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Breast-fed infants are susceptible to human cytomegalovirus (HCMV) infection via breast milk. In our previous study, HCMV was isolated more frequently from breast milk at later than one month after delivery than from colostrum or early breast milk. To clarify the role of milk cells and whey in vertical infection by breast feeding, we separated breast milk into milk cells and whey and examined each fraction for the presence of HCMV. We collected breast milk from mothers who breast-fed their infants (aged from 3 days to 2 months). The breast milk was centrifuged and separated into the middle layer (layer of milk whey) and the pellet (containing milk cells). We attempted to isolate HCMV from whey and to detect HCMV immediate early (IE) DNA in both milk whey and cells. HCMV was isolated from 7 out of 35 (20.0%) whey samples and HCMV IE DNA was detected from 15 out of 35 (42.9%) whey and/or milk cells. Detection rates of HCMV IE DNA in the whey layer and milk cells were 39.1% (25 out of 64) and 17.2% (11 out of 64), respectively. HCMV IE DNA was not detected in colostrum, but was detected in breast milk samples one month after delivery. Therefore, cell-free HCMV shed into milk whey may have a more important role in vertical infection by breast milk than cell-associated HCMV in the milk. Human cytomegalovirus (HCMV) infection occurs by vertical, horizontal and iatrogenic transmission. In Japan, over 90% of healthy adults acquire the HCMV IgG antibody and over 60% of healthy infants are infected with HCMV during the first year of life (15). Vertical transmission includes transplacental transmission, transmission due to contact with virus-containing secretion in the birth canal, and transmission by feeding infected breast milk. Transplacental transmission that was assessed by viruria of neonates is assumed to have an incidence of 0.2-2.2%. In Japan, as 11-28% of pregnant women in the late stage of gestation shed HCMV into genital tract secretions (15), genital tract secretion was regarded as a main source of infection. Since Diosi et al (5) succeeded in isolating HCMV from breast milk, breast milk has been considered as one of the most important sources of mother-to-infant infection. Hayes et al (7) isolated HCMV from breast milk of 17 out of 64 seropositive women (27%) and most of the isolates were obtained after the first week. Stagno et al (17) reported that breastfed infants are more frequently infected with HCMV than bottle-fed infants based on the rate of isolation from urine. Moreover, Dworsky et al (6) reported that consumption of infected breast milk led to infection in 69% of infants. Isolation of HCMV from colostrum showed a lower incidence than breast milk at more than one month after delivery. Breast feeding seemed to be associated more closely with vertical infection than contact with an infected genital tract. In past studies of our laboratory, Hotsubo et al (8) reported the results of virus isolation and the detection of HCMV DNA for late antigen (LA) in milk samples of seropositive mothers a...

1 We have investigated the mechanism of capsaicin-induced mouse ear oedema compared with that of arachidonic acid (AA)-induced ear oedema, and evaluated the possible involvement of neuropeptides in the development of capsaicin-induced oedema. 2 Topical application of capsaicin (0.1-1.0 mg per ear) to the ear of mice produced immediate vasodilatation and erythema followed by the development of oedema which was maximal at 30 min after the treatment. This oedema was of shorter duration with less swelling than AA-induced oedema (2.0 mg per ear). 3 Capsaicin-induced ear oedema was unaffected when inhibitors of arachidonate metabolites including platelet activating factor (PAF) were administered before capsaicin (250 jg per ear) application, while these agents significantly prevented AA-induced oedema. Dexamethasone, histamine HI and/or 5-hydroxytryptamine (5-HT) antagonists, and substance P (SP) antagonists were effective in inhibiting both models. Furthermore, a Ca2+-channel blocker and the capsaicin inhibitor, ruthenium red, were effective inhibitors of capsaicin oedema but had no effect on AA-induced oedema.4 Phosphoramidon (50 jig kg-', i.v.), an endopeptidase inhibitor, markedly (P<0.001) enhanced only capsaicin-induced ear oedeima, but bestatin (0.5mgkg-', i.v.), an aminopeptidase, failed to enhance oedema formation. 5 Neuropeptides (1-100 pmol per site) such as rat calcitonin gene-related peptide (CGRP), SP, neurokinin A (NKA), and vasoactive intestinal peptide (VIP), which are released from capsaicinsensitive neurones, caused ear oedema by intradermal injection. Furthermore, a synergistic effect of CGRP (10fmol per site) and SP (1Opmol per site) on oedema formation was observed.6 The oedema induced by neuropeptides was significantly (P<0.05 or P<0.001) inhibited when cyproheptadine (20 mg kg-', p.o.), a histamine H, and 5-HT antagonist, was administered before injection. In contrast, nifedipine (50 mg kg-', p.o.), a Ca2'-channel blocker, and indomethacin (10 mg kg-', p.o., except for NKA), a cyclo-oxygenase inhibitor, had little effect on neuropeptideinduced oedema. 7 These results suggest that the mechanism of capsaicin-induced ear oedema is different from that of AA-induced oedema and suggest that the development of capsaicin-induced ear oedema is primarily mediated by neuropeptides. The neuropeptides released after activation of sensory nerves cause an increase of vascular permeability by interactions with endothelial cells and by histamine release from mast cells.