Rate of uptake of lead-203 into brain and other soft tissues of the rat at constant radiotracer levels in plasma.
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Biomedical subjects
Publications and source records attributed to R Deane.
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The hypothesis was investigated that colloidal ferric or aluminum hydroxides, formed in blood plasma in vivo, potently absorb lead and thus profoundly influence uptake of lead into certain soft tissues. Rats were given 203Pb i.v. to obtain a near constant plasma level of 203Pb. Tissue uptake of 203Pb at 1 hr was determined with and without the i.v. infusion of 5.0 mM ferric chloride or 5.0 mM aluminum chloride. Infusion of Fe chloride or Al chloride suppressed the uptake of 203Pb into brain, cerebrospinal fluid, skeletal muscle, kidney and red cells by 70 to 94%. In contrast, the uptake of 203Pb into liver and spleen was not significantly reduced, in the case of spleen being greater after Fe chloride or Al chloride infusion. The latter increases were not statistically significant. After ultracentrifugation, greater than 70% of plasma 203Pb activity was associated with the hydroxide-protein pellet (Fe chloride and Al chloride experiments). The ultrafilterable 203Pb in such sera was reduced by greater than 90% compared with controls. By the use of the lead electrode in vitro, lead adsorption to ferric hydroxide was confirmed. Thus, in vivo formation of colloidal hydroxides must occur under the authors' conditions, leading to a reduction of ionized lead in plasma and lower uptake where this depends on free lead and comparable or enhanced uptake into tissues containing reticuloendothelial cells capable of phagocytosis.
The blood-perfused choroid plexuses from the lateral ventricles of the sheep were used to determine the nature of sugar exchanges between blood and cerebrospinal fluid (c.s.f.). There was a net entry of sugars from blood to c.s.f. at all concentrations of sugars which were used and this net entry was seen when the sugars were measured either directly by enzymic analysis or by the use of isotopically labelled sugars. From competition experiments the order of affinity of the transporting system from both blood to c.s.f. and c.s.f. to blood was the same, i.e. 2-deoxy-D-glucose much greater than D-glucose greater than 3-O-methyl-D-glucose much greater than D-galactose. The transport of sugars from c.s.f. to blood and blood to c.s.f. consists in both cases of a non-saturable and a saturable component. However, the affinity of the two systems is markedly different, the blood to c.s.f. being a system of low affinity and high capacity while that of the c.s.f. to blood has a high affinity and a low capacity. The concentration of glucose in the newly formed c.s.f. was estimated from the rate of c.s.f. secretion and the net flux of glucose across the choroid plexus. The concentration of glucose in this fluid was some 45-60% of that in plasma and so the low glucose concentration observed in bulk c.s.f. would appear to be a result of the entry process and not that of cerebral metabolism.
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This report presents data obtained in the care of 830 patients requiring assisted ventilation. When these patients were divided into groups by the severity of their respiratory failure as defined by the duration of ventilatory assistance (greater than 48 hours, less than 48 hours) and level of positive end expiratory pressure (PEEP) required (greater than 5 cm HoH, less than 5 cm HoH), it was found that evidence of concurrent bacterial infection was present in the majority of patients with severe respiratory failure. This finding could not be explained by infection acquired after the onset of respiratory failure. In addition, this analysis demonstrated the important association of active pulmonary infection with the occurrence of barotrauma in these patients. Case analysis of patients subjected to extracorporeal membrane oxygenation has led to the suggestion that underlying sepsis in patients failing to respond to conventional ventilatory assistance similarly limits the usefulness of membrane oxygenator support.
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This review examines the kinetics and possible mechanisms of lead transport into brain across the microvessel endothelium (the blood-brain barrier). Although severe lead poisoning both in neonatal rats and in young children may cause microvessel damage, there is little evidence that there is either damage or even disturbance of specific transport mechanisms at blood leads < 80 micrograms/dl. When 203Pb was continuously infused intravenously into adult rats, radiotracer uptake into different brain regions was linear with time up to 4 hours, reaching spaces in relation to plasma of 6.6 - 8.2 ml/100 g in cerebral tissues at one hour. The concentration of free Pb+ in serum is of the order of 10(-12)M, the majority of lead being bound to protein and to sulfhydryl compounds, such as L-cysteine. Transport into brain has been further studied during short vascular perfusion of one cerebral hemisphere of the rat with oxygenated and buffered physiological saline. This allows total control of the fluid perfusing the cerebral microvessels. In the absence of organic ligands for lead, 203Pb entered brain very fast, with a space of 9.7 ml/100 g in frontal cortex at one min. The presence of albumin, L-cysteine or EDTA abolished measurable uptake. Experiments designed to reveal a role for the anion exchanger or calcium channels gave negative results. However, the effects of potassium depolarization and of varying pH indicated that the lead species passively entering the endothelium might be PbOH+. Experiments with various metabolic inhibitors, including vanadate, suggested that Pb uptake in the endothelium is mitigated by active back transport of lead into blood by the Ca-ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)