Brain tissues

Synthesis. In contrast to pituitary hormones, which usually can be obtained in pure form only after extraction from animal tissues, brain oligopeptides are readily available because of their small size. The synthetic repHca represents the most economical and readily accessible source for the oligopeptides. Two techniques are available for laboratory synthesis of oligopeptides, ie, solution chemistry and soHd-phase peptide synthesis (SPPS). 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

Drugan, RC, Basile, AS, Crawley, JN, Paul, SM and Skolnick, P (1987) Peripheral benzodiazepine binding sites in the Maudsley Reactive rat selective decrease confined to peripheral tissues. Brain Res. Bull. 18 143-145. 

Tissues (brain, heart, lung, kidney, liver, and testes) Dry ashing of sample dissolution in HN03 AAS No data No data Exon et al. 1979... 

Guan, X. M., Yu, H., Palyha, O. C. et al. (1997). Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res. Mol. Brain Res. 48, 23-9. 

A single enzyme, inositol monophosphatase, leads to loss of the remaining phosphate and the regeneration of free inositol. This enzyme exhibits similar affinities for all five of the equatorial inositol monophosphate hydroxyls. Inositol 2-phosphate, which is not produced in this degra-dative pathway, is a poor substrate, a property that is probably attributable to its axial configuration. The enzyme is inhibited by Li+ in an uncompetitive manner i.e. the degree of inhibition is a function of substrate concentration. The putative link between the ability of Li+ to interfere with phosphoinositide turnover and its therapeutic efficacy in the treatment of bipolar disorders is discussed in Box 20-1 and Chapter 55. It should be noted that unlike most other tissues, brain can synthesize inositol de novo by the action of inositol monophosphate synthase, which cyclizes glucose 6-phosphate to form I(3)P. The enzyme has been localized immunohistochemically to the brain vasculature. 

GLUTl Most tissues (brain, red ceUs) 1 mM Basal uptake of glucose... 

Due to its lipophilic character, chloroform accumulates to a greater extent in tissues of high lipid content. As shown by the results presented above, the relative concentrations of chloroform in various tissues decreased as follows adipose tissue > brain > liver > kidney > blood. 

In the late 1960s, two groups reported results that indicated the possibility of more than one form of MAO. In 1967, Maitre suggested that tissue (brain vs liver)-dependent potencies of inhibitors could be explained by the presence of different forms of MAO [4]. In 1968, Johnston published an analysis of unusual kinetics observed with the new MAO inhibitors that were being developed. He concluded that the most reasonable hypothesis to explain such results as double sigmoid curves was the existence of at least two forms of the enzyme [5]. By the mid-1980s, differences of substrate and inhibitor specificity of two MAOs, now called MAO A and B, were well understood [6]. 

The acute effects of a single dose of most psychotropics are terminated by redistribution. An example would be the acute sedative effects of intravenously administered lorazepam, which rapidly enters the brain from the blood. A disproportionate amount of the dose enters the CNS because of its greater vascularity in comparison with peripheral adipose tissue. Brain concentration subsequently falls as the drug redistributes out of the brain into the plasma and then into other peripheral compartments. This fall in brain concentration terminates acute psychoactive effects of a single dose of a drug such as lorazepam. 

No deaths occurred during the study. Treatment-related reductions in body weight gain of 34 and 33%, respectively, were noted in the 5.6 mg/kg females and 10.9 mg/kg males, respectively. Clinical signs included emesis and diarrhea, but were not dose related. No pathology of any nervous system tissue (brain, spinal cord, sciatic nerve) was noted under either gross or microscopic examination. 

An important characteristic of the brain that largely determines its susceptibility to toxicants is the blood-brain barrier, which restricts transfer of substances between the blood and brain tissue. Brain cells have very tight junctions between each other, such that toxicants and their metaboliltes must move across cell membranes either by active transport processes or by virtue of their lipo-philicity. 

The sample preparation procedures for the direct analysis of small molecules in tissue have been described by several papers [120-124], Tissues (brain, heart, lung, kidney, liver, etc.), were immediately frozen and stored at -80 °C after harvest. The frozen tissues were subsequently cut into serial 10-20 pm thick section which was typically prepared by cryosectioning on a microtome at a temperature of -20 °C. The adjacent sections were gently mounted onto a conductive surface, MALDI imaging target plate or glass slides. These plates were desiccated under low vacuum for a short period of time until dry, then robotically or manually coated with the... 

CRABP-GST is immobilized onto a glutathione-containing resin at a concentration that saturates the resin. A complex lipid mixture was prepared by combining a concentrated lipid extract derived from mouse tissue (brain) [5] (DMSO stock) with exogenously added retinoic acid (RA, positive control) and 13C-oleic acid (negative control). Analysis of this complex lipid mixture by LC-MS prior to incubation with immobilized CRABP demonstrated that the mixture contained RA (added), phospholipids, acylglycerols, cholesterol esters, and cholesterol. A portion of this mixture (corresponding to 1 nmol of RA) was added to PBS (DMSO concentration should not exceed 5%) and incubated with the CRABP-GST bound beads for 1 h. 

GLUT Transporters Compare the localization of GLUT4 with that of GLUT2 and GLUT3, and explain why these localizations are important in the response of muscle, adipose tissue, brain, and liver to insulin. 

It is currently not clear as to how many PTX substrates there are and, of these, how many may co-exist in any given tissue. Brain has been reported as containing three PTX substrates of Mr 39000, 40000 and 41000 [73]. In heart and fat two PTX substrates were reported [163-165], Human erythrocytes appear to have one PTX substrate of A/r 40000 [29] which can be fractionated into two [151]. Prolonged exposures of autoradiograms of human erythrocyte, bovine brain, human neutrophil and rat liver PTX substrates reveal still a third substrate of apparent Mt = 43 000 [166,167]. As illustrated in Fig. 7, even more, up to five distinct proteins, can be visualized if membrane proteins are fractionated by SDS-PAGE in the presence of an urea gradient [151]. The functional difference between these PTX-labeled bands is not known at present. 

Histopathological evaluation of tissues (brain, spinal cord, peripheral nervous system)... 

The rapid diffusibUity of NO has critically important imphcations for its chemistry in the biological setting. The speed with which NO moves by random diffusion can be illustrated by consideration of its root mean square distance of displacement, which describes the distance a single NO molecule will move in any time interval based on its diffusion constant D (which is similar for aqueous solution and also tissue (brain) ) ... 

Mustard preferentially accumulates in fatty tissue (in deereasing concentration fat, skin with subcutaneous tissue, brain, kidney, muscle, liver, cerebrospinal fluid, spleen, and lung) (Somani and Babu, 1989). Excretion is through the urine in rabbits, mice, and rats (lARC, 1975). Mustard is exereted over 72 to 96 h after IV administration in rats and miee (Dacre and Goldman, 1996 Maisonneuve et al, 1993). Complete blood count (CBC) changes are not evident for 3 to 5 days post-exposure. Leukopenia usually oeeurs at day 7 to 10 (Garigan, 1996). 

Cashiorr ME, Barrks WA, Bost KL, Kastin AJ (1999) Transmission routes of HIV-1 gpl20 horn brain to lymphoid tissues. Brain Res 822 26-33. 

Corti S, Locatelh F, Donadoni C, Guglieri M, Papadimitriou D, Strazzer S, Del Bo R, Comi GP (2004) Wild-type bone marrow cells amehorate the phenotype of SOD1-G93A ALS mice and contribute to CNS, heart and skeletal muscle tissues. Brain 127 2518-2532. 

Perala M, Hirvonen H, Kalimo H, et al. Differential expression of two ( -adrenergic receptor subtype mRNAs in human tissues. Brain Res Mol Brain Res 1992 16 57-63. 

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