To better define the role of the various prostanoid synthases in the adjuvant-induced arthritis (AIA) model, we have determined the temporal expression of the inducible PGE synthase (mPGES-1), mPGES-2, the cytosolic PGES (cPGES/p23), and prostacyclin synthase, and compared with that of cyclooxygenase-1 (COX-1) and COX-2. The profile of induction of mPGES-1 (50- to 80-fold) in the primary paw was similar to that of COX-2 by both RNA and protein analysis. Quantitative PCR analysis indicated that induction of mPGES-1 at day 15 was within 2-fold that of COX-2. Increased PGES activity was measurable in membrane preparations of inflamed paws, and the activity was inhibitable by MK-886 to ≥90% with a potency similar to that of recombinant rat mPGES-1 (IC50 = 2.4 μM). The RNA of the newly described mPGES-2 decreased by 2- to 3-fold in primary paws between days 1 and 15 postadjuvant. The cPGES/p23 and COX-1 were induced during AIA, but at much lower levels (2- to 6-fold) than mPGES-1, with the peak of cPGES/p23 expression occurring later than that of COX-2 and PGE2 production. Prostacyclin (measured as 6-keto-PGF1α) was transiently elevated on day 1, and prostacyclin synthase was down-regulated at the RNA level after day 3, suggesting a diminished role of prostacyclin during the maintenance of chronic inflammation in the rat AIA. These results show that mPGES-1 is up-regulated throughout the development of AIA and suggest that it plays a major role in the elevated production of PGE2 in this model.

Transient forebrain ischemia produced by four-vessel occlusion (4-VO) triggers the delayed death of CA1 neurons in the hippocampus, resulting in behavioral deficits of spatial learning performance. We demonstrate that CA1 neuronal loss induced by 4-VO (12 min) is preceded by a selective and marked elevation of catalytically active caspase-3 in these neurons, indicative of apoptosis. Virally mediated overexpression of the anti-apoptotic gene X chromosome-linked inhibitor of apoptosis protein (XIAP) prevented both the production of catalytically active caspase-3 and degeneration of CA1 neurons after transient forebrain ischemia. CA1 neurons protected in this manner appeared to function normally, as assessed by immunohistochemical detection of the neuronal activity marker nerve growth factor inducible-A and by spatial learning performance in the Morris water maze. These findings indicate that caspase-3 activation is a key event in ischemic neuronal death and that blockade of this event by XIAP overexpression permits CA1 neurons to survive and operate properly after an ischemic insult.

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Background and Purpose. Systematic reviews and meta-analyses often include an evaluation of the methodological quality of the individual studies that have been included, and are usually conducted by at least 2 individuals. The objective of this study was to assess the methodological quality and reliability of a series of randomized controlled trials (RCTs) of both pharmacological and nonpharmacological interventions by use of the 10-item Physiotherapy Evidence-Based Database (PEDro) Scale. Methods. Two abstractors independently reviewed 81 RCTs assessing a variety of interventions. The Cohen kappa statistic and the intraclass correlation coefficient (ICC) were used to assess agreement between abstractors. Results. The average total PEDro scores were 5.94 (SD=1.43) for all studies combined, 6.88 (SD=1.2) for pharmacological studies, and 5.29 (SD=1.26) for nonpharmacological studies. The median score for pharmacological studies was significantly higher than that for nonpharmacological studies (7 versus 5). Pair-wise kappa scores ranged from a low of .452 for concealed allocation among drug trials to perfect agreement (1.00) for randomization and reporting of results from between-group comparisons. The ICCs associated with the cumulative PEDro score were .91 (95% confidence interval [CI]=.83–.94) for all studies, .89 (95% CI=.78–.95) for pharmacological studies, and .91 (95% CI=.84–.952) for nonpharmacological studies. Discussion and Conclusion. The methodological quality for pharmacological interventions was significantly higher than that for nonpharmacological interventions. There was good agreement between raters at an individual item level and in total PEDro scores. A lack of reporting clarity, poor organization of the report, or the failure to include salient details contributed to less-than-perfect agreement between raters. [Foley NC, Bhogal SK, Teasell RW, et al. Estimates of quality and reliability with the Physiotherapy Evidence-Based Database Scale to assess the methodology of randomized controlled trials of pharmacological and nonpharmacological interventions.Phys Ther. 2006;86:817 – 824.]

Patients admitted to a specialized rehabilitation unit received an average of 37 min a day engaged in therapeutic activities with both occupational and physical therapists. Although this value did not reach the standard of one hour, total amount of OT time contributed significantly to gains in FIM points during hospital stay.