Cocaine use in pregnancy in Amsterdam

To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine-using pregnant women ( n = 21) and their offspring ( n = 23) were obtained retrospectively (1987–1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks and a median birth weight of 3090 g. There were six preterm infants, two small-for-gestational-age infants and five infants with a small head circumference. Three infants had a congenital malformation. One infant (Potter's syndrome) died shortly before birth. One infant had congenital syphilis, four had intracerebral abnormalities on ultrasound and four had abnormal neurologic symptoms in the neonatal period. One infant died after 21 days of life. At follow-up four infants showed abnormal development. In 12 of the 23 infants (52%), one or more possible effects of cocaine were found.     

Novel actions of the antitumor drugs vinflunine and vinorelbine on microtubules

Vinflunine is a novel Vinca alkaloid presently in Phase I clinical trials. In preclinical studies, it exhibited superior antitumor activity to that of other Vinca alkaloids, including vinorelbine from which it was synthetically derived. Vinca alkaloids appear to inhibit cell proliferation by affecting the dynamics of spindle microtubules. Here we have analyzed the effects of vinflunine and vinorelbine on microtubule dynamic instability and treadmilling and found that these newer drugs exert effects on microtubule dynamics that differ significantly from those of the classic Vinca alkaloid, vinblastine. The major effects of vinflunine and vinorelbine on dynamic instability were a slowing of the microtubule growth rate, an increase in growth duration, and a reduction in shortening duration. In marked contrast to the action of vinblastine, they neither reduced the rate of shortening nor increased the percentage of time the microtubules spent in an attenuated state, neither growing nor shortening detectably. In addition, vinflunine and vinorelbine suppressed treadmilling, but less strongly than vinblastine. The diverse actions of these drugs on microtubules are likely to produce different effects on mitotic spindle function, leading to different effects on cell cycle progression and cell killing. Nontumor cells with normal checkpoint proteins may tolerate the relatively less powerful inhibitory effects of vinflunine and vinorelbine on microtubule dynamics better than the more powerful effects of vinblastine. Thus the unique constellation of effects of vinflunine and vinorelbine on dynamic instability and treadmilling may contribute to their superior antitumor efficacies.