Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3-1,6 beta glucan pathogen associated molecular pattern, in healthy volunteer subjects.

BACKGROUND: BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported. SUBJECTS AND METHODS: In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (i.v.) infusion of BTH1677 at 0.5, 1, 2, 4, or 6 mg/kg or placebo, respectively. In the Phase 1b multi-dosing study, subjects were randomized (3:1 per cohort) to 7 daily i.v. infusions of BTH1677 at 1, 2, or 4 mg/kg or placebo, respectively. Safety and PK non-compartmental analyses were performed. RESULTS: Thirty-six subjects (N = 24 Phase 1a; N = 12 Phase 1b) were randomized to treatment. No deaths or serious adverse events occurred in either study. Mild or moderate adverse events (AEs) occurred in 67% of BTH1677-treated subjects in both studies. Treatment-related AEs (occurring in ≥10% of subjects) included dyspnea, flushing, headache, nausea, paraesthesia, and rash in Phase 1a and conjunctivitis and headache in Phase 1b. BTH1677 serum concentration was linear with dose. Clearance, serum elimination half-life (t1/2) and volume of distribution (Vss) were BTH1677 dose-independent. In Phase 1b, area under the curve, t1/2, and Vss values were larger at steady state on days 6-30 versus day 0. CONCLUSIONS: BTH1677 was well tolerated after single doses up to 6 mg/kg and after 7 daily doses up to 4 mg/kg.

Determination by HPLC of adrenalin (E) and of noradrenalin (NE) in certain species of mesopelagic fish in the Strait of Messina.

The presence of adrenalin (E) and noradrenalin (NE) was found by HPLC both in the photophores and at other tissue levels of numerous species of mesopelagic fish in The Strait of Messina, with the aim of determining the incidence of these catecholamines in photophores, in light transmission and the eventual presence at other tissue levels.

[Bencyclane in memory disorders. Treatment of memory disorders caused by electroshock in a group of depressed patients]. / Il bencyclan nelle turbe della funzione mnestica. Trattamento delle dismnesie da elettroshock in un gruppo di pazienti depressi.

Subjects treated with electroshock and subjected simultaneously to bencyclan at a dose of 00 mg (2 ampoules) i.v. and 100 mg (1 pill) per os pro die did not present dysmnesia either during the intervals between one electroshock treatment and another, nor at the conclusion of treatment (on average 12 sessions in about 40 days), while a control group treated at the same rhythm and with the same number of sessions, but without bencyclan, presented considerable memory lapses which disappeared only after a lengthy period of this latter treatment. Memory disturbances have been evaluated with a memorization test to which all patients were subjected. This test belongs to the group of intellectual efficiency reactive tests used in the psychology laboratory of the Catholic University of Milan; it consists of a group of 12 figures of common objects which, once observed, have to be recalled exactly immediately and some time later by the patient, who has to indicate the name and position of the objects represented in the chart.