Biodistribution of64Cu in inflamed rats following administration of two anti-inflammatory copper complexes

⁶⁴Cu was administered in two anti-inflammatory formulations to normal rats and to rats with 2 forms of local inflammation, namely (a) an acute paw oedema (elicited with carrageenan) or (b) a chronic granulomatous response to an implanted irritant (Mycobacterium tuberculosis in a polyurethane sponge). The copper formulations used were (i) a slow release one consisting of Cu(II) salicylate applied dermally with ethanol/DMSO and (ii) short acting hydrophilic complex (Cu(I)Cu(II)-penicillamine)^5– given subcutaneously.Three types of changes in copper biodistribution with these forms of inflammation were discerned based on determination of⁶⁴Cu and copper content in the following organs: inflammatory locus (foot or sponge implant), kidney, liver, spleen, adrenals, brain, blood, thymus, heart, and skin (site of application). The most evident changes were in the kidneys, liver, spleen, adrenals, thymus and serum from animals with chronic granulomatous inflammation. In contrast, a short term acute inflammatory stress (carrageenan paw oedema) had little effect.While copperd-penicillamine (applied subcutaneously) appeared to move as a bolus through the animals, the results with the percutaneous copper salicylate formulation are consistent with it providing a slow release source of copper(II). Exogenous⁶⁴Cu from both formulations was sequestered at inflammatory sites (relative to serum). This may partly explain how applied copper complexes can be anti-inflammatory.     

Radionuclide Quantitation of Left-to-Right Cardiac Shunts in Children

Summary: In order to evaluate the clinical usefulness of radionuclide methods measuring the magnitude of left-to-right cardiac shunts, a comparison has been made of the results obtained using these procedures with those estimated by cardiac catheterization. Seventy children in whom the presence or absence of a shunt had been established, were studied. Two methods for radionuclide shunt quantitation, the pulmonary to systemic blood flow ratio (Qp/Qs) of Maltz and Treves and their modified C2/C1, were evaluated. The former was found to be superior and showed a high correlation of shunt size with the catheter results. With attention to the performance of the investigation and in the data analysis, good discrimination can be achieved between normal patients and those with shunts. Because of the atraumatic nature of the investigation, it is concluded that the procedure is of value in the diagnosis of a cardiac murmur, the assessment of post- operative patients and the follow-up of patients known to have a small shunt.     

Biologically active derivatives of fatty acids

The causal role assigned to the E and F prostaglandins in inflammatory processes, implied by the antiinflammatory action of prostaglandin synthetase inhibitors, is not consistent with the findings reported here that a compound (MK-447) capable of increasing levels of these prostaglandins is antiinflammatory in classical animal models of acute inflammation. That both MK-447 and prostaglandin synthetase inhibitors depress the enzymatic formation of PGG₂ from arachidonic acid suggests that this endoperoxide plays a pivotal role in acute inflammation. However, in view of the intermediate nature of PGG₂, it seems likely that such a pivotal role for this substance is a function of its ability to be converted to other inflammatory mediators. Possible candidates for a causal role are thromboxane A₂ (TXA₂) prostacyclin (PGI₂), both of which derive from PGG₂. However, direct evidence is presented to show that an oxygen equivalent released in the enzymatic conversion of PGG₂ to PGH₂ is a prime factor in inflammation.