The effect of C-terminal amidation on the antimicrobial and hemolytic activities of antimicrobial peptides was studied using three cationic peptides which form amphiphilic α-helices when bound to membranes. The natural antimicrobial peptide PGLa, the designermade antibiotic MSI-103, and the cell-penetrating “model amphipathic peptide” (MAP) are all amidated in their original forms, and their bi...

Generic immunosuppressive drugs are available in Europe, Canada, and the United States. Between countries, there are large differences in the market penetration of generic drugs in general, and for immunosuppressive drugs in particular. The registration criteria for generic immunosuppressive drugs are often criticized. However, it is unlikely that the criteria for registration of narrow therape...

Seven novel N-arylsulfonyl-3-(2-yl-ethanone)-6-methylindole derivatives 4a-f and 6 were readily synthesized and have been identified as inhibitors of human immunodeficiency virus type-1 (HIV-1) replication. Initial biological studies indicated that among these derivatives, N-(p-ethyl)phenylsulfonyl-3-[2-morpholinoethanone]-6-methylindole (4f) and N-(p-ethyl)phenylsulfonyl-3-[2-(5-phenyl-1,3,4-o...

BACKGROUND This preliminary study examined the effects of electrical stimulus intensity on the speed of response and efficacy of bilateral electroconvulsive therapy (ECT) in the treatment of schizophrenia. METHODS Sixty-two patients with schizophrenia received combination treatment with bilateral ECT and flupenthixol. Using a randomized, double-blind design, the effects of three dosages of th...

The artemisinins are the most effective antimalarial drugs known. They possess a remarkably wide therapeutic index. These agents have been used in traditional Chinese herbal medicine for more than 2,000 years but were not subjected to scientific scrutiny until the 1970s. The first formal clinical trials of the artemisinins, and the development of methods for their industrial scale production, f...

Juvenile idiopathic arthritis (JIA) is the most common autoimmune-autoinflammatory disease in childhood and affects approximately 1 in 1,000 children. Despite advances in diagnosis and treatment options, JIA remains a chronic condition for most affected children. Recent evidence suggests that disease control at onset may determine the tempo of subsequent disease course and long-term outcomes, a...

BACKGROUND AND PURPOSE Arterial recanalization and subsequent reperfusion have extensively demonstrated their ability to restore the brain function when performed shortly after acute ischemic stroke. However, arterial recanalization does not necessarily lead to brain tissue reperfusion. SUMMARY OF REPORT This review provides an update of current approaches to improve the efficacy profile of b...

A knowledge of the concentration of a drug in blood or other tissue fluid is now considered an important and sometimes essential part of the therapeutic management of various conditions. Its importance has increased as information showing wide interindividual variation in drug response has become recognised. Such variation arising from differences in absorption, distribution, and elimination ap...

Anticancer agents often have a narrow therapeutic index (TI), requiring precise dosing to ensure sufficient exposure for clinical activity while minimizing toxicity. These agents frequently have complex pharmacology, and combination therapy may cause schedule-specific effects and interactions. We review anticancer drug development, showing how integration of modeling and simulation throughout d...