Effects of Furanocoumarins from Apiaceous Vegetables on the Catalytic Activity of Recombinant Human Cytochrome P-450 1A2

Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens may be an important chemopreventive mechanism. Consumption of apiaceous vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many furanocoumarins are potent inhibitors of several CYPs, we characterized the effects of three furanocoumarins from apiaceous vegetables on human CYP1A2 (hCYP1A2). We assessed hCYP1A2 methoxyresorufin O-demethylase (MROD) activity using microsomes from Saccharomyces cerevisiae expressing hCYP1A2. Isopimpinellin exhibited mechanism-based inactivation (MBI) of hCYP1A2 (K _i  = 1.2 μM, k _inact = 0.34 min⁻¹, and partition ratio = 8). Imperatorin and trioxsalen were characterized as mixed inhibitors with K _i values of 0.007 and 0.10 μM, respectively. These results indicate that even if present at low levels in apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute significantly to CYP1A2 inhibition and potentially decreased procarcinogen activation. Moreover, the in vivo effect of isopimpinellin on CYP1A2 may be longer lasting compared to reversible inhibitors.     

Asymmetric competition between Rana clamitans and Hyla versicolor tadpoles

When two organisms interact over a potentially limiting resource, several outcomes are possible (e.g. neither affected, both equally affected, one affected more than the other). The outcome depends on a variety of factors, both internal and external to the organism. We performed a laboratory experiment to investigate the outcome of potential competitive interactions between tadpoles of the green frog ( Rana clamitans ) and the gray treefrog ( Hyla versicolor ), and to examine the factors that may explain the outcome of the interaction. We found that competition between these two species was asymmetric. Hyla versicolor tadpoles were more affected by intraspecific competition than interspecific competition (i.e. grew faster when grown with heterospecifics than conspecifics); whereas, R . clamitans tadpoles were more affected by interspecific competition than intraspecific competition (i.e. grew faster when grown with conspecifics than heterospecifics). Based on behavioral observations, this result could not be explained on the basis of activity levels, a trait previously linked to competitive ability in tadpoles. However, differences in initial body size may help explain the observed results; the gray treefrog tadpoles were larger than the green frog tadpoles.     

Vaginally administered PGF2alpha for cervical dilatation in nulliparas prior to suction curettage

Because of the need for an atraumatic method to dilate the cervix when performing artificial abortion by suction curettage, cervical dilatation following vaginally administered PGF2alpha was studied. A 50 mg PGF2alpha vaginal suppository was administered to 40 (treated group) first trimester nulliparas 3 hours prior to progressive cervical dilatation from a 19 (circumference in mm) Pratt dilator to a 35 Pratt dialator. The smallest-sized dilator that met resistance was interpreted as being the amount of clinically significant cervical dilatation. The results were compared to 20 (control group) first trimester nulliparas who received no PGF2alpha studied in an identical manner. Independent of gestational age, treated patients were dilated significantly more than the control patients. When subjects of similar gestational age were compared, PGF2alpha treated subjects were more often dilated sufficiently to perform abortion (55%) by suction curettage than control group subjects (5%). Those PGF2alpha subjects needing further dilatation to accept an appropriate sized cannula for their gestational age needed less dilatation than did those subjects of similar gestational age in the control group. No serious complications of PGF2alpha per se were observed and the most frequent side effects, vomiting and diarrhea, did not appear severe enough to limit the clinical practicability of the method.     

The Bethe surface of liquid water

The Bethe surface of liquid water, which was previously calculated by using a semiempirical model, is compared with recently available data from IXS experiments (inelastic x-ray scattering; Compton scattering of high energy photons) in liquid water. No alarming discrepancy is found for a global view of the Bethe surface, in part because the two sets of data have been constrained by the Bethe sum rule. The shape of the Bethe ridge given by the new data is broader than that obtained through the impulse approximation. The extrapolation to the optical limit (viz., at zero momentum transfer) is shown, and the reliability of these data is discussed in detail. Received: 11 September 1998 / Accepted in revised form: 15 February 1999