Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and "depressed" mice exposed to chronic mild stress.

During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice.

Salmonella Thompson associated with improper handling of roast beef at a restaurant in Sioux Falls, South Dakota.

In October 1996, we investigated an outbreak of Salmonella serotype Thompson infections associated with Restaurant A in Sioux Falls, South Dakota, and conducted two cohort studies among persons who ate at luncheons catered by Restaurant A. Fifty-two Salmonella Thompson infections were identified between 29 September and 14 October 1996. Infections occurred among employees and patrons at Restaurant A and among attendees at three luncheons catered by the restaurant on 7 October. Roast beef cooked at Restaurant A was the only food item significantly associated with illness. Cooking times and storage temperatures for roast beef were inadequate to prevent multiplication of Salmonella, and the chefs were unaware of proper cooking and storage temperatures. We conclude that improper handling of roast beef probably caused this outbreak of Salmonella Thompson infections. Better knowledge of food safety practices by the cooking staff at Restaurant A, through required food safety education, might have prevented the outbreak.

Arrangement of the disulphide bridges in human low-Mr kininogen.

The arrangement of the disulphide bridges in human low-Mr kininogen has been elucidated. Low-Mr kininogen contains 18 half-cystine residues forming nine disulphide bridges. The first and the last half-cystine residues of the amino acid sequence form a disulphide loop which spans the heavy- and the light-chain portion of the kininogen molecule. The other 16 half-cystine residues are linked consecutively to form eight loops of 4-20 amino acids; these loops are lined up in the heavy-chain portion of the kininogen molecule. In this way, a particular pattern of disulphide loops is formed which seems to be of critical importance for the inhibitor function of human kininogen.