Recent Publications by CFE Educators

Intramuscular injections of gold sodium thiomalate in the rat produce a significant depletion of the proinflammatory neuropeptide substance P (SP) from the sciatic nerve. The greatest reduction in SP content occurred during the first two months of treatment. The level of SP in the nerve, however, remained low, throughout an eight month administration of gold. These results, coupled with previous findings that gold produces a selective decrease in the number of unmyelinated axons in peripheral nerve, are consistent with the hypothesis that the anti-inflammatory action of gold involves a neurotoxic effect on peptidergic afferents.

In this triple-label, electron microscopic study in the rat, a lesion of the midbrain periaqueductal gray (PAG) was made so that the distribution and targets of degenerating PAG terminals could be identified in the medullary nucleus raphe magnus (NRM). Spinally projecting NRM neurons were identified by the retrograde transport of wheat germ agglutinin-horseradish peroxidase from the cervical cord. We also used immunocytochemistry to define the subpopulation of NRM neurons which were serotonin-immunoreactive. We report that both serotonergic and non-serotonergic neurons of the medulla, which project to the spinal cord, receive monosynaptic inputs from the PAG.

Bronchoalveolar lavage has been used to sample cells and proteins in the distal lung. One of the major secretory products of the alveolar type II epithelial cells, pulmonary surfactant, can be recovered by lavage. Abnormalities in alveolar type II cells are found in biopsies of patients with idiopathic pulmonary fibrosis (IPF), and abnormalities of pulmonary surfactant phospholipids have been reported after diffuse lung injury in animals and in humans. Therefore, we questioned if abnormalities in lavage phospholipids might also occur in IPF, a chronic inflammatory disease of the alveolar epithelium and interstitium, and, if present, would these abnormalities reflect histopathologic changes or predict responsiveness to therapy. Fifteen untreated patients with IPF, diagnosed by open lung biopsy, were studied and were found to have less than half the amount of bronchoalveolar lavage phospholipid as that recovered from healthy volunteers (p less than 0.05). In addition, patients with IPF had a lower proportion of phosphatidylglycerol and a higher proportion of phosphatidylinositol in the recovered phospholipids than did healthy volunteers (p less than 0.05). The severity of these alterations in phospholipid composition correlated with more advanced fibrotic histopathologic changes. Patients with less depression of total phospholipids in lavage improved with corticosteroid therapy, whereas the patients with more severely decreased total phospholipid recovered in lavage did not.

Newly developed colloid volume-expanding agents with mean molecular weights lower than currently available agents may improve outcome after stroke with fewer allergic and coagulation system side effects. The smaller molecule, however, may exacerbate ischemic cerebral edema if it accumulates in areas where ischemia has damaged the blood-brain barrier. We administered low-molecular-weight hydroxyethyl starch to rabbits after embolic infarction and measured specific gravity and total water content. We found evidence of ischemic edema in the hemisphere ipsilateral to the embolic arterial occlusion, but the measures of edema were not different in treated and control groups. Of those rabbits suffering severe neurologic deficit, mortality was 2 of 13 in the treated compared with 7 of 12 in the control groups (p less than 0.01). Thus, hemodilution with low-molecular-weight hydroxyethyl starch did not exacerbate cerebral edema and may have improved survival in this model.

This study examined the distribution of immunoreactive dynorphin neurons in the lumbar dorsal horn of unilaterally deafferented, colchicine-treated rats. Ipsilateral to a multiple dorsal rhizotomy there was a significant increase both in the number and intensity of staining of dynorphin-immunoreactive cells in laminae I, outer II and V. A comparable change was seen in animals that were deafferented by sciatic nerve section. Enkephalin immunoreactivity was not altered under these conditions. These results indicate that many forms of injury, not all of which result in increased nociceptive input, can increase the level of dynorphin in spinal cord neurons.

Although there is considerable evidence that the analgesic action of electrical brain stimulation is mediated in part by serotonergic (5-HT) axons in the dorsolateral funiculus (DLF) of the spinal cord, studies in the rat have questioned the existence of this pathway. In this study, we used antisera directed against a conjugate of 5-HT and bovine serum albumin (BSA) to identify immunoreactive 5-HT axons in the DLF of the rat and cat. Both light and electron-microscopic studies were performed so that the fiber caliber of the labeled axons could also be determined. We found a rich complement of immunoreactive 5-HT axons in the DLF of both rat and cat. Although these could be seen without difficulty in the normal cat, in the rat it was necessary to make a lesion of the DLF to build up the staining rostrally. Ultrastructural analysis established that almost all of the labeled axons (in rat and cat) were unmyelinated. We conclude that there are indeed 5-HT immunoreactive axons in the DLF of the rat and cat. These presumably derive from neurons of the medullary nucleus raphe magnus (NRM), which have been implicated in the descending controls exerted by opiates and electrical brain stimulation. The results suggest that previous physiological studies of the properties of the opiate-responsive, spinally projecting NRM neurons were not made from those that are 5-HT containing.

Spinal serotonin1 (5-HT1)(labelled by [3H]5-HT), 5-HT1A (labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT)), mu- (labelled by [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol ([3H]DAGO) and [3H]naloxone) and delta-opiate (labelled by [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr [( 3H]DSTLE] receptor binding sites were studied in adult rats using quantitative autoradiography after either neonatal treatment with capsaicin or unilateral cervical dorsal rhizotomy. Both treatments produced a significant loss of 5-HT (-20 to -30%) and opiate (-30 to -45%) binding sites within the superficial layers of the dorsal horn, suggesting they are partly located presynaptically on primary afferent fibres. Thus, 5-HT, as well as opiates, might generate analgesia by acting--at least partly--on primary afferent nociceptive fibres at the spinal level.

This study examined the medullary distribution of peptide-containing neurons at the origin of bulbospinal pathways in the rat. Antisera directed against substance P, methionine-enkephalin-arg-gly-leu and dynorphin B were used on sections in which spinally projecting brainstem neurons had been identified by the retrograde transport of a protein-gold complex that was injected into the spinal cord. Both the relative numbers and distribution of the different peptide-immunoreactive spinally projecting neurons differed. Methionine-enkephalin-immunoreactive neurons were twice as numerous as the substance P-immunoreactive cells and seven times more numerous than the dynorphin B-positive neurons. The methionine-enkephalin cells were found in all medullary raphé nuclei, and in the ventromedial and ventrolateral medullary reticular formation. Caudally, the methionine-enkephalin cells were concentrated laterally; more rostrally they were located more medially. Three major loci of methionine-enkephalin-immunoreactive cells were found: (1) the nucleus reticularis paragigantocellularis lateralis, at levels caudal to the facial nucleus, (2) the B3 cell group (nucleus raphé magnus and the nucleus reticularis magnocellularis, pars alpha) and the most rostral part of the B1 and B2 cell groups (nuclei raphé pallidus and obscurus), (3) a dense cluster of cells that flanks the dorsal surface of the dorsal accessory olive (referred to as the nucleus interfascicularis hypoglossi, pars dorsalis). Substance P-like cells were seen in all raphé nuclei except for the most anterior portion of the B3 cell group. Substance P-immunoreactive cells were also seen in both the ventromedial (nuclei reticularis ventralis and magnocellularis) and ventrolateral medulla (nucleus reticularis paragigantocellularis lateralis). Finally there was a dense concentration of substance P neurons in the nucleus interfascicularis hypoglossi, pars ventralis. The distribution of dynorphin-immunoreactive neurons differed significantly from that of methionine-enkephalin and substance P. Dynorphin cells were almost exclusively found in the ventrolateral medulla (nucleus reticularis paragigantocellularis lateralis), at all levels between the lateral reticular nucleus and the caudal pole of the facial nucleus. The proportion of each of these peptidergic-immunoreactive cells at the origin of bulbospinal pathways differed considerably. Substance P spinally projecting neurons were more numerous than methionine-enkephalin spinally projecting neurons.(ABSTRACT TRUNCATED AT 400 WORDS)