Recent developments in antibacterial drug discovery: microbe-derived natural products--from collection to the clinic

The pharmaceutical industry has historically relied on nature to provide compounds for antibacterial drug discovery. In recent years, several pharmaceutical companies have scaled back their efforts in natural product research. Nevertheless, the screening of natural products for antibacterial activity continues to provide excellent sources of biologically and chemically informative leads for new drugs. New technologies in high-throughput cultivation, genetic approaches to biodiversity and discovery of relatively untapped sources of natural products are expanding the ability to find novel, potent and highly selective antibacterial structures. Advances in purification, dereplication and structure elucidation, combined with the ability to chemically or biologically derivatise hits, aim to make the timeline for natural product-derived drug discovery similar or shorter than that expected for small synthetic molecules. This review addresses the strengths and shortcomings of technologies focused on microbe-derived natural products for antibacterial drug discovery and stresses the need for commitment to these approaches in order to achieve the goal of delivering safe, efficacious and high-quality medicines in the long run.     

Infantile spasms in Down syndrome: a report of 5 cases and review of the literature.

Five patients with Down syndrome (DS) and infantile spasms were examined in a four-year interval. Previous reports of this association have been infrequent except during experimental treatment with 5-hydroxytryptophan, a precursor of serotonin. Malformations of the brain in DS are associated with an increased incidence of epilepsy, and both gross and cytoarchitectural anomalies have been described. The severity and distribution of these central nervous system anomalies presumably predispose to the infantile spasms. The contribution of altered serotonin metabolism is uncertain.     

Urinary Excretion of I131-Diodrast Injected Intraventricularly in Communicating Hydrocephalus and Aqueduct Stenosis

Nine cases of expansive infantile hydro-cephalus were investigated by injecting Small amounts of I¹³¹-Diodrast intra-ventricularly. Urinary excretion of the tracer was determined during the first 4-5 hours after injection. The cumulative excretion of Diodrast from the C.S.F. differs in cases with communicating hydrocephalus from those with stenosis of the aqueduct. The investigation is rapid and easily performed and has not produced any side effects.     

Primary cerebral lymphoma in acquired immunodeficiency syndrome (AIDS)--CT manifestations

Primary lymphoma of the brain in AIDS is being observed with increased frequency; five pathologically proven cases are presented. Although the CT patterns may correlate well with patterns previously described in lymphoma, occasionally an irregular ring-like lesion may occur which is difficult to distinguish from toxoplasmosis or other inflammatory processes without appropriate pathological material.