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Objective: To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Methods: 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48. Results: At week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation. Conclusion: Treatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified.

The mercury concentration in 70 breast milk samples (Hg-M) from 46 mothers, collected within the first 7 days after delivery, was determined by cold vapour atomic absorption spectrometry. For comparison, 9 formula milk samples (reconstituted with Hg-free water) were investigated. The Hg-M in the human milk samples ranged from0.2 to 6.86 micrograms/L (median 0.37), in the formula milk samples from 0.4 to 2.5 micrograms/L (median 0.76). The Hg-M in the breast milk samples correlates positively with the number of maternal teeth with dental amalgam. The mean Hg-M of amalgam-free mothers was0.2 microgram/L, while milk from mothers with 1-4 amalgam fillings contained 0.57 microgram/L, with 5-7 fillings 0.50 microgram/L and with more than 7 fillings 2.11 micrograms/L. Hg-M correlated negatively to the day after delivery. Frequency of fish consumption tends to influence Hg-M positively, while the age of the mother shows no significant correlation. In the first 2 to 3 days after delivery some colostrum samples with Hg-M higher than in formula milk were found. Later on, the Hg-concentration in the breast milk was equal or even lower to that in formula milk. The higher Hg burden of infants' tissues from mothers with dental amalgam, as reported previously, must be explained (1) by a prenatal transfer of Hg from the mother's fillings through the placenta to the fetus, followed by a redistribution of this Hg in the body of the newborn, and (2) an additional burden via breast milk. Nevertheless, the comparison of Hg-M in breast and formula milk, the relatively moderate Hg burden in both kinds of milk, and the multiple manifest advantages of breast feeding speak against any limitation of nursing, even for mothers with a large number of dental amalgam fillings.

The aggregation of proteins into oligomers and amyloid fibrils is characteristic of several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process of aggregation of a-synuclein (a-syn) from monomers, via oligomeric intermediates, into amyloid fibrils is considered the disease-causative toxic mechanism. We developed a-syn mutants that promote oligomer or fibril formation and tested the toxicity of these mutants by using a rat lentivirus system to investigate loss of dopaminergic neurons in the substantia nigra. The most severe dopaminergic loss in the substantia nigra is observed in animals with the a-syn variants that form oligomers (i.e., E57K and E35K), whereas the a-syn variants that form fibrils very quickly are less toxic. We show that a-syn oligomers are toxic in vivo and that a-syn oligomers might interact with and potentially disrupt membranes.

Fazit: Die gegenüber früheren Untersuchungen gestiegenen Bestandsgrößen weisen darauf hin, daß sich im ökologischen Landbau ein ähnlicher Strukturwandel wie in der konventionellen Landwirtschaft vollzieht (Wachstum und Spezialisierung). Die Auswertung zeigt ferner, daß die Betriebe zunehmend bemüht sind, bereits jetzt den zukünftigen Haltungsvorschriften der EU-Verordnung zu entsprechen. Fast alle Betriebe führen Weidegang durch und trotz der relativ geringen Bestandsgröße haben die meisten Betriebe bereits Laufställe; Auslaufmöglichkeiten fallen demgegenüber allerdings noch ab.