Cyclosporine Interacts with Mycophenolic Acid by Inhibiting the Multidrug Resistance-Associated Protein 2

In mycophenolate mofetil (MMF)-treated organ transplant recipients, lower mycophenolic acid (MPA) plasma concentrations have been found in cyclosporine (CsA) compared with tacrolimus (Tac)-based immunosuppressive regimens. We previously demonstrated that CsA decreases exposure to MPA and increases exposure to its metabolite MPA-glucuronide (MPAG), possibly by interfering with the biliary excretion of MPAG. To elucidate the role of the multidrug resistance-associated protein (Mrp)-2 in the interaction between MMF and CsA, we treated three groups of 10 Mrp2-deficient rats (TR- rat) for 6 days with either vehicle, CsA (8 mg/kg) or Tac (4 mg/kg) by oral gavage. Hereafter, co-administration with MMF (20 mg/kg) was started in all groups and continued through day 14. The 24-h MPA/MPAG area under the concentration-time curve (AUC) was determined after single (day 7) and multiple MMF doses (day 14). On both study days, there were no significant differences in the mean MPA and MPAG AUC between CsA and Tac-treated animals. We conclude that the pharmacokinetics of MMF are comparable in Mrp2-deficient rats receiving either CsA or Tac as co-medication. This finding suggests that CsA-mediated inhibition of the biliary excretion of MPAG by the Mrp2 transporter is the mechanism responsible for the interaction between CsA and MMF.     

Primary spinal epidural non-Hodgkin's lymphoma. The contribution of nuclear magnetic resonance imaging, therapeutic approach and review of the literature.

Primary spinal epidural lymphoma (Stage I) is diagnosed predominantly late after a long prodromal phase of local back pain resulting in spinal cord compression. The use of CT and NMR images in the early stage of investigation and their analysis may help to diagnose these cases prior to the appearance of neurologic deficit. We report on 2 patients who presented with prolonged localized back pain with sudden symptoms of spinal cord compression. CAT scan and NMR imaging demonstrated the characteristic appearance of lymphoma. Decompressive laminectomy supported the diagnosis. Radiotherapy treatment to the region of the non-Hodgkin's lymphoma resulted in complete resolution. Thereafter, systemic chemotherapy with CHOP achieved a good response.     

Glutathione effects on vitamin D metabolism in control and streptozotocin diabetic rat

The circulating concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)₂D₃] is a physiologic index of enzymatic activity of the renal 1-hydroxylase of 25-hydroxychole-calciferol (25-OH-D₃). Hydroxylation of 25-OH-D₃ and circulating 1,25-(OH)₂D₃ are decreased in the streptozotocin diabetic rat. We previously found that activity of another redox enzyme system, cytosolic superoxide dismutase, also decreased in streptozotocin diabetes, can be restored by treatment with glutathione. In the present experiment we tested the effect of glutathione treatment on vitamin D metabolism in control and diabetic rats. Enteral glutathione increased circulating 1,25-(OH)₂D₃ and decreased 25-OH-D₃ in both control and diabetic animals. These results suggest that exogenous glutathione increases 25-OH-D₃ 1-hydroxylation both under basal conditions in the normal animal and in diabetes-induced depression.     

Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Benchmarking in national health service procurement in Scotland.

The paper reports the results of a study on benchmarking activities undertaken by the procurement organization within the National Health Service (NHS) in Scotland, namely National Procurement (previously Scottish Healthcare Supplies Contracts Branch). NHS performance is of course politically important, and benchmarking is increasingly seen as a means to improve performance, so the study was carried out to determine if the current benchmarking approaches could be enhanced. A review of the benchmarking activities used by the private sector, local government and NHS organizations was carried out to establish a framework of the motivations, benefits, problems and costs associated with benchmarking. This framework was used to carry out the research through case studies and a questionnaire survey of NHS procurement organizations both in Scotland and other parts of the UK. Nine of the 16 Scottish Health Boards surveyed reported carrying out benchmarking during the last three years. The findings of the research were that there were similarities in approaches between local government and NHS Scotland Health, but differences between NHS Scotland and other UK NHS procurement organizations. Benefits were seen as significant and it was recommended that National Procurement should pursue the formation of a benchmarking group with members drawn from NHS Scotland and external benchmarking bodies to establish measures to be used in benchmarking across the whole of NHS Scotland.     

Reducing the risk of eating disorders in athletics

Athletes comprise a unique population with special needs for the management and treatment of eating disorders. Prevention of these disorders also requires special approaches and strategies. Common attitudes, beliefs, and practices in athletics believed to be related to pressures to diet or to engage in pathogenic weight loss methods are discussed. Strategies for educating athletes and sport management personnel regarding issues related to eating disorders are proposed. Additionally, changes in the athletic environment designed to reduce the risk of eating disorders developing are recommended.     

Long-term biocompatibility of implanted polymer-based intrafascicular electrodes

Polymer-based longitudinal intrafascicular electrodes (polyLIFEs) were chronically implanted into the sciatic nerve of white New Zealand rabbits (n=8) for a period of 6 months (hereafter referred to as the long-term group). The impact of the implantation procedure, as observed 6 months post surgery, was evaluated in a sham-treated control group (n=9). The contralateral sciatic nerve served as the control for each animal. Nerve-fiber counts, fiber diameters, and myelin thickness were estimated at the level of the implant site, 1.5 cm proximally, and 1.5 cm distally for both nerves in sham-treated and long-term groups. Implantation of polyLIFEs had no significant effect on fiber counts, nerve-fiber diameter, or myelin thickness. A slight increase in connective tissue in the vicinity of the implant site was evident in the long-term group, including a thin but dense capsule immediately surrounding the implanted electrode.