We evaluated the prediction that postural instability would precede the subjective symptoms of motion sickness in a fixed-base flight simulator. Participants sat in a cockpit in a video projection dome and were exposed to optical flow that oscillated in the roll axis with exposure durations typical of flight simulation. The frequencies of oscillation were those that characterize spontaneous postural sway during stance. Head motion was measured prior to and during exposure to imposed optical flow. Of 14 participants, 6 were classified as motion sick, either during or after exposure to the optical oscillation. Prior to the onset of subjective symptoms, head motion among participants who later became sick was significantly greater than among participants who did not become motion sick. We argue that the results support the postural instability theory of motion sickness. Actual or potential applications include the prevention or mitigation of motion sickness in virtual environments.

OBJECTIVEOlanzapine (OLZ) is an atypical antipsychotic whose clinical efficacy is hampered by side effects including weight gain and diabetes. Recent evidence shows that OLZ alters insulin sensitivity independent of changes in body weight and composition. The present study addresses whether OLZ-induced insulin resistance is driven by its central actions.RESEARCH DESIGN AND METHODSSprague-Dawley rats received an intravenous (OLZ-IV group) or intracerebroventricular (OLZ-ICV group) infusion of OLZ or vehicle. Glucose kinetics were assessed before (basal period) and during euglycemic-hyperinsulinemic clamp studies.RESULTSOLZ-IV caused a transient increase in glycemia and a higher rate of glucose appearance (Ra) in the basal period. During the hyperinsulinemic clamp, the glucose infusion rate (GIR) required to maintain euglycemia and the rate of glucose utilization (Rd) were decreased in OLZ-IV, whereas endogenous glucose production (EGP) rate was increased compared with vehicle-IV. Consistent with an elevation in EGP, the OLZ-IV group had higher hepatic mRNA levels for the enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. Phosphorylation of hypothalamic AMP-activated protein kinase (AMPK) was increased in OLZ-IV rats compared with controls. Similarly, an intracerebroventricular infusion of OLZ resulted in a transient increase in glycemia as well as a higher Ra in the basal period. During the hyperinsulinemic period, OLZ-ICV caused a decreased GIR, an increased EGP, but no change in Rd. Furthermore, OLZ-ICV rats had increased hepatic gluconeogenic enzymes and elevated hypothalamic neuropeptide-Y and agouti-related protein mRNA levels.CONCLUSIONSAcute central nervous system exposure to OLZ induces hypothalamic AMPK and hepatic insulin resistance, pointing to a hypothalamic site of action for the metabolic dysregulation of atypical antipsychotics.

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Objective. To visualize early experimental arthritis with near-infrared fluorescence (NIRF) imaging in a murine model of antigen-induced arthritis (AIA).Methods. The target of NIRF was the F4/80 antigen present on the surface of macrophages infiltrating the inflamed synovial membrane. Imaging was performed using anti-F4/80 monoclonal antibodies (mAb) labeled with Cy5.5 fluorochrome. On day 7 of AIA, 6 mice received an intravenous (IV) injection of labeled mAb; control AIA mice (n ‫؍‬ 6) received an IV injection of Cy5.5-labeled isotype control antibody. NIRF imaging was performed before injection (baseline) and until 72 hours thereafter. Histologic evaluation of arthritis severity and immunohistochemical assessment of F4/80 antigen density were also performed on day 7.Results. NIRF imaging showed an accumulation of fluorochrome probes in the inflamed knee joints and, to a lesser extent, in the contralateral (nonarthritic) knee joints. The signal induced by mAb F4/80 was clearly higher than that generated by the isotype control. Accumulation of fluorochrome probes in the joints was confirmed histologically by confocal laser scanning microscopy.Conclusion. The use of fluorochromes allows imaging of arthritis in the near-infrared range. Accumulation in the contralateral, nonarthritic knee joints can be explained by the presence of sentinel macrophages in normal synovium or by a mild contralateral response due to systemic activation or neurogenic mechanisms.