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.     

Functional analysis of a rat sodium channel carrying a mutation for insect knock-down resistance (kdr) to pyrethroids

As a model for establishing an optimized medium for human in vitro fertilization (IVF), modified human tubal fluid (HTF) media containing amino acids at concentrations found in human serum and follicular fluid were prepared, and the effect of the media on development of random-bred (ICR) and F1 hybrid (CBF1) mice embryos was studied. The total concentrations of amino acids found in serum and follicular fluid were about one-third to one-half the concentrations present in two conventional media used in human IVF: Ham's F-10 and Eagle's minimal essential medium (MEM). When ICR mouse embryos were cultured in the HTF medium containing 21 amino acids at concentrations found in follicular fluid, the number of embryos developing to morulae at 72 h and to blastocysts at 96 h increased in comparison with those cultured in HTF medium. When HTF containing amino acids at concentrations found in serum was used, only induced morula formation at 72 h was enhanced. The number of hatching blastocysts at 96 h also increased when CBF1 mouse embryos were cultured with HTF supplemented with amino acids at concentrations found in follicular fluid. When ICR mouse embryos were cultured in modified HTF media containing concentrations of amino acids found in Ham's F-10 and MEM that contained higher concentrations of glutamine, embryo development was inhibited. The amount of ammonium produced during incubation for 3 days was significantly less when embryos were cultured in media containing concentrations of amino acids found in follicular fluid compared with when Ham's F-10 or MEM was the culture medium. Ammonium is produced by the breakdown of glutamine in the culture medium during incubation with or without embryos. These results suggest that the concentrations of amino acids found in follicular fluid are more effective and safer for embryo culture than those in other media currently in use.     

Capillary blood lactate concentrations during intermittent all-out exercise

Struma has called for treatment very early in medical history due to its appearance. At the beginning of our calendar, the physicians dealt with this problem already. This paper gives a historical review about the surgical treatment of struma.     

Chronic aluminum intoxication in rats: dose-dependent morphological changes

The objective of the study was to evaluate the chronic cytotoxic effect of very low nontoxic aluminum (Al) in the drinking water of rats. The control group (10 rats) received deionized water, whereas the two experimental groups (10 rats each) received Al in a dose of 5 mg and 20 mg/kg bw/day, respectively. Al was applied in their drinking water during the 6-month duration of the study. Light and electron microscopy (EM) was performed on several body tissues (i.e., kidney, liver muscle, brain). The results showed distinct dose-dependent changes in kidney and brain. In tubulo-interstitial part of the kidney many proximal tubules were hyperdilated. Their cells were swollen and the microvilli were largely lost. Atrophy of some tubules, surrounded by focal areas of interstitial fibrosis was also observed. Some of the glomeruli were undergoing partial sclerosis and in many focal mesangial hypercellularity was found. No distinct morphological changes in other peripheral tissues were observed. In brain, most pronounced changes were observed in hippocampus: they include spongioform changes in pyramidal layer, nuclear deformity and presence of vaculoes in the nuclei. Neurofibrillary degeneration, similar to neurofibrillary tangles in Alzheimer's disease, was also observed. It can thus be concluded that despite very low gastrointestinal absorption (less than 1%), Al in drinking water might accumulate in the long term in vital organs such as kidney and brain, with distinct cytotoxic and neurotoxic effects.     

Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats

Following spinal cord contusion in the rat, apoptosis has been observed in the white matter for long distances remote from the center of the lesion and is primarily associated with degenerating fiber tracts. We have previously reported that many of the apoptotic cells are oligodendrocytes. Here we show that the oligodendrocyte death is maximal at 8 days postinjury and suggest that loss of oligodendrocytes may result in demyelination of axons that have survived the initial trauma. There are two mechanisms that may account for the observed oligodendrocyte apoptosis. The apoptotic cell death may result from the loss of trophic support after axonal degeneration or it may be the consequence of microglial activation. The hypothesis that oligodendrocyte apoptosis is secondary to microglial activation is supported by our observations of microglia with an activated morphology in the same regions as apoptosis and apparent contact between some of the apoptotic oligodendrocytes and microglial processes. In addition to oligodendrocyte apoptosis, a subpopulation of microglia appears to be susceptible to apoptotic cell death as well, as evidenced by the presence of apoptotic bodies in OX42 immunopositive profiles. Thus, the population of apoptotic cells following spinal cord contusion is comprised of oligodendrocytes and putative phagocytic microglia or macrophages. Given the delayed time course of oligodendrocyte death, the apoptotic death of oligodendrocytes may be amenable to pharmacological intervention with subsequent improvement in functional recovery.     

Primary intraosseous meningioma of the vault

Primitive intra-osseous meningioma is a rare benign tumor. We report a case with a temporal localization and antro-attical extension into the petrous bone.