Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts

We performed a prospective, 12‐month, single‐center, nonrandomized, open‐label pilot study to investigate the use of belatacept therapy combined with alemtuzumab induction in renal allografts with preexisting pathology, as these kidneys may be more susceptible to additional toxicity when exposed to calcineurin inhibitors posttransplant. Nineteen belatacept recipients were matched retrospectively to a cohort of tacrolimus recipients on the basis of preimplantation pathology. The estimated glomerular filtration rate was not significantly different between belatacept and tacrolimus recipients at either 3 or 12 months posttransplant (59 vs 45, P = 0.1 and 56 vs 48 mL/min/1.72/m², P = 0.3). Biopsy‐proven acute rejection rates at 12 months were 26% in belatacept recipients and 16% in tacrolimus recipients (P = 0.7). Graft survival at 1 year was 89% in both groups. Alemtuzumab induction combined with either calcineurin inhibitor or costimulatory blockade therapies resulted in similar acceptable one‐year outcomes in kidneys with preexisting pathologic changes. Longer‐term follow‐up may be necessary to identify preferential strategies to improve outcomes of kidneys at a higher risk for poor function (ClinicalTrials.gov—NCT01496417).     

Vasorelaxing effect in rat thoracic aorta caused by laurotetanine isolated from Litsea cubeba Persoon

Abstract— The pharmacological effects of laurotetanine on rat isolated thoracic aorta were examined. The contraction of aortic rings caused by high potassium (60 Mm ) and cumulative concentrations of calcium (0?03–3 Mm ) was inhibited by 3–50 μm laurotetanine in a dose-dependent manner with an IC50 value of 19·8 ± 3·6 μm (n = 6) in a 1 Mm Ca²⁺ medium. The phenylephrine (3 μm )-induced contraction was also inhibited by laurotetanine. Its effect was more marked on the tonic contraction than on the phasic contraction and was not easily washed-out. On addition of laurotetanine during the tonic contraction, relaxation could also be observed. This relaxing effect was not antagonized by indomethacin (20 μm ) and was still seen in denuded aorta or in the presence of nifedipine (1 μm ). The caffeine (20 Mm )-induced contraction was not affected by laurotetanine. cAMP and cGMP levels of aorta were not changed by laurotetanine. It is concluded that laurotetanine relaxed the rat thoracic aorta mainly by suppressing the Ca²⁺ influx through both voltage- and receptor-operated calcium channels.     

Conformation of cyclosporin A in polar solvents

A major conformation of cyclosporin A in methanol and in aqueous methanol was revealed by some simple NMR experiments. Thus, a stepwise transition of cyclosporin A conformation from 100% CDCl₃ to 100% CD₃OD was followed by ¹H NMR, which showed that the chloroform conformation of cyclosporin A was still the major one in methanol. Employing the same technique, it was also shown that the chloroform conformation of cyclosporin A was one of the major conformations in 50% aqueous methanol. This may be the first experimental determination of a major conformation of cyclosporin A in polar solvents.     

Postural stability, tardive dyskinesia and developmental disability

ABSTRACT. The postural stability of four adult populations was examined through force platform methods. The four groups were classified as: (1) developmentally disabled (severely and profoundly mentally retarded) with tardive dyskinesia; (2) developmentally disabled but with no history of neuroleptic medication; (3) tardive dyskinetic but of normal intelligence; and (4) a normal and healthy control group. Postural conditions included standing still with arms at side, standing still with one arm or both arms parallel to the ground, and standing still while swinging both arms in the sagittal plane. The findings showed that both tardive dyskinetic and/or developmentally disabled groups exhibited greater sway and variability in centre of pressure motion in contrast to the control group. The developmental disabled with tardive dyskinesia group also exhibited a strong tendency to produce a different form to the postural sway strategy in that they produced rhythmical centre of pressure motions during stance that were, to some degree, task dependent. The findings show that the combined effects of developmental disability and tardive dyskinesia produce qualitatively and quantitatively different features in postural stability panems. The data suggest that postural stability measures may be a useful index to assess tardive dyskinesia.