Six Weeks of Voluntary Exercise don’t Protect C57BL/6 Mice Against Neurotoxicity of MPTP and MPP+

Exercise improves the central nervous system (CNS) functions and is widely recommended for neurological patients with, e.g., Alzheimer’s and Parkinson’s disease (PD). However, exercise-induced neuroprotection is an open discussion. Here, the intranasal administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 65 mg/kg) caused death of dopaminergic neurons in the substantia nigra pars compacta and depletion of dopamine in the striatum of C57BL/6 mice. 1-Methyl-4-phenylpyridinium, the active metabolite of MPTP, also inhibited complex-I activity of mitochondria isolated from the CNS of mice. However, 6 weeks of exercise on voluntary running wheels did not protect against nigrostriatal neurodegeneration or mitochondrial inhibition, suggesting that benefits of exercise for PD may not be associated with neuroprotection. The literature presents other candidates, such as neurotrophins or increased antioxidant defenses.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

Structure-activity relationships leading to WAY-121,520, a tris aryl-type,indomethacin-based,phospholipase A2 (PLA2)/leukotriene biosynthesis inhibitor

We were intrigued by reports of the inhibition of phospholipase A₂ (PLA₂) by indomethacin. In order to increase the potency of the indomethacin system as an inhibitor of PLA₂, it was decided to make more lipophilic analogs. Indeed, covalent attachment of a quinoline ring to the methoxy substituent of indomethacin affords WAY-122,220 which is almost an order of magnitude more potent than indomethacin in inhibiting human synovial fluid PLA₂ (IC₅₀=15 and 145 μM, respectively). TheN−p-chloro-benzyl analog of this compound, WAY-121,520, was an even more potent inhibitor of PLA₂ (IC₅₀=4 μM). Structural analyses and molecular modeling suggest that these compounds may inhibit PLA₂ by mimicking arachidonic acid. WAY-121,520 is also a potent leukotriene biosynthesis inhibitor both in the rat PMN and mouse macrophage assays (IC₅₀=10 and 4 nM, respectively), possibly acting via a 5-LO (5-lipoxygenase) translocation inhibition mechanism. The multiple actions of WAY-121,520 may contribute to its favorable anti-inflammatory profile.

     

Zur Frage der Humoralen Faktoren-Koppelungen Bei ÜberlÜftungsversuchen unter Besonderer BerÜcksichtigung von Epileptikern

Ohne Zusammenfassung     

Vegetatives Nervensystem,HypercholesterinÄmie und Arteriosklerose in ihren Beziehungen zu Einander

Zusammenfassung Bei geeigneten Personen gelingt es, durch Sympathicuserregung (Adrenalininjektionen) HypercholesterinÄmien zu erzeugen. Da die Entstehung der menschlichen Arteriosklerose mit einer Cholesterinstoffwechselstörung zusammenhÄngt und neben anderen Komponenten bei der Ätiologie dieser GefÄ\erkrankungen seelische Erregungen eine Rolle spielen, weisen unsere Untersuchungsresultate darauf hin, da\ Beziehungen bestehen zwischen ErregungszustÄnden im vegetativen Nervensystem, HypercholesterinÄmie und Arteriosklerose.