The efficacy of cyclosporin A, FK-506 and prednisolone to modify the adoptive transfer of experimental allergic encephalomyelitis (EAE).

The in vitro potency of the immunosuppressants Cyclosporin A (CsA), FK-506 and Prednisolone was assessed using the adoptive transfer model of EAE in the Lewis rat. Co-culture of encephalitogen-sensitised splenic leukocytes with Prednisolone did not inhibit the transfer of disease to naive histocompatible recipients despite significant suppression of neuroantigen-stimulated leukocyte proliferation by the drug. The addition of CsA (100 nM) to cultures inhibited the induction of adoptive EAE but a lower dose of the agent (10 nM) did not prevent the development of clinico-histopathological signs of disease. FK-506 (1 nM) was 100 times more effective than CsA at suppressing adoptive EAE thus emphasising the usefulness of the model in determining the relative efficacy of compounds to modify cell-dependent autoimmune disease.     

Effect of anti-interferon-γ and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse

SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-infeferonγ (IFN-γ) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-γ to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-γ. These findings support the notion that IL-2 is required for disease induction whereas IFN-γ plays a disease-limiting role early in the development of EAE.     

Saccadic trajectory in Huntington's disease.

Trajectories of saccadic eye movements can be modulated by the presence of a competing visual distractor. It is proposed that the superior colliculus (SC) controls the initial deviation through competitive lateral interactions. Given the ramifications of connections between basal ganglia (BG) thalamo-cortical circuitry and the SC, it was anticipated that this modulation would be differentially effected in those with Huntington's disease, which in its early stages is primarily a disorder of the BG. Horizontal deviation was determined for exogenously driven and endogenously driven vertical saccades in the presence of peripheral distractors. For neurologically healthy participants, the initial trajectories of both saccade types curved away from distractor locations, as predicted. However, for HD participants exogenous saccades consistently deviated leftwards, irrespective of distractor location. Endogenous saccades also revealed anomalous horizontal deviation, with significant leftward deviation evident for saccades directed upward and significant rightward deviation for saccades directed downward. Further, both groups generated a comparable proportion of erroneous responses to distractor stimuli, but only neurologically healthy participants demonstrated a response time advantage for compatible target/distractor presentation. These results suggest anomalous regulation of distractor-related activity in HD.     

Comparison of three oral sip-feed supplements in patients with cancer

This study set out to compare the long-term palatability of three oral sip-feed supplements. Sixty patients with various malignancies were randomized to receive one of three products—Build-Up, Fortimel and Fortisip. Participants were encouraged to take as much of the supplements each day for as long as they could manage. At the initial tasting, palatability and acceptability of the products was recorded and this was repeated throughout the trial period. Patients' reasons for discontinuing the trial were noted.
Build-Up was found to be the best-tolerated product of the three. It was taken for a significantly longer time than either Fortimel or Fortisip. There was an indication that Build-Up was more acceptable at the initial tasting than Fortisip but not Fortimel. A smaller proportion of patients stopped taking Build-Up due to flavour-related reasons compared to Fortisip but there was no significant difference between Build-Up and Fortimel. In all, 54% of the patients discontinued the trial for flavour-related reasons. Thirty-five per cent found that the sip-feeds they had been allotted unpalatable at the initial tasting, while 19% stopped the trial due to 'flavour fatigue'. Only 10% of the sample continued taking their allotted product for 90 days or more.