Uptake of radiolabeled ions in normal and ischemia-damaged brain.

The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (63Ni, 99TcO4, 22Na, and [3H]tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of 65Zn, 59Fe, 32PO4, and 147Pm in postischemic brain were similar to or less than those in normal brain. The concentration of [14C]EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that 99TcO4, 22Na, 65Zn, and 59Fe were distributed more uniformly throughout the brain than were 32PO4, 63Ni, and 147Pm. At 24 or 48 hours after ischemia, 63Ni, 99TcO4, and 22Na were preferentially concentrated in the damaged striatum and hippocampus, whereas 65Zn, 59Fe, 32PO4, and 147Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography.

Influence of oxidizing or reducing agents on gastrointestinal absorption of U, Pu, Am, Cm and Pm by rats.

Absorption of 233U, 238Pu, 241Am, and 244Cm from the gastrointestinal (GI) tract was measured in rats, fed ad libitum or fasted, that were gavaged with solutions containing ferric iron, ferrous iron, iron powder, quinhydrone or ascorbic acid. Absorption and retention of all of these actinides was increased substantially by fasting and by the addition of mild oxidizing agents, ferric iron and quinhydrone. In contrast, absorption and retention were decreased to below the fasted level by all the reducing agents except ascorbic acid, which caused diarrhea and an increase in absorption. Absorption of the lanthanide element 147Pm from the intestine of fasted rats was also increased by ferric iron. Some of these actinide elements are polyvalent and are, in some cases, known to be absorbed from the GI tract more readily in their higher oxidation states. This suggested an oxidation-reduction mechanism for the effect of fasting and the action of the chemical agents used. However, the improbability that either 241Am(III) 244Cm(III) or 147Pm is converted to a different oxidation state under these conditions makes that mechanism unlikely. Other explanations are suggested.

Gastrointestinal absorption of metals (51Cr, 65Zn, 95mTc, 109Cd, 113Sn, 147Pm, and 238Pu) by rats and swine.

Adult and neonatal rats and neonatal pigs were gavaged with solutions of metal radionuclides to determine gastrointestinal absorption. Zinc-65 and technetium-95m were well-absorbed by both age groups; chromium-51, cadmium-109, tin-113, promethium-147, and plutonium-238 were not. The quantities of the poorly absorbed metals that were absorbed by neonates were between 4 and 100 times higher than those absorbed by adult rats. Autoradiograms prepared from the entire small intestine of the neonatal rat showed that 109Cd was retained in the duodenum. In contrast, measurements in the piglets showed much higher 109Cd retention in the ileum than in the duodenum. Autoradiograms and radiochemical measurements of 147Pm and 238Pu in both neonatal rats and swine showed the highest level of retention in the ileum. The results indicate that, for most of the metals studied, absorption from the gastrointestinal tract is substantially higher for neonatal than for adult rats.

Distribution of a lanthanide (147 Pm) in vascular smooth muscle.

In order to ascertain whether trivalent rare earth ions such as lanthanum (La+++) penetrate the cell membrane under physiological conditions, the extracellular and cellular distribution of promethium (147 Pm), a carrier-free rare earth radioisotope, was examined in rabbit aortic smooth muscle. As the duration of incubation was lengthened, uptake of 147Pm continued to increase; it was inhibited by La+++ and other rare earth ions (Nd+++, Lu+++) only when the 147 Pm/rare earth concentration ratio exceeded 1:10(6). However, equally high concentrations of Ca++ had no effect on 147Pm uptake. Efflux of 147Pm was only transiently increased by 1.5 mM La+++, and exposure to 0.05 mM EDTA elicited an increased 147Pm efflux with both transient and maintained components. The magnitude of the EDTA-induced increase in 147 Pm efflux was similar over a 30-fold range of EDTA concentration (0.05-1.5 mM); the limiting factor for 147Pm efflux is the rate of 147Pm desorption from the tissue rather than the extracellular concentration of EDTA. Loss of 147Pm in the presence of 0.05 mM EDTA could be described in terms of two specific washout components (the more rapid of which included 147Pm within the extracellular space and the slower of which had half-times of washout of approximately 7-10 minutes). Uptake of 147Pm was inhibited by lowering the incubation solution temperature to 0 degrees C or by procaine. However, concentrations of metabolic inhibitors (iodoacetate and dinitrophenol) which diminish loss of Ca++ from the cell did not decrease either the uptake or efflux of 147Pm. Thus, significant quantities of 147Pm do not appear to be accumulated within the cell or transported out of the cell; distribution of 147Pm can be most simply described in terms of a binding at and desorption from surface acessible fiber sites.