BACKGROUND Repeated alcohol exposure is known to increase subsequent ethanol consumption in mice. However, the underlying mechanisms have not been fully elucidated. One postulated mechanism involves epigenetic modifications, including histone modifications and DNA methylation of relevant genes such as NR2B or BDNF. METHODS To investigate the role of epigenetic mechanisms in the development of...

BACKGROUND Xanthine oxidase is a major source of superoxide in the vascular endothelium. Previous work in humans demonstrated improved conduit artery function following xanthine oxidase inhibition in patients with obstructive sleep apnea. OBJECTIVES To determine whether impairments in endothelium-dependent vasodilation produced by exposure to chronic intermittent hypoxia are prevented by in v...

The drug-parasite relationships for isoniazid and rifampicin have been investigated, using cultures of M. tuberculosis and infected guinea-pigs. It is remarkable that there appear to be two entirely different mechanisms involved in intermittent chemotherapy with isoniazid and rifampicin. With isoniazid, any escape from the influence of the drug leads to diminished efficacy. On the other hand, w...

Between 1970 and 1975, 108 patients who presented with advanced or recurrent Hodgkin's disease and were free of disease after six courses of chemotherapy with mustine, vinblastine, procarbazine, and prednisone (MVPP) were allocated at random to one of two regiments of maintenance treatment: either intermittent treatment with vinblastine and procarbazine or intermittent treatment with MVPP. Afte...

Glucocorticoids, secreted by the adrenals in response to stress, have profound effects on behavioural responsiveness to psychostimulant drugs. We have studied the critical time-window for the influence of corticosterone on behavioural sensitisation to cocaine in relation to i) the stage of behavioural sensitisation, and ii) the time of drug exposure. Previously, we have identified a mouse strai...

Angiogenesis is a hallmark of tumor development and metastasis and is now a validated target for cancer treatment. However, the survival benefits of antiangiogenic drugs have thus far been rather modest, stimulating interest in developing more effective ways to combine antiangiogenic drugs with established chemotherapies. This review discusses recent progress and emerging challenges in this fie...