DNA damage from polycyclic aromatic hydrocarbons measured by benzo[a]pyrene-DNA adducts in mothers and newborns from Northern Manhattan, the World Trade Center Area, Poland, and China.

Polycyclic aromatic hydrocarbons (PAH), of which benzo[a]pyrene is a representative member, are combustion-related environmental pollutants and include known carcinogens. Laboratory animal studies indicate that the dose of PAHs to the fetus is on the order of a 10th that to the mother and that there is heightened susceptibility to PAH-induced carcinogenesis during the fetal and infancy periods. Carcinogen-DNA adducts, a measure of procarcinogenic genetic damage, are considered a biomarker of increased cancer risk. Here we compare the levels of benzo[a]pyrene-DNA adducts as a proxy for PAH-DNA damage measured in maternal blood and newborn cord blood obtained at delivery in four different populations of mothers (total of 867) and newborns (total of 822), representing a 30-fold range of exposure to ambient PAHs. The populations include residents in Northern Manhattan, participants in a study of the effects of the World Trade Center disaster, residents in Krakow, Poland, and residents in Tongliang, China. Mean adduct concentrations in both maternal and cord blood and the proportion of samples with detectable adducts, increased across the populations [Northern Manhattan < World Trade Center (WTC) < Krakow < Tongliang], consistent with the trend in estimated ambient exposure to PAHs (P < 0.001). For mothers, the means in the respective populations were Northern Manhattan (0.21 adducts per 10(8) nucleotides), WTC (0.23 adducts per 10(8) nucleotides), Krakow (0.28 adducts per 10(8) nucleotides), Tongliang (0.31 adducts per 10(8) nucleotides); the corresponding means in the newborns were Northern Manhattan (0.23), WTC (0.24), Krakow (0.29), Tongliang (0.31). The percentage of mothers with detectable levels of adducts in the respective populations were Northern Manhattan (36.8%), WTC (57.5%), Krakow (72.9%), Tongliang (73.4%); the corresponding percentages among the newborns were Northern Manhattan (42.4%), WTC (60.6%), Krakow (71.1%), Tongliang (79.5%). Despite the estimated 10-fold lower PAH dose to the fetus based on laboratory animal experiments, the adduct levels in the newborns were similar to or higher than in the mothers. This study suggests that the fetus may be 10-fold more susceptible to DNA damage than the mother and that in utero exposure to polycyclic aromatic hydrocarbons may disproportionately increase carcinogenic risk. The data support preventive policies to limit PAH exposure to pregnant women and children.     

Cytokines and growth factors in keratinocytes and sweat glands in chronic venous leg ulcers. An immunohistochemical study

The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing.     

Changing antibiotic sensitivity patterns in shigellosis.

Over five and a half months stool cultures were performed in 154 patients admitted with suspected bacillary dysentery to the Professorial Paediatric Unit of the Teaching Hospital, Galle. Thirty one patients had a positive stool culture; Shigella dysenteriae type 1 was isolated in 23 patients, and S flexneri in 8. In both groups the antibiotic sensitivity pattern was uniform, the only difference being S dysenteriae type 1 being resistant to nalidixic acid while S flexneri was sensitive. This antibiotic sensitivity pattern was different to that reported from Colombo during the same period. Complications were observed in some patients with S flexneri infection.     

Variation in hypothalamic gonadotrophin-releasing hormone content, plasma and pituitary LH, and in-vitro testosterone release in a long-distance migratory bird, the garden warbler (Sylvia borin), under constant photoperiods

Changes in concentrations of hypothalamic gonadotrophin-releasing hormone (GnRH), pituitary and plasma LH, testicular mass, in-vitro release of testosterone, body mass and migratory activity were measured in male garden warblers (Sylvia borin) kept from November to June under a constant photo-period of 12.8 h. Under such conditions garden warblers gradually change from the photorefractory to the photosensitive state and gonadal recrudescence then occurs. Hypothalamic GnRH content was low from December to March, but increased in April to reach the highest levels in June. The spontaneous increase in GnRH was paralleled by increases in pituitary LH content, testicular mass and in-vitro testosterone release. Body mass decreased 1 month and nocturnal activity 2 months before the spontaneous increase in GnRH. Ovine LH increased in-vitro testosterone release over basal release at all times. The results suggest that in garden warblers (1) changes in hypothalamic GnRH content can occur under constant photoperiodic condition, (2) the gradual change from the photorefractory to the photosensitive state is not characterized by a gradual increase in hypothalamic content of GnRH (cf. starlings), and (3) Leydig cells are capable of testosterone release even during the photorefractory state.