduction, metabolism, detoxification, and conformational changes. The CSF proteins are plasma proteins. 

Brain and cerebrospinal fluid (CSF). The capillaries of the cerebral circulation differ from those in most other parts of the body in that they lack the filtration channels between endothelial cells through which substances in the blood nominally gain access to the extracellular fluid. Tight junctions between adjacent capillary endothelial cells, together with their... 

Dziegielewska KM, Hinds LA, Mollgard K, Reynolds ML, Saunders NR (1988) Blood-brain, blood-cerebrospinal fluid and cerebrospinal fluid-brain barriers in a marsupial (MACROPUS EUGENII) during development. J Physiol 403 307-388. 

In most applications, the bioanalysis involves the analysis of a number of dmgs, or one dmg and (some of) its metabolites in biological fluids, especially whole blood, plasma, serum, or urine. However, other matrices are studied as well various tissues (skin, liver, brain, thyroid gland), faeces, hair, tear fluid, cerebrospinal fluid, semen. In most studies, the analysis of samples from human origin or from rats is performed, although the analysis of samples from rabbits, mice, minipigs, dogs, and monkeys is also performed. 

Problems with recovery are avoided when sampling the extracellular brain tissue by means of a push-pull cannula. A push-pull cannula consists of two coaxial assembled hollow needles (cannulae) which are implanted into the brain. Artihdal cerebrospinal fluid is infused through the inner cannula and withdrawn through the outer cannula [5-8],... 

Pharmacokinetic Rapidly, completely absorbed from GI tract. PB 25%-38% metabolized in liver widely distributed crosses blood-brain barrier, cerebrospinal fluid primarily excreted in urine minimal removal by hemodialysis. 

Gordon, L. B., Knopf, P. M., and Cserr, H. F., Ovalbumin is more immunogenic when introduced into brain or cerebrospinal fluid than into extracerebral sites, J. Neumimmunol., 40, 81, 1992. 

Torsteinsdottir, S., Geoigsson, G., Gisladottir, E., Rafnar, B., Palsson, P. A., and Petursson, G., Pathogenesis of central nervous system lesions in visna cell-mediated immunity and lymphocyte subsets in blood, brain, and cerebrospinal fluid, Ann. N.Y. Acad. Sci., 724, 159, 1994. 

Inao, S., Marmarou, A., Clarke, G.D., Andersen, B.J., Fatouros, P.P., and Young, H.F. (1988) Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury. Journal of Neurosurgery, 69, 736-744. 

Rarribeck, B. et al. (2006) Comparison of brain extracellular fluid, brain tissue, cerebrospinal fluid, and serum concentrations of antiepileptic drugs measured intraoperatively in patients with intractable epilepsy. Epilepsia, 47 (4), 681-694. 

A / iV-imidazoleacetic acid (I A A, 99), a metabolite of histidine 100, and histamine S found in brain and cerebrospinal fluid , has been synthesized by oxidizing A, Af-DL-histidine with sodium hypochlorite, subsequent acid hydrolysis of the formed A, A -imidazoleacetonitrile 101 and separation of the product 99 on an anion exchange column with 0.1 N acetic acid (equation 42). The A, A -IAA obtained served as an internal standard for GC-MS analysis of physiological fluids. 

Best, J. D. et al., In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-l,l,l-trifluoromethanesulfonamide (MRK-560) in the rat, J. Pharmacol. Exp. Ther., 317(2), 786, 2006. 

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