Modern medical practice relies heavily on the use of highly purified pharmaceutical compounds whose purity can be easily assessed and whose pharmaceutical activity and toxicity show clear structure-function relationships. In contrast, many herbal medicines contain mixtures of natural compounds that have not undergone detailed chemical analyses and whose mechanism of action is not known. Traditional folk medicine and ethno-pharmacology coupled to bioprospecting have been an important source of many anticancer agents as well as other medicines. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicine. As the example of medicinal mushrooms demonstrates, however, translating traditional Eastern practices into acceptable evidence-based Western therapies is difficult. Different manufacturing standards, criteria of purity, and under-powered clinical trials make assessment of efficacy and toxicity by Western standards of clinical evidence difficult. Purified bioactive compounds derived from medicinal mushrooms are a potentially important new source of anticancer agents; their assimilation into Western drug discovery programs and clinical trials also provides a framework for the study and use of other traditional medicines.

The impact of mycotoxins on human and animal health is now increasingly recognised. Mycotoxin entry to the human and animal dietary systems is mainly by ingestion but increasing evidence also points at entry by inhalation. Mycotoxins exhibit a wide array of biological effects and individual mycotoxins can be mutagenic, carcinogenic, embryotoxic, teratogenic, or oestrogenic. Average levels of ingestion of currently known mycotoxins in most EEC countries are rather low. Little is known about the consequences to humans of such mycotoxin intakes. Establishing a causal relationship between mycotoxin exposure and human disease is complicated by uncertainties associated with human epidemiological studies. Analysis of mycotoxin adducts in human populations can act as a surrogate for human genotoxicity. Mycotoxins can also be immunosuppressive and appear to involve cellular immune phenomena and non-specific humoral factors associated with immunity.

A B S T R A C T Four normal men were injected intravenously with physiological doses (6 ltg) of vitamin Ds-1,2-2H. Serial

S U M M A R YThe ability of Aspergillus niger conidia to produce conidiophores after germination in shaken culture at 30" was stimulated by the inclusion of glutamate in the medium. Incubation of the conidia at 35" to 41" increased swelling of the conidia and also the proportion which produced conidiophores. Although conidio phore initiation was stimulated at temperatures between 35" and 41 ", maturation was poor and optimum conidiation was obtained by incubation at these temperatures followed by 30". Conidiophore formation from conidia required a prior period of spore metabolism and at temperatures between 30" and 41 " did not occur until several hours after germination. Direct conidiophore production from conidia in the complete absence of vegetative growth was achieved by incubation of the conidia at 44" (which allows only swelling) for a prolonged period (48 h.) followed by 30". Although vegetative growth was absent the conidiophores were similar to, but smaller than, normal subaerial conidiophores and viable conidia were produced. These conidia differed from subaerial spores in lacking the dark pigmented spore coat.

Studies were conducted to examine in detail the effects of vitamin A deficiency on fetal growth and development in the rat. The gradations of deficiency were examined in two studies. The first included total vitamin A depletion followed by retinoic acid supplements, and the second included three different levels of restricted intake of retinyl acetate (42, 16, or 8 mug of retinol equivalents/day/kg of body weight) in vitamin A-depleted rats. In the first study, extensive fetal resorption and death were observed in retinoic acid-fed females after day 14 of gestation. These findings confirmed the morphological studies of Thompson and associates (Proc. Roy. Soc. London, Ser. B 159, 510-535, 1964) who found the earliest Detectable histological lesions to be in the placentas at days 15-16 of pregnancy. Analyses were carried out of the total weight, the DNA, RNA, and protein contents of fetuses and placentas of different gestational ages in retinyl ester-fed and retinoic acid-fed females. Biochemical changes indicative of a reduced rate of cell division were observed in both fetus and placenta by day 14 in the retinoic acid-fed rats. The few live fetuses in this group maintained a growth rate of only 60-70% of that of the fetuses of retinyl ester-fed dams after day 14. By contrast, the growth rate of the placentas (of live fetuses) after day 14 of gestation was not as consistently affected by retinol deficiency. Restriction of retinyl acetate intake (in the second study) significantly reduced both the total litter size and the number of live pups per litter. Most of the females in the retinyl acetate-restricted groups delivered pups that had normal body weight and appeared normal on visual inspection. Significant differences from normal controls were seen only in the neonates from dams given 8 mug of retinol equivalents (per kg of body weight per day), which had smaller livers and kidneys than the control neonates. In contrast, the weights of the brains of the neonates in all three retinyl acetate-restricted groups showed no differences from control values. Vitamin A assays on maternal and neonatal sera and livers indicated that the transport of vitamin A across the placenta was well regulated, and suggested that this transport is maintained with high priority in the presence of maternal deficiency. The effects of vitamin A deficiency on fetal growth and development might reflect primary effects on the placenta, with secondary effects on the fetus, or primary direct effects on the fetus itself. The mechanisms of the observed effects remain to be explained.