New insights into the pharmacokinetics and pharmacodynamics of natalizumab treatment for patients with multiple sclerosis, obtained from clinical and in vitro studies.

BACKGROUND The monoclonal antibody natalizumab (NAT) inhibits the migration of lymphocytes throughout the blood-brain barrier by blocking very late antigen (VLA)-4 interactions, thereby reducing inflammatory central nervous system (CNS) activity in patients with multiple sclerosis (MS). We evaluated the effects of different NAT treatment regimens. METHODS We developed and optimised a NAT assay to measure free NAT, cell-bound NAT and VLA-4 expression levels in blood and cerebrospinal fluid (CSF) of patients using standard and prolonged treatment intervals and after the cessation of therapy. RESULTS In paired CSF and blood samples of NAT-treated MS patients, NAT concentrations in CSF were approximately 100-fold lower than those in serum. Cell-bound NAT and mean VLA-4 expression levels in CSF were comparable with those in blood. After the cessation of therapy, the kinetics of free NAT, cell-bound NAT and VLA-4 expression levels differed. Prolonged intervals greater than 4 weeks between infusions caused a gradual reduction of free and cell-bound NAT concentrations. Sera from patients with and without NAT-neutralising antibodies could be identified in a blinded assessment. The NAT-neutralising antibodies removed NAT from the cell surface in vivo and in vitro. Intercellular NAT exchange was detected in vitro. CONCLUSIONS Incorporating assays to measure free and cell-bound NAT into clinical practice can help to determine the optimal individual NAT dosing regimen for patients with MS.

Radiocarbon datings of mollusk shells, sedimentation rates and accumulation rates of sediment matter in core PS2718-6

A bottom sediment core about 8 m long sampled in the eastern Kara Sea near the entrance to the Vil'kitsky Strait was studied. An age model was constructed based on four 14C datings obtained from by thy accelerating mass spectrometry method. Results of grain size, chemical, mineralogical, and foraminiferal analyses were adjusted to the model. A paleoceanological interpretation of these data together with paleoclimatic data on the Bol'shevik Island located in the neighborhood was performed.

Interpretative analysis of surfical sediments as an aid in transport studies of dredged materials, Cape Canaveral, Florida /

"March 1984."

Introduction to the study of international law, designed as an aid in teaching and in historical studies;

Appendix II: List of the most important treaties since the reformation, with a brief statement of their provisions: p. [423]-501.

In-depth countermeasure report on selected countermeasures not covered separately in analytic studies. Annual report. 1973. Section II.

National Highway Traffic Safety Administration, Office of Alcohol Countermeasures, Washington, D.C.

First premarital cohabitation in the United States: 2006-2010 National Survey of Family Growth /

Mode of access: Internet.

The linear scanner in clinical studies /

"August 1960."

Close-in shock studies : final report /

"PNE-104F Nuclear Explosions-Peaceful Applications."

Close-in shock studies : preliminary report /

"U.S. Atomic Energy Commission Plowshare Program ; Project Gnome, Carlsbad, New Mexico, December 10, 1961"--Cover.

P. Chrysostomi Hanthaler ... Exercitationes faciles de numis veterum pro Tyronibus ... Pars 5. De votivis populi studiis in Augustos. Pars 6. & ultima. De consecrationis augustae impio delirio. Sequitur Appendix. De nonnullis coloniarum, & urbium graecarum numis

Mode of access: Internet.

Farmers in business, studies in cooperative enterprise.

Bibliography: p. 433-434. Bibliographical footnotes.