The effect of postnatal undernourishment on epileptiform kindling of dorsal hippocampus

Summary Rats were undernourished postnatally from birth through 20 days of age. They were subsequently tested for susceptibility to motor seizures kindled in hippocampus in adulthood. Compared to littermate control animals the postnatally undernourished rats were more susceptible to the kindling treatment. We conclude that early postnatal undernourishment has a permanent effect on susceptibility of the hippocampus to electrically-induced seizures.This work was supported by Public Health Service grant NS 13799, National Science Foundation grant GB 35532, and by Hoffman-LaRoche, Inc.     

Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production

The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF1 alpha and TxB2 was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5 x 10(-3) to 5 x 10(-7) g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented.     

A note on diagrams for turning-point diagnostics

A new diagram for discriminating a forecasting technique's history with respect to the two types of turning-point errors, missed turns and false signals is presented. This diagram extends Theil's original prediction-realization (P-R) presentation so that each of the four quadrants and the axes locates a distinct type of forecasting error or correct forecast, thus reducing much of the former ambiguity. This improvement is accomplished without the loss of any information.     

Pressor response to angiotensin I during cardio-pulmonary bypass

Résumé La réponse pressive systémique à des injections intra-artérielles d'angiotensine I et II a été étudiée chez deux chiens avant et après avoir totalement exclu les poumons de la circulation. La réactivité à l'angiotensine I diminua presque 3 fois plus que celle à l'angiotensine II durant le shunt cardio-pulmonaire. Il apparaÎt donc que la circulation pulmonaire est un site important mais non exclusif de conversion de l'angiotensine I.     

A small-molecule screen in C. elegans yields a new calcium channel antagonist

Small-molecule inhibitors of protein function are powerful tools for biological analysis and can lead to the development of new drugs. However, a major bottleneck in generating useful small-molecule tools is target identification. Here we show that Caenorhabditis elegans can provide a platform for both the discovery of new bioactive compounds and target identification. We screened 14,100 small molecules for bioactivity in wild-type worms and identified 308 compounds that induce a variety of phenotypes. One compound that we named nemadipine-A induces marked defects in morphology and egg-laying. Nemadipine-A resembles a class of widely prescribed anti-hypertension drugs called the 1,4-dihydropyridines (DHPs) that antagonize the alpha1-subunit of L-type calcium channels. Through a genetic suppressor screen, we identified egl-19 as the sole candidate target of nemadipine-A, a conclusion that is supported by several additional lines of evidence. egl-19 encodes the only L-type calcium channel alpha1-subunit in the C. elegans genome. We show that nemadipine-A can also antagonize vertebrate L-type calcium channels, demonstrating that worms and vertebrates share the orthologous protein target. Conversely, FDA-approved DHPs fail to elicit robust phenotypes, making nemadipine-A a unique tool to screen for genetic interactions with this important class of drugs. Finally, we demonstrate the utility of nemadipine-A by using it to reveal redundancy among three calcium channels in the egg-laying circuit. Our study demonstrates that C. elegans enables rapid identification of new small-molecule tools and their targets.