Nuclear and cytoplasmic localization of basic fibroblast growth factor in astrocytes and CA2 hippocampal neurons.

Fibroblast growth factors (FGFs) are known to stimulate mitogenesis in a variety of non-neuronal cell types and to support the survival in vitro of many neuronal cell types. The physiological role of FGFs in the CNS is currently not known. The present study determined the distribution in the rat CNS of a prominent member of the FGF family, basic FGF (bFGF). Immunohistochemical analysis showed that bFGF immunoreactivity was found predominantly in astrocytes throughout all regions of the CNS. In contrast, only a few neuronal populations were found to contain bFGF immunoreactivity, most prominent among them, neurons in the CA2 area of the hippocampus. This predominant localization of bFGF to astrocytes was confirmed by two other observations: (1) highly enriched cultures of astrocytes contained bFGF immunoreactivity and bioactivity, whereas highly enriched cultures of cerebral cortical neurons contained no detectable bFGF, and (2) neonatal rat cerebral cortex, which contains only a few differentiated astrocytes, also contained no detectable bFGF immunoreactivity and only low amounts of bFGF bioactivity. Immunocytochemical analysis also suggested that bFGF immunoreactivity was present in the nucleus as well as the cytoplasm of astrocytes and CA2 neurons. This nuclear localization was confirmed by EM analysis of the intracellular distribution of the immunoperoxidase reaction product. In addition, preparations of both nuclear and soluble fractions of brain extracts contained bFGF immunoreactivity and bioactivity. These data suggest that bFGF might be involved in mediating astrocytic influences on the late postnatal maturation and plasticity in the CNS, and that the nuclear localization of bFGF within astrocytes may play an important role in the differentiation of these cells. In addition, bFGF may play a similar role in a few specific neuronal populations, such as CA2 hippocampal neurons.     

Sumatriptan blocks spreading depression in isolated chick retina

Spreading depression is a neurohumoral phenomenon that has been related to the pathophysiology of migraine. The recently introduced 5HT_1D agonist anti-migraine compound sumatriptan blocks neurogenic extravasation and induces cerebral vasoconstriction, but the actual mechanism of action against migraine remains obscure. Retinal spreading depression (RSD) velocity has been measured in isolated chick retinas in the presence of 0.05-2.00:nM sumatriptan. This drug reversibly blocks RSD in a concentration-dependent manner. Since the preparation is blood-vessel free, this effect must be related to the nervous tissue.     

Cause of signal loss in MR images of old hemorrhagic lesions

Old hemorrhagic lesions in the brain are characteristically surrounded by a band of hemosiderin-containing tissue. This region is typically of low signal intensity on long-echo-time (TE) radio-frequency (RF) spin-echo magnetic resonance (MR) images and on gradient-echo MR images. To determine the cause of signal loss in this band, the authors measured the signal that arises from imaging such a region with use of an RF spin-echo technique with a 180 degrees pulse incrementally displaced from TE/2. The incremental loss of signal was small. Using an agar phantom containing iron particles, the authors also showed that signal loss results primarily from diffusion in magnetic gradients. They conclude that most signal loss in the dark band surrounding areas of late-stage hemorrhage arises from diffusion in areas of magnetic inhomogeneity.     

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses

A randomized double-blind, cross-over study using treatment periods of 12 weeks with a 2-week washout, comparing two long-acting formulations of propranolol ('Inderal' LA 160 mg daily and Half-'Inderal' LA 80 mg daily) was performed after a placebo run-in of 4 weeks on 51 patients. The study indicated that both long-acting formulations were significantly better than placebo in reducing the frequency of migraine attacks (p less than 0.01). After 12 weeks there was a significantly lower (p = 0.03) frequency of migraine attacks in patients on the higher dose formulation than in those on the lower dose formulation. There was no significant difference in the frequency of side effects produced by the two formulations.     

An evaluation of intravenous immunoglobulin in the treatment of human immunodeficiency virus-associated thrombocytopenia

BACKGROUND: Anecdotal evidence suggests that high-dose intravenous immunoglobulin (IVIG) is useful in the management of human immunodeficiency virus (HIV)-associated thrombocytopenia. STUDY DESIGN AND METHODS: To rigorously evaluate this therapy, a crossover study was designed to compare IVIG, given at 1 g per kg per day for 2 consecutive days each week for 4 weeks, with intravenous saline placebo administered according to the same schedule. Subjects were randomly assigned to receive either IVIG or saline during the first 4 weeks; if IVIG was given, there was a 4-week period of no therapy before beginning placebo administration. Criteria for eligibility were platelet count of less than 50,000 per microL (50 × 10(9)/L), elevated platelet-associated IgG levels, increased megakaryocytes in the bone marrow, and positive HIV antibody test. Twelve patients (11 men, 1 woman) were studied. Seven patients completed the full protocol. Four dropped out: after 2, 5 (2 patients), and 8 weeks that included at least 2 weeks of IVIG. RESULTS: All patients sustained an increase in platelet count in response to IVIG, with increments ranging from 15,000 to 358,000 per microL (15 to 350 × 10(9)/L) (mean, 180,000/microL [180 × 10(9)/L]; median, 174,000/microL [174 × 10(9)/L]). No patient had an increase after placebo infusions. There were no adverse effects of treatment, and weekly chemical analyses showed no new abnormalities except for mild elevations in the serum protein. The duration of responses ranged from 2 to 10 weeks. No patient demonstrated refractoriness to IVIG. CONCLUSION: IVIG consistently raises platelet counts in patients with HIV-associated thrombocytopenia.     

The One Year Incidence of Postoperative Myocardial Infarction in an Orthopedic Population

The diagnosis of a postoperative myocardial infarction (PMI) is important in the orthopedic population because these events can be associated with significant cardiac morbidity. Plasma troponin I (cTnI) analysis has markedly increased our ability to detect myocardial damage. Using cTnI analysis for evidence of a PMI, we prospectively assessed all of our patients for (1) the 1-year incidence of PMI, (2) the clinical consequences of a PMI in relation to the level of the cTnI release, and (3) 6-month follow-up for cardiac complications. During a 12-month period, patients at risk for perioperative myocardial ischemia were assessed for a PMI by serum cTnI levels and daily serial ECGs. Patients with cTnI levels above the reference level (≥0.4 ng/ml) were also assessed for new cardiac regional wall motion abnormalities with an echocardiogram and 6-month postdischarge adverse cardiac events. Of the 758 patients who were assessed for a PMI, 49 patients had detectable cTnI levels (≥0.4 ng/ml); the incidence of a PMI was 0.6% of all surgical cases and 6.5% of those patients were at risk for a cardiac event. A PMI was more common after hip arthroplasty than other orthopedic procedures. Twenty-three patients had a cTnI level >3.0 ng/ml, and 74% these patients (17/23) had anginal symptoms and/or ischemic ECG changes. Nine of these patients (9/23) had new postoperative echocardiographic changes, five (5/23) required emergency transfer to a cardiac care unit, and 10 (10/23) had postoperative cardiac complications. In contrast, 15 patients with levels of cTnI <3.0 ng/ml and without ischemic ECG changes and/or anginal symptoms had no postoperative cardiac complications. Fourteen patients (14/47) had cardiac complications 6 months after discharge, including four cardiac deaths, one fatal stroke, and four patients with unstable anginal episodes that required a change in medical management, and six patients required coronary revascularization. Orthopedic surgical patients with cTnI level <3 ng/ml and without symptoms or ECG changes suggestive of myocardial ischemia (15/49) may have different risks than those with higher-level cTn1. This study was funded by the Department of Anesthesiology, Hospital for Special Surgery, New York, NY.     

Influence of the vitamin D hormonal status on the hepatic response to bromobenzene

Hypocalcemic vitamin D-depleted rats received either 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] or calcium p.o. in order to study the effects of plasma calcium normalization, resulting from hormone or dietary calcium administration, on the hepatic response to bromobenzene (BB). Results showed that 1,25(OH)2D3 administration induced a rise in the circulating aspartate aminotransferase, alanine aminotransferase and sorbitol dehydrogenase after BB administration significantly greater than in unsupplemented rats. The volumic density of necrosis was not, however, increased by 1,25(OH)2D3 whereas the proportion of acidophilic cells surrounding the necrotic area and the ratio of acidophilic to necrotic cells were significantly increased suggesting the presence of regenerating parenchyma. Oral calcium yielded an increase comparable to that of 1,25(OH)2D3 in apparent BB toxicity which was accompanied by a significant rise in both the volumic density of necrosis and of acidophilic cells but the ratio of acidophilic to necrotic cells was not increased by dietary calcium. The amount of cytochrome P-450 lost after BB administration, the covalent binding of BB metabolites to cellular proteins in vitro and the total liver glutathione content were not changed by either 1,25(OH)2D3 or calcium supplementation. Results show that hypocalcemic vitamin D-depleted rats are protected partially against BB toxicity; this protection does not seem to be due to a decrease in the hepatic metabolism of BB but seems to be related to the hypocalcemic state; on the other hand, the active regenerating process which seemed more apparent in 1,25(OH)2D3-treated than in all other animals may have contributed to offset partly the cellular damage induced by the toxin in the hormone-treated group.