Exo-focal postischemic neuronal damage in the rat brain: alteration of [H]forskolin binding using in vitro autoradiography

We studied the alteration of intracellular signal transduction using quantitative autoradiography of the second messenger system in order to clarify the mechanisms of delayed neuronal damage in the remote areas of rat brain after transient focal ischemia. Chronological changes of [³H]forskolin binding sites were measured to demonstrate the striatal-nigral pathway after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks and 4 weeks of recirculation. [³H]Forskolin binding sites were found to be markedly decreased in the lateral segment of the caudate putamen supplied by the occluded MCA after 90 min of ischemia with no recirculation. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, marked reduction of [³H]forskolin binding sites was observed in the ipsilateral substantia nigra which lay outside the ischemic areas. This postischemic delayed phenomenon observed in the substantia nigra developed concurrently with ⁴⁵Ca accumulation, which was detected there in our previous study. The delayed reduction of [³H]forskolin binding sites in the substantia nigra observed in the present study indicates that striatonigral terminal degeneration at presynaptic sites is caused by precedent ischemic damage of the ipsilateral caudate putamen and that exo-focal postischemic neuronal death is caused by a transsynaptic process associated with the ischemic foci.     

Anorexia nervosa with neutropenia--response of neutrophils to G-CSF]

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.     

Inhibition by indomethacin of spontaneous mammary tumorigenesis in SHN mice

This experiment was designed to examine the effects of indomethacin, a potent prostaglandin synthesis inhibitor, on spontaneous mammary tumors in mice. The growth of established mammary tumors and the appearance of new tumors in multiparous SHN mice were significantly suppressed by the subcutaneous implantation of pellets of indomethacin diluted to 1/12 with cholesterol. Furthermore, the same treatment inhibited normal and preneoplastic mammary gland growth in virgin SHN mice. The pattern of estrous cycles, ovarian structure, and plasma prolactin levels were not affected significantly by the treatment. All results have demonstrated that indomethacin inhibits mammary tumorigenesis of mice primarily by route(s) other than the endocrine system under the present experimental conditions. Indomethacin would be the first agent that appears to inhibit the growth of spontaneous mammary tumors of palpable size in mice.