Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 2: Ring-Substituted Derivatives

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development.     

Voltage Oscillations in Xenopus Spinal Cord Neurons: Developmental Onset and Dependence on Co-activation of NMDA and 5HT Receptors

The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg²⁺ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT_1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT₁, a selective 5HT_1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg²⁺, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg²⁺ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg²⁺ block. When the membrane potential was depolarized by ～20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg²⁺ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg²⁺ through activation of receptors with 5HT_1a-like pharmacology.     

Pediatric cerebellar hemorrhages

Cerebellar hemorrhage is a devastating condition with morbidity and mortality related not only to the etiology of the hemorrhage, but also to the timing of the intervention. Sixteen consecutive pediatric patients with acute cerebellar hemorrhages are presented: 6 had vascular abnormalities, 3 had tumors, and 2 had hemorrhages of unknown etiology. Thirteen of the 16 patients survived with only 1 of the 13 having persistent vegetative state as a neurologic outcome. Six of 8 patients presenting in a moribund condition had good outcomes, and 3 of 4 patients presenting with fixed and dilated pupils also had good outcomes. Thus, in contrast to adults, rapid evaluation by CT scanning, followed by the judicious use of ventricular drainage and prompt surgical treatment, have resulted in favorable outcomes in pediatric patients despite their poor clinical presentations. None of the neonates having cerebellar hemorrhages required surgical intervention; their courses could be followed clinically and with transfontanel ultrasound.Presented as a poster at the 14th Congress of the European Society for Paediatric Neurosurgery, Lyon, France, 21–23 September 1994, and the XXII Annual Meeting of the International Society for Pediatric Neurosurgery, Birmingham, UK, 25–28 September 1994     

An analysis of paramagnetic centers in irradiated dentin using electron spin resonance

Summary The ESR spectra produced in irradiated dentin have been studied over a range of incident radiation energies from 50 kVp to 25 MVp. The behavior of the dentin ESR signal strength is similar to that of enamel as a function of the energy of the incident radiation. The magnitude of the dentin ESR signals are, however, up to 10 times smaller than the signals of dental enamel for a given radiation energy. The possible contributions of radiation interaction coefficients, chemical structure, and crystallite size to the differences in ESR spectra are discussed.