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Biomedical subjects

D J Reed

Publications and source records attributed to D J Reed.

At least 145 records · Page 8Linked to original sources

Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus.

1. The regulation of cerebrospinal fluid (c.s.f.) bicarbonate concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Decreases in plasma bicarbonate concentration caused relatively small changes in the c.s.f. bicarbonate concentration. 3. Alterations in c.s.f. bicarbonate concentration (c.s.f. HCO3-=9 or 28 m-equiv/l.) were countered by changes in the bicarbonate concentration of the fluid produced by the plexus or in the rate of bicarbonate transport which returned c.s.f. bicarbonate towards normal. 4. There was significant regulation of pH in the choroid plexus fluid during hypocapnia and hypercapnia. 5. Alterations of plasma acid-base status did not significantly alter the potential difference across the choroid plexus. However, the potential difference increased when c.s.f. bicarbonate was increased and decreased when c.s.f. bicarbonate was decreased. 6. The data indicate that the bicarbonate concentration in the c.s.f. is actively regulated by the choroid plexus during acid-base disturbances occurring either systemically or in the c.s.f.

Animals↗

Developmental studies of the compartmentalization of water and electrolytes in the choroid plexus of the neonatal rat brain.

Rats of various postnatal ages were utilized to study developmental changes in the distribution of Na, K and H2O between the various compartments of the lateral ventricular plexus (LVP). During the 3 weeks after birth, as the LVP grows from 0.5 to 0.8 mg, there is a significant increase in plexus K which is accompanied by a progressive decrease in Na and H2O. Also, during this postnatal period the decrease in [3h]inulin space in the plexus is proportional to the decrease in the Na space. Between 3 weeks and adulthood, the [3h]inulin and Na spaces are both augmented to a similar extent; moreover, during this same period of development there is a trebling of the residual [51cr]erythrocyte volume. Despite the substantial changes in the volume of the extracellular fluid and of the residual blood in the plexus with age, the calculated concentrations (mEquiv./kg H2O) of choroid cell Na (30-35) and K (145-155) are similar for all ages investigated. The derived data for cellular ionic concentration, together with the analysis of the ionic concentration gradients (cerebrospinal fluid/plasma H2O), suggest that the transport mechanism which translocates Na and K across the choroidal membrane is operative as early as 3-4 days postnatal. The important role of the choroid plexus in central nervous system homeostasis is discussed in relation to the developing brain.

Age Factors↗

Regulation of cerebrospinal fluid potassium by the cat choroid plexus.

1. The regulation of cerebrospinal fluid (c.s.f.) potassium concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Hyperkalaemia (plasma potassium concentration greater than 6 m-equiv/l.) caused relatively small increases in c.s.f. potassium concentration. 3. Alterations in c.s.f. potassium concentration (c.s.f. K = 0-15 or 6-56 m-equiv/l.) were countered by changes in potassium concentration of the produced fluid or in the rate of potassium transport which returned c.s.f. potassium towards normal. 4. The data indicate that potassium concentration in c.s.f. secreted by the choroid plexus is actively regulated by the plexus whether the primary alteration in potassium occurs in plasma or c.s.f.

Animals↗

Microsomal monooxygenation of the carcinostatic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Synthesis and identification of cis and trans monohydroxylated products.

Liver microsomal hydroxylation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was shown to occur on the cyclohexyl ring at positions 3 and 4. Four metabolites were isolated by selective solvent extraction and purifed by high-pressure liquid chromatography. cis-4-, trans-4-, cis-3-, and trans-3-OH derivatives of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea were synthesized and their chromatographic, mass spectral, and nuclear magnetic resonance characteristics matched those of the metabolites. The position of ring hydroxylation and the identity of each geometric isomer were established by nuclear magnetic resonance using a shift reagent in conjunction with spin decoupling techniques. Microsomes from rats pretreated with phenobarbital showed a sixfold increase in hydroxylation rate (19.5 vs. 3.3 nmol per mg per min). The induction was quite selective for cis-4 hydroxylation (19-fold); however, induction of trans-4 (threefold), cis-3 (threefold), and trans-3 (twofold) hydroxylation did occur. Quantitatively the cis-4-hydroxy metabolite was 67of the total product by phenobarbital-induced microsomes and 21% for normal microsomes. Microsomes from animals pretreated wit- 3-methyl-cholanthrene gave about the same rate and product distribution that normal microsomes gave. A mixture of 80% carbon monoxide-20% oxygen inhibited formation of all four hydroxy metabolites with the inhibition ranging from 55 to 78%.

Animals↗

2-chloroethanol formation as evidence for a 2-chloroethyl alkylating intermediate during chemical degradation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea.

Chemical degradation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea or 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea in buffer under physiological conditions resulted in the formation of a significant quantity of 2-chlorethanol (18 to 25% of the initial nitrosourea concentration). Other degradation products observed included acetaldehyde (5 to 10%), vinyl chloride (1 to 2%), ethylene (1 to 2%), and cyclohexylamine (32%), but not 1,3-dicyclohexylurea. The 2-chlorethyl moiety of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was trapped with halide ions, CI-, BR-, and I-, to form the corresponding dihaloethanes which were identified by gas chromatography-mass spectrometry techniques. High-pressure liquid chromatographic procedures were developed for the separation and quantiation of the nitrosoureas and many of their degradation products. It is postulated that a new mode of 1(2-chloreoethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea degradation can occur that is not the loss of the chloro group as chloride ion, but the loss of the N-3 hydrogen as a proton. Then the corresponding isocyanate and 2-chloroethyidiazene hydroxide are formed, with the latter intermidiate becoming an alkylating species, possibly in part as a 2-chloroethyl carbonium ion.

Acetaldehyde↗

Active transport of sodium and potassium by the choroid plexus of the rat.

1. Choroid plexus from the lateral ventricle in the adult rat was found to contain approximately 54 m-equiv Na(+) and 89 m-equiv K(+) per kg wet tissue.2. The total water (79%), the extracellular space (21%) and the red blood cell volume (8-9%) in choroid plexus were quantified separately by analysing the distribution of [(14)C]antipyrine, [(14)C]inulin and (51)Cr-tagged erythrocytes, respectively, between this tissue and plasma water.3. The tissue electrolyte data together with the compartmental (space) data were used to calculate an average concentration of Na(+) (39 m-equiv/kg cell H(2)O) and of K(+) (144) in the choroid cell.4. Under various experimental conditions known to stimulate or inhibit the Na(+)-K(+) transport system in other tissues, there were significant changes (10-40 m-equiv/kg cell H(2)O) in the concentrations of both these cations in the plexus epithelial cells.5. Choroid cell K(+) was not independent of the concentration of K(+) in plasma since substantial fluctuations in cell K(+) occurred in rats rendered either hypo- or hyperkalaemic; also, the choroid cell apparently cannot maintain a constant gradient between itself and c.s.f. in the face of kalaemic disturbances.6. Evidence is offered to support the hypothesis that the choroid plexus of the lateral ventricle has a Na(+)-K(+) pump, the operation of which contributes to the maintenance of K(+) homoeostasis in the C.N.S.

Animals↗