WIN 63480, a hydrophilic TCP-site ligand, has reduced agonist-independent NMDA ion channel access compared to MK-801 and phencyclidine

NMDA channel blockers are potentially advantageous therapeutic agents for the treatment of ischemia and head trauma, which greatly elevate extracellular glutamate, because they should most effectively inhibit high levels of receptor activation. A novel high affinity TCP site ligand, WIN 63480, does not produce MK-801- or PCP-like behavioral activation at anti-ischemic doses. While WIN 63480, MK-801 and PCP were all observed to be effective blockers of open NMDA channels, WIN 63480 had much less access to closed NMDA channels. This difference may be due to the fact that WIN 63480 is hydrophilic (logD = -4.1) while MK-801 and PCP are lipophilic (logD = +1.8). In vivo, closed channel access may result in a non-competitive profile of antagonism for MK-801 and PCP compared to a more uncompetitive profile for WIN 63480. Release of glutamate, and depolarization, are likely to produce a high level of NMDA receptor activation in ischemic areas compared to normal tissue. Consequently, at anti-ischemic doses, WIN 63480 may produce less inhibition of physiological NMDA-mediated processes in neural systems involved in behavioral regulation than MK-801 or PCP, leading to an improved side effect profile.     

Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders

Deficits in slow-wave sleep (SWS), or delta sleep, are frequently seen in schizophrenia, but their relationship with schizophrenic symptomatology remains unclear. We examined the association between visually scored and automated measures of SWS and positive and negative symptoms in a series of unmedicated patients with schizophrenia and related psychotic disorders. Total and average automated delta wave counts were significantly inversely associated with negative symptoms overall, and the psychomotor poverty syndrome in particular. Total delta counts were also inversely related to the disorganization syndrome. No relation was seen between reality distortion or the Brief Psychiatric Rating Scale (BPRS) positive symptoms and SWS. These findings support the view that SWS deficits may be related to negative symptoms of schizophrenia and may perhaps be mediated by impaired functioning of frontothalamic neural circuits.     

Isolation, cell culture, and characterization of oviduct epithelial cells of the cow

This report describes an easy method of isolation and cell culture of the epithelial cells of cow oviduct. Incubation of cow oviduct with 0.1 mg/ml collagenase in the lumen for 90 minutes helped to dislodge large numbers of ciliated and secretory epithelial cells. The isolated cells, when seeded on plastic, proliferated very quickly and became confluent in 8-10 days in 35 mm Petri dishes. The isolated ciliated cells which attached to the plastic dish lost their cilia after 4-5 days in culture. The cultured epithelial cells were keretin positive. The isolated bovine oviduct epithelial cells, when cultured on plastic precoated with 10 mg/ml matrigel, organized themselves into hollow tubes or spheres with microvilli directed towards the lumen. The epithelial cells seeded on 2 mg/ml matrigel became subconfluent in 15-20 days after seeding. The histoarchitecture of the secretory cells growing in vitro on matrigel resembled that of intact oviduct secretory epithelial cells. Occasional ciliated cells containing large number of mitochondria were observed in the monolayer cultured on 2 mg/ml matrigel substratum but possessed few cilia. The oviduct epithelial cells cultured on 2 mg/ml matrigel incorporated 35S-methionine linearly into protein up to 8 hours in the presence of estradiol or progesterone. The fluorograph of the newly synthesized proteins indicated the presence of an additional 60 kd protein in the cell extract of epithelial cells incubated with estradiol.     

Cytoskeletal-associated protein kinase and phosphatase activities from cerebral cortex of young rats

We describe the phosphorylation system associated with the Triton-insoluble cytoskeletal fraction that phosphorylates in vitro the 150 kDa neurofilament subunit (NF-M) and alpha and beta tubulin from cerebral cortex of rats. The protein kinase activities were determined in the presence of 20 microM cyclic AMP (cAMP), 1 mM calcium and 1 microM calmodulin (Ca2+/calmodulin) or 1 mM calcium, 0.2 mM phosphatidylserine and 0.5 microM phorbol 12,13-dibutyrate (Ca2+/PS/PDBu). Phosphorylation of these cytoskeletal proteins increased approximately 35% and 65% in the presence of cAMP and Ca2+/calmodulin, respectively, but was unaffected in the presence of Ca2+/PS/PDBu. Basal phosphorylation of these proteins studied increased approximately 35% and 72% in the presence of 0.5 microM okadaic acid and 0.01 microM microcystin-LR, respectively, suggesting the presence of phosphatase type 1. Results suggest that at least two protein kinases and one protein phosphatase are associated with the Triton-insoluble cytoskeletal fraction from cerebral cortex of rats.     

Neurotransmitter receptors in the developing cerebral cortex

This review deals with several aspects of neurotransmitter receptor development in the primate cerebral cortex. It describes the presence of multiple neurotransmitter receptors in the transient zones of the fetal cerebral wall. These zones are involved in the production and migration of cortical neurons and the establishment of appropriate innervation of the cortex. It also suggests functions that neurotransmitter receptors may perform in these embryonic zones. In addition, this review shows that a remarkable diversity of neurotransmitter receptors develops concurrently in disparate areas of the primate cerebral cortex and discusses the implications of this finding on our understanding of the general principles underlying development of the cerebral cortical circuitry. Finally, it speculates on factors that may be involved in regulation of neurotransmitter receptor development in the primate cerebral cortex.     

Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer

The prognosis for patients with the high-grade cerebral glioma glioblastoma multiforme is poor. The median survival for primary tumors is < 12 months, with most recurring at the site of the original tumor, indicating that a more aggressive local therapy is required to eradicate the unresectable "nests" of tumor cells invading into adjacent brain. Two adjuvant therapies with the potential to destroy these cells are porphyrin-sensitized photodynamic therapy (PDT) and boron-sensitized boron neutron capture therapy (BNCT). The ability of a boronated porphyrin, 2,4-(alpha, beta-dihydroxyethyl) deuteroporphyrin IX tetrakiscarborane carboxylate ester (BOPP), to act as a photosensitizing agent was investigated in vitro with the C6 rat glioma cell line and in vivo with C6 cells grown as an intracerebral tumor after implantation into Wistar rats. These studies determined the doses of BOPP and light required to achieve maximal cell kill in vitro and selective tumor kill in vivo. The data show that BOPP is more dose effective in vivo by a factor of 10 than the current clinically used photosensitizer hematoporphyrin derivative and suggest that BOPP may have potential as a dual PDT/BNCT sensitizer.     

Ultrasonographic characteristics of first-trimester gestations in recurrent spontaneous aborters

OBJECTIVE: To compile, for the first time, serial ultrasonographic findings during the first trimester of pregnancy in women with a history of primary recurrent spontaneous abortion so as to define the dynamics of early normal and abnormal gestations in this category of gravidas. STUDY DESIGN: Transvaginal ultrasonograms were obtained weekly from 5 to 12 weeks' gestational age in 40 women, 10 each of four groups: recurrent spontaneous aborters and primiparas (controls), with both successful and failed gestations. RESULTS: Embryonic heart motion was detected in 40-50% of successful pregnancies during the fifth week of gestation and in the balance by the sixth week, while heart motion was detected in no more than 50% of pregnancies that later failed. Of the failed pregnancies, all were evident by the eighth week of gestation, including those with previously documented viability. The gestational sac size and crown-rump length were smaller than expected in both failed groups, with the sac size difference evident as early as week 5 and the crown-rump length difference apparent by week 7. CONCLUSION: Appropriate timing of the initial ultrasonogram in recurrent aborters (i.e., 8 weeks' gestational age) can identify, by means of heart motion and gestational sac features, all pregnancies that will ultimately fail.