In humans, cytoskeletal dystrophin and muscle LIM protein (MLP) gene mutations can cause dilated cardiomyopathy, yet these mutations may have different effects in mice, owing to increased accumulation of other, compensatory cytoskeletal proteins. Consequently, we characterized left-ventricular (LV) morphology and function in vivo using high-resolution cine-magnetic resonance imaging (MRI) in 2- to 3-month old dystrophin-deficient (mdx) and MLP-null mice, and their respective controls. LV passive stiffness was assessed in isolated, perfused hearts, and cytoskeletal protein levels were determined using Western blot analyses. In mdx mouse hearts, LV-to-body weight ratio, cavity volume, ejection fraction, stroke volume, and cardiac output were normal. However, MLP-null mouse hearts had 1.2-fold higher LV-to-body weight ratios (P<0.01), 1.5-fold higher end-diastolic volumes (P<0.01), and decreased ejection fraction compared with controls (25% vs. 66%, respectively, P<0.01), indicating dilated cardiomyopathy and heart failure. In both models, isolated, perfused heart end-diastolic pressure-volume relationships and passive left-ventricular stiffness were normal. Hearts from both models accumulated desmin and beta-tubulin, mdx mouse hearts accumulated utrophin and MLP, and MLP-null mouse hearts accumulated dystrophin and syncoilin. Although the increase in MLP and utrophin in the mdx mouse heart was able to compensate for the loss of dystrophin, accumulation of desmin, syncoilin and dystrophin were unable to compensate for the loss of MLP, resulting in heart failure.

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Pentasa sachets 1 g unit dose offers the same release of mesalazine as Pentasa 500 mg tablets. Drug release occurs throughout the gastrointestinal tract from stomach to colon, with the advantage of fewer oral doses and ease of swallowing.

AimsWe investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. Methods Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg −1 day −1 or placebo for 2 weeks in a double-blind crossover study. FEV 1 and PD 20 histamine were measured before and 8 h after the first dose of treatment and 8, 32 and 56 h after the final dose. PD 20 AMP was measured before treatment and 9 h after the final dose.Results Six patients did not tolerate theophylline. In the other 12 subjects there were no differences between treatments in daily PEF, symptom scores, rescue bronchodilator use, PD 20 histamine or FEV 1 up to 8 h post treatment. Following withdrawal of theophylline there were significantly lower values for mean FEV 1 (mean difference 0.15 l, 95% CI 0.03, 026) and PD 20 AMP compared to placebo but no difference in other end points.Conclusions The small rebound deterioration in lung function following regular treatment with therapeutic doses of oral theophylline is consistent with the development of tolerance.

Phase changes in cyclohexane have been studied by MD simulation on the AMT DAP computer, using a zero-pressure technique to simulate clusters of 512 molecules. This work builds upon a previous study [1] in which we performed MD calculations on a smaller sample and found a phase intermediate between the experimentally determined low temperature crystalline structure (C2/c) and the high temperature plastic one (Fm3m). This new phase had not been observed experimentally in the bulk at ambient pressure [2]. We determined the intermediate structure to be rhombohedral with a space group of [Formula: see text]. A subsequent neutron diffraction study of cyclohexane at high pressures (< 5) kbar has permitted the identification of two orthorhombic phases [3] which occur for deuterated cyclohexane. In addition, for very small sample sizes another, as yet unidentified, phase has been observed at ambient pressure [4]: clear evidence that there are differences between the crystal structure in the bulk and in small clusters. We therefore decided to extend our earlier work in order to investigate the behaviour of the phase as a function of sample size. Using a larger sample we find behaviour much closer to that seen in the bulk material. The rhombohedral structure is still observed but over a very much reduced temperature range and the transition temperatures are closer to those seen experimentally. Although -we cannot identify the structure observed by Bosio and Dumas [4] with that simulated it is clear that there is an obvious parallel with the behaviour of the model. A further study of this system is underway.