Copper radionuclides and radiopharmaceuticals in nuclear medicine

The chemistry, radiochemistry, radiobiology, and radiopharmacology of radiopharmaceuticals containing copper radionuclides are reviewed. Copper radionuclides offer application in positron emission tomography, targeted radiotherapy, and single photon imaging. The chemistry of copper is relatively simple and well-suited to radiopharmaceutical application. Current radiopharmaceuticals include biomolecules labelled via bifunctional chelators primarily based on cyclic polyaminocarboxylates and polyamines, and pyruvaldehyde-bis(N⁴-methylthiosemicarbazone) (PTSM) and its analogues. The chemistry of copper, of which only a fraction has yet been exploited, is likely to be applied more fully in the future.     

The Complex Nature of Interactive Neuroregeneration-Related Molecules

We review the growing list of molecules that may be involved in wound healing in the central nervous system (CNS). It is known that many of these molecules are present during normal development and neoplastic growth in both neural and nonneural tissues, often in areas where pattern formation or tissue remodeling is evident; however, their functional roles are often quite elusive. In order to understand the changes that occur in and around a brain wound, we review proposed functions of neuroregeneration-related molecules in in vitro and in vivo preparations, as well as note their expression in other healing tissues including skin. A hypothesis that wound healing events in the CNS supersede neuritic growth around a lesion is presented. In contrast to the classical view of failed regeneration, there may be significant amounts of circuit reorganization that occur following injury, and such plasticity may be further enhanced by manipulating the molecular environment around a brain wound and in synaptically related structures.     

Risk of developing AIDS in HIV-infected cohorts of hemophilic and homosexual men

The latency period and/or incidence of the acquired immunodeficiency syndrome (AIDS) may differ in persons infected with the human immunodeficiency virus by different routes or having different "cofactors." We compared 79 hemophilic men in Pennsylvania and 117 homosexual and bisexual men in California, all having known dates of infection and long postinfection observation periods, to examine these hypotheses. By 1987, twenty-one percent of the hemophilic and 27% of the homosexual men had developed AIDS. However, seroconversion patterns differed for the two groups, and when this was taken into account, the conditional odds ratio for AIDS was 1.20. Kaplan-Meier survival analysis showed no significant difference in the cumulative proportion with AIDS, from time of infection. These results are limited by the small size and geographically localized nature of our study populations, but they suggest that currently the relative length of human immunodeficiency virus infection is of primary importance in comparing disease outcome for different populations.     

Inhibitory effect of amiloride and gadolinium on fine afferent nerves in the rat knee: evidence of mechanogated ion channels in joints

Synovial joints are complex sensory organs which provide continuous feedback regarding position sense and degree of limb movement. The transduction mechanisms which convert mechanical forces acting on the joint into an electrochemical signal which can then be transmitted to the central nervous system are not well understood. The present investigation examined the effect of the mechanogated ion channel blockers amiloride and gadolinium on knee joint mechanosensitivity. In deeply anaesthetised rats (sodium thiopental: 100–120 mg/kg, i.p.), single unit extracellular recordings were made from knee joint group III (Aδ) and group IV (C) primary afferents in response to mechanical rotation of the joint. Afferent firing rate was measured before and after topical application of either amiloride (0.1 mM, 1 mM) or gadolinium (250 μM) onto the receptive field of the sensory unit and recording was continued every 10 min up to a total of 50 min. With normal rotation of the knee, joint mechanosensitivity was significantly reduced by both amiloride (P<0.0001; n=10–21) and gadolinium (P=0.001; n=12) and this effect was sustained throughout the recording period. This investigation provides the first in vivo electrophysiological evidence that joint mechanotransduction involves the activation of amiloride and gadolinium-sensitive mechanogated ion channels. Future studies to determine the mechanogated ion channel subtypes present in joints and the modulation of their gating properties during inflammation may yield novel approaches for the control of arthritis pain. Funding: JJMcD is funded by the Alberta Heritage Foundation for Medical Research, the Canadian Institutes for Health Research, and the Arthritis Society of Canada.