A series of studies were performed to determine the relationship between physiologic levels of circulating plasma norepinephrine and epinephrine and human platelet alpha-2 binding site number and the affinity (KD) of these sites for antagonist radioligands. In one study, alpha-2-adrenergic binding site number and affinity were compared using both [3H]yohimbine and [3H]dihydroergocryptine as radioligands. There was good absolute and relative comparison for binding site number, but only a relative relationship for KD. In 46 normal subjects, there was no significant relationship between site number or KD and age, plasma epinephrine, or plasma norepinephrine concentration. Even after plasma epinephrine was raised nearly 20-fold by means of an intravenous infusion for 4 h in seven normal subjects, neither sites (608 +/- 68 vs. 567 +/- 120 sites/platelet) nor KD (2.01 +/- 0.94 vs. 2.14 +/- 1.15 nM) were significantly changed. Similarly, neither sites (445 +/- 55 vs. 421 +/- 53 sites/platelet) nor KD (1.44 +/- 0.29 vs. 2.10 +/- 0.75 nM) were significantly changed in six normal subjects when plasma norepinephrine levels increased during oral administration of prazosin for 1 wk. Thus, in a cross-sectional analysis and after a change in plasma catecholamine concentrations, there was no relationship in normal subjects between platelet alpha-2 binding site number or affinity of these sites for antagonist radioligands and the circulating catecholamine levels to which the platelets were exposed. In a group (n = 7) of patients who lack epinephrine-induced platelet aggregation due to abnormal thrombopoiesis, binding site number was decreased (304 +/- 36 vs. 572 +/- 29 sites/platelet, P less than 0.001) and KD tended to be greater (8.69 +/- 2.44 vs. 5.40 +/- 0.31 nM, P = NS) than in normal subjects (n = 46), despite having similar plasma catecholamine levels. There was no difference in binding site number (491 +/- 116 sites/platelet) and KD (5.61 +/- 0.84 nM) in patients (n = 5) with autonomic insufficiency and low levels of upright plasma norepinephrine when compared with the normal subjects. Two patients were examined before and after the removal of a pheochromocytoma. Their binding site number and KD were normal before the operation and essentially unchanged after the tumor removal and fall of plasma catecholamines. Thus, this study demonstrates that within the physiologic and pathophysiologic range of plasma catecholamines (in men), there is no relationship between the circulating catecholamine concentration and either platelet alpha-2 adrenergic binding site number or the affinity of these sites for antagonist radioligands.

Journal Article PULMONARY RETENTION OF COAL DUSTS Get access P. E. MORROW, P. E. MORROW Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and DentistryRochester, NY 14642, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar F. R. GIBB, F. R. GIBB Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and DentistryRochester, NY 14642, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar H. BEITER, H. BEITER Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and DentistryRochester, NY 14642, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar F. AMATO, F. AMATO Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and DentistryRochester, NY 14642, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar C. YUILE, C. YUILE Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and DentistryRochester, NY 14642, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. W. KILPPER R. W. KILPPER Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and DentistryRochester, NY 14642, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar The Annals of Occupational Hygiene, Volume 26, Issue 2, 1982, Pages 291–307, https://doi.org/10.1093/annhyg/26.2.291 Published: 01 February 1982

Nineteen UF6/UO2F2 inhalation studies were undertaken in purebred, female beagle dogs (N = 16) to examine inter alia, (a) the possible relations of exposure, whole body, lung and renal uranium levels to excretion rates; (b) the threshold U6+ dose and renal concentration for renal injury; (c) the distribution and retention functions for U6+ in major tissues; (d) biochemical indicators of renal injury; and (e) aspects of U-induced tolerance. Each of these issues was investigated in the context of the chemical toxicity of U6+ following brief exposures to 235UO2F2 in the presence or absence of HF (the decomposition products of 235UF6). Both gamma-(235U) and alpha-(234U) counting methods were applied. In nine studies on 5 dogs, UO2F2 was administered intravenously. The major findings from both types of studies include: (1) UO2F2 retention time in the lungs is shorter than for UO3 or uranyl nitrate, viz. greater than 80% translocated with T 1/2 of less than 20 min; (2) the urinary elimination of U6+ follows closely to the ICRP excretion equation; (c) an absorbed dose of approximately 10 micrograms U6+ kg-1 body weight appears to be effective in producing renal injury; (d) a renal concentration of 0.3 micrograms g-1 kidney is close to a threshold concentration for renal injury; and (e) urinary and blood biochemical changes and histopathologic data were acquired and evaluated in both novice and tolerant animals. This report, considers all of these objectives and findings: Those involving biochemical indices and uranium-induced tolerance will be more fully reported elsewhere. In general, the dog studies attest to the usefulness of the intravenous human studies for certain U6+ dose-response data and interface well with new retention data on intravenous uranyl citrate in dogs by Stevens et al.

This human investigation of lead absorption from the lungs utilized two forms of lead, lead chloride and lead hydroxide; the former was used in picogram amounts and the latter at microgram levels. These two species of lead were selected in an attempt to simulate the range of physicochemical properties found in atmospheric lead (urban air). Aerosols labeled with lead-203 were made of comparable aerodynamic size (MMAD 0.25 μm ± 0.1) by using sodium chloride as the deposition-determining aerosol. After brief, mouthpiece exposures, 17 subjects were followed by serial counting with a thoracic array of 12 2-in. scintillation detectors and two 2-in. leg counters, all coupled to single channel analyzers. Serial blood samples were also taken. The two exposure groups showed similar total deposition values (23 vs 26%) and the same biological retention halftimes, viz., 22.6 hr. When the retention data were “corrected” for blood-borne 203Pb, the biological halftimes for lung lead retention averaged 13.1 and 14.2 hr, respectively, and were not significantly different. Blood build-up data were also indistinguishable in the two groups. The authors discuss these findings in relation to other inhalation studies and conclude the collective evidence supports the view that atmospheric lead is rapidly and completely absorbed from the human lungs.

Because levels of glycosylated hemoglobin (GHb) are increased in diabetes and reflect the previous metabolic control, clinicians and clinical investigators are finding increasing applications for measurements of GHb in diabetic patients. We report the characterization of a colorimetrie assay procedure for GHb and compare its performance with that of a commonly used assay by ion-exchange chromatography. Although results of GHb determination by both methods correlate highly (r = 0.943, P < 0.001), the two procedures estimate different glycosylated fractions. The colorimetrie procedure is nonstoichiometric, requiring careful standardization of assay conditions, including the concentration of total hemoglobin in the assayed aliquot, to achieve precision and permit comparison of results. We characterized the effect of storage of hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetrie method, but not by column chromatography, are reproducible on hemoly-sates or packed erythrocytes stored frozen for at least 5 mo. A unique advantage of the colorimetrie procedure is the capability to estimate GHb levels when variant hemoglobins, including fetal and sickle hemoglobins, are present.

Coal dust aerosols with cesium-134 and scandium-46 labels were studied in dogs and rats following brief inhalation exposures by external measurement of gamma photons in the 0.6 to 0.8 and 0.9 to 1.1 MeV regions, respectively. Ancillary in vitro studies of the leaching characteristics of the two radionuclides from coal were made and control studies utilizing the "free" radionuclides were undertaken for each of the investigations with radioactive coal dust. The biological data strongly infer that coal dust retention in canine lungs is extremely protracted with a biological half-life no shorter than approximately 4.3 yr and probably much longer. The biological model which was formulated and analyzed to obtain this finding is discussed along with its limitations.

The lymphatic system of the lungs has proved difficult to study and characterize because it is technically complex to investigate, its properties are difficult to quantitate, and anatomically it is extraordinarily variable. This study was part of a more comprehensive effort to understand the nature of lymphatic permeation by extrinsic materials (e.g., dusts) arising from alveolar deposition, and had three main objectives; (1) to develop a reliable surgical approach for the collection of lymph from the right duct; (2) to investigate some of the inconsistencies in lymphatic structure and function, especially the relationship of the right lymph duct (RLD) and thoracic lymph duct (TLD) outflows to the pulmonic lymph; and (3) to begin a systematic investigation of lymphatic uptake of administered materials by varying their physicochemical parameters. Ultimately, we utilized a modification of the surgical approach of Meyer, which we believe is less prone to blood contamination than the venous-sac procedure of Leeds and Uhley and provides purer pulmonic lymph. By this means we obtained average RLD flow rates of 4.5 ml/h or 0.35 ml/h . kg body weight in 24 dogs, which are comparable to those in the recent literature. For demarcation of the pulmonic drainage in relation to the RLD and TLD, we found in 13 dogs that 75% or more of the lung lymph returned to the venous circulation through the RLD, wheras less than 3% of the thoracic lymph entered the RLD. Radioactive tracers were administered by intralymphatic, intrabronchial, inhalation, and intravenous routes to obtain these findings and the uptake data. Lymphatic uptake values for iron, cadmium, and lead were obtained principally after intrabronchial administration. The uptake data, while preliminary, indicate that both the chemical species and their physical states are important in affecting alveolar permeation into the pulmonic lymph. Evidence for varying lymphatic roles in the alveolar retention of these heavy metals is also presented.

Uranium dioxide (UO2) and uranium trioxide(UO3), in biological terms, are prototype U+4 and U+6 compounds, respectively. The intramuscular injection studies performed in rats described in this report were designed to complement previously reported inhalation studies in dogs and certain “in vitro solubility” assessments of these same materials. The intramuscular retention functions of the two U-235 enriched uranium oxides were found to resemble closely those determined for the lungs; specifically, for UO3: R(muscle) = A0e−0.165t + B0e−0.017 versus R(lungs) = A0e−0.0038t + B0e−0.023t; and for UO2: R(muscle) = A0e−0.0044t versus R(lungs) = A0e−0.0038t where A0 and B0 represent fractional retentions whose sum is 1.0 and t is expressed in days. A single rabbit study with intramuscular UO2 gave a confirmatory retention half time of 172 days.