Sally Elizabeth Adams

Agomelatine facilitates positive versus negative affective processing in healthy volunteer models.

Agomelatine is a new antidepressant with a novel profile of pharmacological action. The clinical efficacy of agomelatine has been established in major depression, but its actions on emotional bias are unknown. Consequently, the current experimental study assessed the effect of agomelatine on emotional processing in healthy volunteers using an Emotional Test Battery shown to be sensitive to serotonin and noradrenaline reuptake inhibitors. Volunteers were randomized to receive placebo, 25 mg or 50 mg of agomelatine over a 7-day period in a double-blind parallel groups design. Emotional processing (n = 48) was assessed on the morning of day 8 using the Emotional Test Battery which included facial expression recognition, emotional memory, attentional visual probe and emotion-potentiated startle. Mood and subjective state were monitored before and during treatment. Agomelatine (25 mg) decreased subjective ratings of sadness, reduced recognition of sad facial expressions, improved positive affective memory and reduced the emotion-potentiated startle response. The results show that agomelatine has more selective effects on the processing of social facial cues than conventional antidepressants, which could contribute to less blunting of emotional experience. The study highlights the potential value of volunteer models in drug development for screening and profiling of novel antidepressants.

Matrix metalloproteinases in neuro-inflammatory disease

The matrix metalloproteinases (MMPs) are produced by many cell types including activated leucocytes and connective tissue cells in a wide range of inflammatory, infectious and traumatic disorders [1]. The presence of active MMPs in local excess over the levels of their natural inhibitors, the TIMPs, is thought to mediate pathology in many of these conditions, such as rheumatoid arthritis, inflammatory bowel disease and cancer [2]. It is only in the last few years that the inflammatory nature of many diseases of the nervous system has been recognised [3, 4]. This chapter reviews the available evidence to show that MMPs are produced within the nervous system in several important diseases, notably multiple sclerosis, Guillain-Barre syndrome and stroke, and that inhibiting their activity may be of clinical benefit.

Proliferative Responses to the V3 Region of HIV Envelope Are Enhanced Following Immunization with V3:Ty Virus-Like Particles in Mice

T helper(Th)-lymphocytes play a vital role in the immune response to an invading organism. The activation of CD4-positive Th lymphocytes in the production of cytokines which enhance the function of cytotoxic T-lymphocytes (CTL), promote differentiation of B-lymphocytes into antibody-producing plasma cells, and increase the frequency of memory B-lymphocytes. It is likely that both of these arms of the immune response will be involved in protection against the human immunodeficiency virus (HIV). A strong anti-HIV CD8-positive activity is associated with increased long term survival (1). Neutralizing antibodies directed against the HIV envelope have been described and evidence presented which suggests a key protective role for these antibodies (2,3). An HIV vaccine will, therefore, need to include epitopes recognized by Th lymphocytes.