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The staircase test consists of placing a naive mouse in an enclosed staircase with five steps and observing the number of steps climbed and rearings made in a 3-min period. All the clinically active anxiolytics tested (chlordiazepoxide, clorazepate, diazepam, lorazepam, meprobamate, phenobarbital) reduce rearing at doses which did not reduce the number of(More)
Benzodiazepines are widely used anxiolytics and anticonvulsants, and their potent sedative properties are routinely used in presurgical anaesthesia. However, they are also known to induce a strong anterograde amnesia in patients. Specific benzodiazepine antagonists have recently been described, some of which have intrinsic pharmacological properties that(More)
Endogenous tyrosine concentrations varied two-fold among various rat brain regions, tending to be highest in brain stem structures. Administration of L-tyrosine (100 mg/kg) increased tyrosine concentrations in all brain areas; high relative increases were observed in areas with low initial tyrosine concentrations and vice versa, resulting in a more uniform(More)
Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to(More)
In the 1,4-benzodiazepine (BZD) series the nature of the C(5) substituent is critical for activity. In tetrazepam this substituent is a cyclohexenyl ring, in all other clinically effective 1,4-BZD derivatives it is a phenyl ring. The activities of tetrazepam and diazepam, whose chemical structures differ only by the nature of the C(5) substituent, were(More)
Understanding the factors that impede immune responses to persistent viruses is essential in designing therapies for HIV infection. Mice infected with LCMV clone-13 have persistent high-level viremia and a dysfunctional immune response. Interleukin-7, a cytokine that is critical for immune development and homeostasis, was used here to promote immunity(More)
The effect of valproic acid and 10 close analogues (7 branched and 3 non-branched) were studied on the content of gamma-aminobutyric acid (GABA) in brain and on seizures induced by pentylenetetrazol (PTZ) in mice. All 8 branched fatty acids protected against seizures induced by pentylenetetrazol, but the 3 non-branched acids were inactive. A significant(More)
Identifying key factors that enhance immune responses is crucial for manipulating immunity to tumors. We show that after a vaccine-induced immune response, adjuvant interleukin-7 (IL-7) improves antitumor responses and survival in an animal model. The improved immune response is associated with increased IL-6 production and augmented T helper type 17 cell(More)
BACKGROUND The immune deficiency of human immunodeficiency virus (HIV) infection is not fully corrected with ARV therapy. Interleukin-7 (IL-7) can boost CD4 T-cell counts, but optimal dosing and mechanisms of cellular increases need to be defined. METHODS We performed a randomized placebo-controlled dose escalation (10, 20 and 30 µg/kg) trial of 3 weekly(More)
The quinolines PK 8165 and PK 9084 bind to brain benzodiazepine receptors in vitro. However, unlike diazepam, these molecules do not reduce GABA turnover, possess anxiolytic properties, or displace [3H]flunitrazepam from benzodiazepine receptors in vivo. The pharmacological properties of PK 8165 and PK 9084 in vivo are thus unrelated to the benzodiazepine(More)