Beta-proline analogues as agonists at the strychnine-sensitive glycine receptor.

3-Carboxy-3,4-dehydropyrrolidine was found to bind with affinity equal to that of glycine in a [3H]strychnine binding assay. Simple substitution of the 1-, 2-, 4-, or 5-position resulted in marked loss of affinity. A decline in affinity was also found upon enlargement, contraction, or saturation of the 5-membered ring. However, beta-proline and azetidine-3-carboxylic acid retained significant binding affinity. Despite its good affinity in [3H]strychnine binding, 3-carboxy-3,4-dehydropyrrolidine showed only weak agonist activity in intracellular recordings of cultured murine spinal cord neurons. This apparent lack of correlation between binding and functional results is discussed in light of the current models of the strychnine-sensitive glycine receptor.     

The active ingredient in EMDR: is it traditional exposure or dual focus of attention?

Very little is known about the mechanisms that underlie the therapeutic effectiveness of eye movement desensitization and reprocessing (EMDR). This study tested whether the content of participants' responses during EMDR is similar to that thought to be effective for traditional exposure treatments (reliving), or is more consistent with distancing, which would be expected given Shapiro's proposal of dual process of attention. The responses made by 44 participants with post‐traumatic stress disorder (PTSD) were examined during their first EMDR treatment session. An independent rater coded these responses according to whether they were consistent with reliving, distancing or focusing on material other than the primary trauma. The coding system was found to have satisfactory inter‐rater reliability. Greatest improvement on a measure of PTSD symptoms occurred when the participant processed the trauma in a more detached manner. Cross‐lagged panel correlations suggest that processing in a more detached manner was a consequence of the EMDR procedure rather than a measure that covaried with improvement. Copyright © 2006 John Wiley & Sons, Ltd.     

Issues in the cross-national assessment of health technology.

With the growing international literature in economic evaluation and the rapid spread of new health technologies, there is a need to undertake, or at least interpret, economic evaluations on the international level. However, the ways in which cross-national differences affect the cost-effectiveness of health technologies or their evaluations have never been studied. This paper explores these issues by taking advantage of a unique situation in which the same economic evaluation of a new indication for a health technology was conducted simultaneously in four countries using an identical methodology. The study showed that if prior agreement on methods can be reached and local data applied, economic evaluations can be undertaken in a way that facilitates the extrapolation of results from country to country.     

Nutrient signalling in the regulation of human muscle protein synthesis

The mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are important nutrient- and energy-sensing and signalling proteins in skeletal muscle. AMPK activation decreases muscle protein synthesis by inhibiting mTOR signalling to regulatory proteins associated with translation initiation and elongation. On the other hand, essential amino acids (leucine in particular) and insulin stimulate mTOR signalling and protein synthesis. We hypothesized that anabolic nutrients would be sensed by both AMPK and mTOR, resulting in an acute and potent stimulation of human skeletal muscle protein synthesis via enhanced translation initiation and elongation.
We measured muscle protein synthesis and mTOR-associated upstream and downstream signalling proteins in young male subjects ( n = 14) using stable isotopic and immunoblotting techniques. Following a first muscle biopsy, subjects in the 'Nutrition' group ingested a leucine-enriched essential amino acid–carbohydrate mixture (EAC). Subjects in the Control group did not consume nutrients. A second biopsy was obtained 1 h later. Ingestion of EAC significantly increased muscle protein synthesis, modestly reduced AMPK phosphorylation, and increased Akt/PKB (protein kinase B) and mTOR phosphorylation ( P < 0.05). mTOR signalling to its downstream effectors (S6 kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation status) was also increased ( P < 0.05). In addition, eukaryotic elongation factor 2 (eEF2) phosphorylation was significantly reduced ( P < 0.05). Protein synthesis and cell signalling (phosphorylation status) was unchanged in the control group ( P > 0.05).
We conclude that anabolic nutrients alter the phosphorylation status of both AMPK- and mTOR-associated signalling proteins in human muscle, in association with an increase in protein synthesis not only via enhanced translation initiation but also through signalling promoting translation elongation.     

Imagery Vividness Affects Habituation Rate

In order to investigate the effect of individual differences in imagery vividness on habituation rate, 14 subjects were threatened with receiving and then imagined receiving an electric shock. Subjects first habituated to a tone which was then used as an auditory signal for the shock threat and the imagined shock. The skin conductance response (SCR) was used to follow the course of habituation. Results demonstrated that subjects with non-vivid imagery habituated to the tone more rapidly than subjects with vivid imagery when the tone was associated with imagining an electric shock. Implications of this finding for therapeutic techniques using instructed imagery are discussed.     

Hemolytic uremic syndrome with hypocomplementemia, serum C3NeF, and glomerular deposits of C3

A 4-year-old boy had hemolytic uremic syndrome (HUS) associated with depression of serum C3 level, a B-hemolytic streptococcal throat infection, and an elevated level of antistreptolysin O titer. In addition to the characteristic histologic changes associated with this syndrome, substantial infiltration of polymorphonuclear leukocytes and nodular deposits of C3 globulin were seen in the glomeruli of the first biopsy specimen. Two months after clinical remission, he had a recurrence of hemolytic anemia, thrombocytopenia, and acute renal failure. The serum C3 concentration had decreased again, and serum C3NeF was detected in the serum. The typical changes associated with HUS were still present on electron microscopy. Bilateral nephrectomy and renal transplantation were done because of the development of uncontrollable severe hypertension and increasing azotemia. This patient had three manifestations of HUS, but because of several differences, such as hypocomplementemia, serum C3NeF, a recurrence, and persistent glomerular deposits of C3 globulin, he appears to have had a different form of the syndrome.