Long-term intake of Korean red ginseng in HIV-1-infected patients: development of resistance mutation to zidovudine is delayed.

We have observed that CD4+ T cell counts in human immunodeficiency virus (HIV)-1-infected patients treated with only Korean red ginseng (KRG) are maintained or even increased for a prolonged period. In the present study, we investigated whether the development of resistance mutations in reverse transcriptase (RT) to zidovudine (ZDV) is delayed by combined therapy with KRG and ZDV. Nested polymerase chain reaction (PCR) and direct sequencing methods were used to define RT codons 41, 67, 70, 210, 215 and 219 of the HIV-1 pol gene in DNA from peripheral blood mononuclear cells (PBMC) samples from 18 patients. Nine of these eighteen patients were in the KRG group and had been treated with KRG for 60 +/- 15 months (range: 38-82) and ZDV, and nine were in the control group and had been treated with ZDV only. The patients in the KRG group had been treated with ZDV for 75 +/- 24 months, and CD4+ T cell counts were maintained from 239 +/- 85 to 234 +/- 187 microliters-1 (P > 0.05) during the study period, whereas the patients in the control group had been treated with ZDV for 51 +/- 31 months, and their CD4+ T cell counts decreased from 272 +/- 97 to 146 +/- 154 microliters-1 (P < 0.01). In samples within 24 months of ZDV therapy, the overall incidence of 6 resistance mutations to ZDV was 4.2% and 47% in the KRG and control group (P < 0.01), respectively. In samples after 24 months of therapy, the incidence was 21.7% and 56.3% in the KRG and control group (P < 0.01), respectively. These data suggest that the maintenance of CD4+ T cell counts by ZDV and KRG-intake for a prolonged period might be indirectly associated with delayed development of resistance to ZDV by KRG-intake.

TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion.

TTF-1 is a member of the Nkx family of homeodomain genes required for morphogenesis of the hypothalamus. Whether TTF-1, or other Nkx genes, contributes to regulating differentiated hypothalamic functions is not known. We now report that postnatal hypothalamic TTF-1 expression is developmentally regulated and associated with the neuroendocrine process of female sexual development. Lesions of the hypothalamus that cause sexual precocity transiently activate neuronal TTF-1 expression near the lesion site. In intact animals, hypothalamic TTF-1 mRNA content also increases transiently, preceding the initiation of puberty. Postnatal expression of the TTF-1 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, which restrain sexual maturation and facilitate reproductive behavior. TTF-1 mRNA was also detected in astrocytes of the median eminence and ependymal/subependymal cells of the third ventricle, where it colocalized with erbB-2, a receptor involved in facilitating sexual development. TTF-1 binds to and transactivates the erbB-2 and LHRH promoters, but represses transcription of the preproenkephalin gene. The singular increase in hypothalamic TTF-1 gene expression that precedes the initiation of puberty, its highly specific pattern of cellular expression, and its transcriptional actions on genes directly involved in neuroendocrine reproductive regulation suggest that TTF-1 may represent one of the controlling factors that set in motion early events underlying the central activation of mammalian puberty.