Edward C. Hauer

Intracerebroventricular Administration of Leukocytic Endogenous Mediators (LEM) in the Rat

Summary LEM obtained from glycogen-induced peritoneal exudates in rabbits were injected into the lateral cerebral ventricle of rats to determine if LEM had a primary site of action in the central nervous system. LEM injected icv in the dose of 10, 20, or 50 μl was observed to produce a rapid hy-perthermia. Injection of heated LEM failed to cause a hyperthermic response. Endo-toxin and heated endotoxin (20 ng/20 μl/ rat) administered icv each produced a delayed hyperthermia as compared to LEM. The various doses of LEM were also observed to significantly decrease plasma iron and zinc, increase plasma copper, increase the synthesis of plasma α2 acute-phase protein (α2-MFP), and cause a flux of a nonme-tabolizable amino acid ([14C]AIB) to the liver. These observations suggest that LEM in doses which are inactive systemically can mediate certain effects on or through the central nervous system following icv administration. The authors wish to acknowledge the invaluable technical assistance of Ms. Beverly A. Carter and Mr. Wayne Rill. We are grateful to Drs. Philip Sobocinski and David T. George for their thoughtful discussion.

Relationship between serum chromium concentrations and glucose utilization in normal and infected subjects.

Studies in healthy individuals demonstrate that serum chromium concentrations fall precipitously following the intravenous administration of a 30-gm. glucose load. Significant decreases from baseline control fasting serum Cr concentrations were also observed when intravenous glucose was given during sandfly fever. Glucose disappearance rates also decreased significantly to approximately one half of pre-illness control values while serum Cr values declined still further. In addition, serum Cr disappearance rates could be calculated. When individual preexposure and postexposure serum glucose and Cr disappearance rates were compared, a significant linear correlation was found (P <0.05). Acute infection appears to reduce the availability of circulating Cr, which may contribute to the altered glucose metabolism characteristic of acute infections even in the presence of elevated insulin levels and other hormonal changes.

The direct determination of serum chromium by an atomic absorption spectrophotometer with a heated graphite atomizer.

Abstract By the use of a heated graphite atomizer, serum chromium concentrations can now be measured directly by atomic absorption spectrophotometry in 50-μl serum samples. Pretreatment or tedious extraction procedures of serum samples are avoided by this relatively simple, rapid, and reproducible method. Interference by other metals or salts in serum can be eliminated by this technique of selective volatilization. The coefficient of variability on a single pooled serum sample was 5.8%, and a value of 100.6% was obtained in recovery studies. When serum Cr concentrations were measured in a group of 15 healthy young adults, a mean serum concentration of 1.58 ppb (± SE of 0.08) was obtained. The results obtained can be attributed to the sensitivity of the analytical system, the reduction of possible sources of exogenous contamination, and the elimination of interference by other elements within the sample or system.

Induction of hypozincemia and hepatic metallothionein synthesis in hypersensitivity reactions.

Summary Recent evidence indicates that hypersensitivity reactions, produced in rats by the administration of a protein antigen, alters plasma zinc and iron homeostasis by depressing concentrations of these trace minerals. Studies were performed to determine if altered zinc homeostasis involves, in part, enhanced hepatic metallothionein (MT) synthesis. MT, a high cysteine-containing cytoplasmic protein, possesses a high affinity for zinc and other heavy metals and has been implicated in zinc homeostasis. Antigen challenge (0.5 mg BSA) in rats previously sensitized with either 5 or 10 mg BSA produced a significant decrease in plasma zinc and iron concentrations within 7 hr in an apparent dose-dependent manner. Plasma zinc depression was accompanied by an increase in hepatic MT content as well as MT-associated total Zn and 65Zn used to pulse-label the metalloprotein. The depression in plasma zinc, but not iron, and the enhanced synthesis of MT was significantly reduced by prior treatment of rats with actinomycin D. This finding suggests a requirement for new mRNA synthesis for zinc, but not iron alterations during hypersensitivity reactions. Results support the concept that induction of hepatic MT may be a common mechanism involved in altered plasma zinc homeostasis regardless of the initiating pathophysiologic condition.

An Assay of RNA Synthesis in Hepatic Nuclei from Control and Streptococcus pneumoniae-Infected Rats

Abstract Hepatic nuclei were isolated, purified, and partially characterized from control and Streptococcus pneumoniae-infected rats. Biochemical and morphologic examination showed little contamination by other cell organelles. An in vitro system for the incorporation of 2-[14C]uridine-5′-triphosphate into ribonucleic acid (RNA) was developed and characterized. Although the stimulatory effects of cytosol on incorporation of labeled precursors into RNA have been previously reported, nuclei isolated from the livers of S. pneumoniae-infected rats were stimulated to a significantly greater extent than were nuclei isolated from the livers of control rats. In the presence of cytosol prepared from either control or infected rats, the increased incorporation of labeled precursor into RNA by nuclei isolated from infected rats was observed over broad pH and temperature ranges. The increased activity of infected nuclei was eliminated when albumin was substituted for cytosol, and could not be accounted for by differences in endogenous precursor pool size. These results are consistent with other infection-induced alterations in hepatic RNA and protein synthesis.