Uptake of 36Cl and 22Na by the Brain-Cerebrospinal Fluid System: Comparison of the Permeability of the Blood-Brain and Blood-Cerebrospinal Fluid Barriers

Abstract: Transport and permeability properties of the blood-brain and blood-CSF barriers were determined by kinetic analysis of radioisotope uptake from the plasma into the CNS of the adult rat. Cerebral cortex and cerebellum uptake curves for ³⁶Cl and ²²Na were resolved into two components. The fast component (t_½ 0.02–0.05 h, fractional volume 0.04–0.08) is comprised of the vascular compartment and a small perivascular space whereas the slow component (t_½ 1.06–1.69 h, fractional volume 0.92–0.96) represents isotope movement across the blood-brain barrier into the brain extracellular and cellular compartments. Uptake curves of both ³⁶Cl and ²²Na into the CSF were also resolved into two components, a fast component (t_½ 0.18 h, fractional volume 0.24) and a slow component (t_½ 1.2 h, fractional volume 0.76). Evidence suggests that the fast component represents isotope movement across the blood-CSF barrier, i.e., the choroid plexuses, whereas the CSF slow component probably reflects isotope penetration primarily from the brain extracellular fluid into the CSF. The extracellular fluid volume of the cerebral cortex and cerebellum was estimated as ?13% from the initial slope of the curve of brain space versus CSF space curve for both ³⁶Cl and ²²Na. Like the choroid plexuses, the glial cell compartment of the brain appears to accumulate Cl from 2 to 6 times that predicted for passive distribution. The relative permeability of the blood-CSF and blood-brain barriers to ³⁶Cl, ²²Na, and [³H]mannitol was determined by calculating permeability surface-area products (PA). Analysis of the PA values for all three isotopes indicates that the effective permeability of the choroidal epithelium (blood/CSF barrier) is significantly greater than that of the capillary endothelium in the cerebral cortex and cerebellum (blood-brain barrier).     

Insulin-induced lipoatrophy: evidence for an immune pathogenesis.

Skin biopsy samples from 14 diabetic patients with lipoatrophy at injection sites and from five insulin-treated diabetic patients without such lipoatrophy (controls) were examined by immunofluorescence for the deposition of immunological components. Also sera from 13 of the patients with lipoatrophy and from all of the controls were assayed for insulin-binding capacity. Biopsy samples from the edge of lipoatrophic areas (eight cases) invariably showed abnormal deposition of immunological components in dermal vessel walls, whereas no such deposition was seen in the control samples. Mean serum insulin-binding capacity was 33.1 microgram/l in the patients with lipoatrophy compared with only 4.6 microgram/l in the controls. These findings suggest that insulin-induced lipoatrophy results from the local formation of immune complexes, complement fixation, and release of inflammatory mediators from the cellular infiltrate.     

Partial purification and characterization of the multiple molecular forms of staphylococcal clotting activity (coagulase).

The clotting activity of Staphylococcus aureus strain 104 was purified 46,000-fold, but absolute purity was not achieved. Carbohydrate content of the purified material was not more than 5%. Elution of clotting activity from denaturing and nondenaturing polyacrylamide gels revealed the presence of four distinct molecular forms. Molecular weights of the forms were approximately 31,500, 34,800, 44,800, and 56,800 as determined by gel filtration in 8 M urea, by sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis, and by calculation with determined values for the Stokes radius and sedimentation coefficient. Molecular weights determined on sodium dodecyl sulfate-urea gels were found to decrease as the gel concentration increased, suggesting that the amount of sodium dodecyl sulfate bound was less than normal. Estimated frictional ratios for the forms showed that they differ in shape from one another and that they are all highly asymmetrical. Each of the forms had an isoelectric point between pH 5.44 and 5.47 when focused in 6% polyacrylamide gels for 9 h; however, prolonged focusing altered the isoelectric point of the forms to within the range of pH 4.35 to 4.65. The multiple clotting forms were not artifacts of the purification procedure and did not appear to be products of the proteolytic degradation of a larger protein.     

Lanosterol 14α-demethylase. Similarity of the enzyme system from yeast and rat liver

The chemical synthesis of 24,25-dihydro[32-¹⁴C]lanosterol is described. The incubation of this material with a cell-free system from $\text{Saccharomvoes cerevisiae}$ or with a microsomal preparation from rat liver resulted in both cases in the release of [¹⁴C]formic acid. This result suggests that in the biosynthesis of ergosterol in yeast, as well as in that of cholesterol in higher animals, the 14α-methyl group of lanosterol is removed as formic acid. In both systems, the measurement of the rate of release of [¹⁴C]formic acid from 24,25-dihydro[32-¹⁴C]lanosterol provides a simple and direct assay of lanosterol 14α-demethylase. Carbon monoxide inhibited both yeast and liver 14α-demethylase.     

EMG-biofeedback reduction of tension headache

The biofeedback literature affirms the therapeutic efficacy of EMG-biofeedback-assisted relaxation for the treatment of tension headache. However, this form of therapy has failed to focus on the role of cognitive variables in the control and perception of tension headache. The present case study provides a prototype treatment combining cognitive behavior-modification procedures with EMG-biofeedback training to treat a subject with chronic tension headache. Phase I, baseline, involved collecting mean EMG and daily headache activity, emphasizing specification of environmental stressors. Phase II, cognitive skills-training, focused on:(1) identifying negative self-statements(cognitions) related to stressors, and(2) training the subject to replace negative self-statements with coping self-instructions. This treatment resulted in a 33% headache reduction over baseline, with no concomitant changes in frontalis EMG. Phase III, EMG-biofeedback training, resulted in a 38% reduction in mean EMG level and a 66% reduction in mean headache activity when compared to baseline. The results suggest the importance of attending to cognitive factors in the treatment of tension headache.This paper was presented at the 6th annual meeting of the Biofeedback Research Society, Monterey, California, 1975.