Modeling of acute spinal cord injury in the rat: neuroprotection and enhanced recovery with methylprednisolone, U-74006F and YM-14673

We used a new injury device that produces consistent spinal cord contusion injuries (T8) in rats to compare the behavioral and histologic effects of methylprednisolone sodium succinate (MPSS) administration, the clinical standard of therapy after acute spinal cord injury (ASCI), with the 21-aminosteroid, U-74006F (U74), and the TRH analogue, YM-14673 (YM), at different trauma doses. Three sequential experiments were conducted: Experiment 1. U74 (3.0/1.5/1.5 mg/kg; 10/5/5 mg/kg; 30/15/15 mg/kg), MPSS (30/15/15 mg/kg), or vehicle were administered intravenously (i.v.) at 5 min, 2 and 6 h after the injury (n = 8/group). U74 (10/5/5 mg/kg) and MPSS animals scored better than controls (Days 8-43) in open field walking (OFW); no other differences were seen between groups. Experiment 2. Dose-response evaluation of MPSS determined more effective doses. Groups (n = 16) receiving 30/30/30/30 mg/kg and 60/60/60/60 mg/kg i.v. at 5 min and 2, 4, and 6 h after the injury had better OFW scores than controls (Days 8-29; Day 29). Both groups performed better than controls (Days 8-29) on inclined plane (IP); 30 mg/kg animals scored higher on Day 29. Percentage tissue spared (%TS) at the lesion center was greater for 60 mg/kg animals (23.4%) than controls (17.3%). Experiment 3. Compounds were administered as in experiment 2 (n = 15/group); MPSS (60/30/30/30 mg/kg) and YM (1/1/1/1 mg/kg and 1 mg/kg/day ip) were most effective. YM and MPSS combination produced no additive effects. YM animals scored better than MPSS and control animals in OFW (Days 8-29) and better than controls on IP (Days 8-29; Day 29) and grid walking (Day 29). MPSS animals scored better than controls on IP (Days 8-29). YM and MPSS groups had greater %TS than controls. This series of experiments demonstrates the utility of this injury model and simple behavioral measures for preclinical assessment of pharmacologic agents. Under these experimental conditions, U74 demonstrated equivalent efficacy to MPSS, and YM demonstrated greater efficacy than MPSS in the treatment of ASCI.     

Why the Microsoft settlement won't work

The Microsoft antitrust trial, probably the most important technology-related legal case of our time, appears to be limping at last toward a conclusion. Unfortunately, there is an excellent chance that the software colossus will win, despite losing, without much to restrain it from going back to the heavy-handed, anticompetitive tactics that prompted the antitrust action in the first place.     

Why attend school? Chinese immigrant and European American preschoolers' views and outcomes.

The developing views of the purposes of school learning (PSLs) and related achievement among immigrant Chinese preschoolers and their European American (EA) age-mates were examined. Both culture and socioeconomic status (SES) were considered simultaneously, an often neglected research approach to studying Asian children. One hundred and fifty 4-year-olds—50 each of middle-class Chinese (CHM), low-income Chinese (CHL), and EA children—completed 2 story beginnings about school and were also tested for their language and math achievement. Results showed that 4-year-olds held sophisticated PSLs, ranging from intellectual to social and affect benefits. Large cultural and SES differences also emerged. CHM children mentioned more adult expectation and seriousness of learning than EA children who expressed more positive affect for self and compliance with adults. CHL children mentioned fewest PSLs. Achievement scores for oral expression of both immigrant groups were significantly lower than those of EA children despite similar reading and math achievement. Controlling for culture and SES, the authors found that children's articulated intellectual, but not other purposes, uniquely predicted their achievement in all tested domains. Cultural and SES influences on immigrant children are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Localization of authentic thromboxane A2/prostaglandin H2 receptor in the rat kidney

Using a polyclonal antibody against authentic thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptor protein, we assessed the distribution of this receptor in the normal rat kidney by routine methods of immunofluorescence microscopy. The receptor localized both in glomeruli and in tubules. In the former, the distribution of the receptor was most prominent along the lumen of glomerular capillary loops. Parietal epithelial cells of the Bowman's capsule, podocytes and mesangial cells also demonstrated immunostainable receptor. In the tubules, the receptor localized most prominently at the base of the brush border of proximal tubules and at the luminal surface of thick ascending limbs and distal convoluted tubules. These observations point to sites that are likely to be targeted by thromboxane A2 in forms of renal injury characterized by enhanced synthesis of this eicosanoid.     

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.     

Tracer monitored titrations: measurement of dissolved oxygen

The tracer monitored titration (TMT) technique is evaluated for measurement of dissolved oxygen. The TMT developed in this work uses a simple apparatus consisting of a low-precision pump for titrant delivery and an optical detector based on a white LED and two photodiodes with interference filters. It is shown that the classic Winkler method can be made free of routine volumetric and gravimetric measurements by application of TMT theory, which allows tracking the amounts of titrant and sample using a chemical tracer. The measurement precision of the prototype setup was 0.3% RSD.     

Electrochemical reduction of uridine in dimethyl sulfoxide: effect of the ribose group

The easier electrochemical reduction of uridine (1-β-D-ribofuranosyluracil) in dimethyl sulfoxide as compared to uracil (2, 4-dihydroxypyrimidine) by ca. 0.1 V is explicable on the basis of the electron-withdrawing effect of the ribose group. This effect and possible steric hindrance by the ribose group markedly affect the reaction sequence following the initial one-electron reduction to generate a radical anion, which abstracts a proton from the parent uridine (father—son reaction) to form the neutral uridine free radical and the uridine anion. With increasing uridine concentration, further reduction and protonation reactions are favored, resulting in an increase in the effective faradaic n from ca. 0.5 to 0.8. The availability of only one proton-donating site on uridine, ie, that on N(3), allows explication of the behavior of other hydroxypyrimidines such as uracil.     

A general equation and technique for the exact partitioning of chi-square contingency tables.

Considers the technique of the exact partitioning of chi-square contingency tables. Methods are presented for partitioning contingency tables into components. A general equation for chi-square is derived. The equation may be used for the calculation of exact values for (1) non-exhaustive sets of categories, and (2) situations in which some cells have small expected frequencies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)