Cutting edge: Natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis

The humanized anti-alpha(4) integrin Ab Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis. Natalizumab is thought to exert its therapeutic efficacy by blocking the alpha(4) integrin-mediated binding of circulating immune cells to the blood-brain barrier (BBB). As alpha(4) integrins control other immunological processes, natalizumab may, however, execute its beneficial effects elsewhere. By means of intravital microscopy we demonstrate that natalizumab specifically inhibits the firm adhesion but not the rolling or capture of human T cells on the inflamed BBB in mice with acute experimental autoimmune encephalomyelitis (EAE). The efficiency of natalizumab to block T cell adhesion to the inflamed BBB was found to be more effective in EAE than in acute systemic TNF-alpha-induced inflammation. Our data demonstrate that alpha(4) integrin-mediated adhesion of human T cells to the inflamed BBB during EAE is efficiently blocked by natalizumab and thus provide the first direct in vivo proof of concept of this therapy in multiple sclerosis.

Effect of animal species and age on plate-induced vascular damage in cortical bone

Plates used for fracture fixation produce vascular injury to the underlying cortical bone. During the recovery of the blood supply, temporary osteoporosis is observed as a result of Haversian remodeling of the necrotic bone. This process temporarily reduces the strength of the bone. We tackled the postulate that quantitative differences exist between animal species, and in different bones within the same species, due to variations in the relative importance of the endosteal and periosteal blood supplies. Using implants scaled to the size of the bone, we found comparable cortical vascular damage in the sheep and in the dog, and in the tibia and femur of each animal. We observed a significant reduction in cortical vascular damage using plates that had a smaller contact area with the underlying bone. No significant difference in cortical vascular damage was noted in animals of different ages.

[Mass culling in the context of animal disease outbreaks--veterinarians caught between ethical issues and control policies]

In recent years controversial discussions arose during major animal disease outbreaks in the EU about the ethical soundness of mass culling. In contrast to numerous publications about ethical issues and laboratory animals/animal experiments, literature concerning ethical deliberations in the case of mass culling as a means of outbreak control remain scarce. Veterinarians in charge of decision about and implementation of mass culling actions find themselves in an area of conflict in between the officially required animal disease control policy and a public that is increasingly critical. Those veterinarians are faced with the challenge to defend the relevant decisions against all stakeholders and also themselves. In this context an interdisciplinary workshop was initiated in Switzerland in October 2007 with ethicians and (official) veterinarians from Germany, Switzerland and Austria. With the aim to identify ethical components of animal disease control for official veterinarians, talks and moderated group discussions took place. This article summarizes selected discussion points and conclusions.

Identification of animal Pasteurellaceae by MALDI-TOF mass spectrometry

Species of the family Pasteurellaceae play an important role as primary or opportunistic animal pathogens. In veterinary diagnostic laboratories identification of this group of bacteria is mainly done by phenotypic assays while genetic identification based on housekeeping genes is mostly used for research and particularly important diagnostic samples. MALDI-TOF MS seems to represent a promising alternative to the currently practiced cumbersome, phenotypic diagnostics carried out in many veterinary diagnostic laboratories. We therefore assessed its application for animal associated members of the family Pasteurellaceae. The Bruker Biotyper 3.0 database was complemented with reference spectra of clinically relevant as well as commensal animal Pasteurellaceae species using generally five strains per species or subspecies and tested for its diagnostic potential with additional, well characterized field isolates. About 250 strains comprising 15 genera and more than 40 species and subspecies were included in the study, covering most representatives of the family. A high discrimination at the genus and species level was observed. Problematic discrimination was only observed with some closely related species and subspecies. MALDI-TOF MS was shown to represent a highly potent method for the diagnosis of this group of animal pathogens, combining speed, precision and low running costs.