Publications

Hepatic stellate cells are resistant to the fibrogenic effects of lipid hydroperoxides in primary culture. Recent studies from our laboratory suggest that antioxidants, particularly glutathione, play a role in this resistance. We have observed that glutathione accumulates rapidly in stellate cells during primary culture; in the current study, we investigated whether glutathione modulates stellate cell collagen synthesis. Stellate cells from normal rat liver were plated in primary culture and maintained for 7 days. From day 4 through day 7, the cells were treated with L-buthionine sulfoximine (BSO) to deplete glutathione stores. BSO profoundly diminished stellate cell glutathione but had no effect on morphology, viability, or basal levels of collagen synthesis and gene expression. When cultured stellate cells were incubated with the putative fibrogenic mediator 4-hydroxynonenal or iron/ascorbate, little or no increase in collagen synthesis occurred regardless of glutathione content. In contrast, iron/ascorbate induced collagen synthesis by cultured fibroblasts. The data indicate that stellate cells strongly resist oxidant- and lipid peroxide-induced collagen synthesis in primary culture. They demonstrate that the mechanism of this resistance does not involve glutathione.

OBJECTIVES

To determine the prevalence of HIV and syphilis and related risk behavior in a sample of truck drivers in Santos, Brazil.

SUBJECTS AND METHODS

A cross-sectional study was performed of 300 male truck drivers recruited in the port of Santos, Brazil, including a face-to-face interview and blood sampling for HIV and syphilis serology.

RESULTS

Of 300 subjects, 4 (1.3%) were positive for HIV, 25 (8.3%) for syphilis by the Venereal Disease Research Laboratory (VDRL) test and 38 (13%) were positive for syphilis by the fluorescent treponemal antibody (absorbed) test (FTA-Abs). Seventy-one per cent had been employed as truck drivers for more than 10 years and 93% lived outside of Santos. Most participants were married (72%); 40% reported having more than one sex partner; 21% reported sex with commercial sex workers; 14% reported sex with girls that they met on the road; 16% had sex with other men's wives; and 3.3% reported sex with men during the past year. The use of rebite, an oral stimulant, was reported by 43% and was associated with being FTA-Abs-positive (P = 0.04). Being HIV-positive was associated with having sex with friends (P = 0.04), partners usually considered 'safe' by truck drivers. Being syphilis-positive (VDRL) was significantly associated with sex with partners also considered as 'safe', namely primary sex partners, steady partners and other men's wives.

DISCUSSION

This is the first study to determine HIV and syphilis seroprevalence among truck drivers in South America. Findings confirm that this group has a high potential risk for HIV infection and other sexually transmitted diseases, and thus currently presents an opportunity for prevention.

Nuclear factor kappaB (NF-kappaB) is a eukaryotic member of the Rel family of transcription factors whose biological activity is post-translationally regulated by its assembly with various ankyrin-rich cytoplasmic inhibitors, including IkappaBalpha. Expression of NF-kappaB in the nucleus occurs after signal-induced phosphorylation, ubiquitination, and proteasome-mediated degradation of IkappaBalpha. The induced proteolysis of IkappaBalpha unmasks the nuclear localization signal within NF-kappaB, allowing its rapid migration into the nucleus, where it activates the transcription of many target genes. At present, the identity of the IkappaBalpha kinase(s) that triggers the first step in IkappaBalpha degradation remains unknown. We have investigated the potential function of the 90-kDa ribosomal S6 kinase, or pp90(rsk), as a signal-inducible IkappaBalpha kinase. pp90(rsk) lies downstream of mitogen-activated protein (MAP) kinase in the well characterized Ras-Raf-MEK-MAP kinase pathway that is induced by various growth factors and phorbol ester. We now show that pp90(rsk), but not pp70(S6K) or MAP kinase, phosphorylates the regulatory N terminus of IkappaBalpha principally on serine 32 and triggers effective IkappaBalpha degradation in vitro. When co-expressed in vivo in COS cells, IkappaBalpha and pp90(rsk) readily assemble into a complex that is immunoprecipitated with antibodies specific for either partner. While phorbol 12-myristate 13-acetate produced rapid activation of pp90(rsk), in vivo, other potent NF-kappaB inducers, including tumor necrosis factor alpha and the Tax transactivator of human T-cell lymphotrophic virus, type I, failed to activate pp90(rsk). These data suggest that more than a single IkappaBalpha kinase exists within the cell and that these IkappaBalpha kinases are differentially activated by different NF-kappaB inducers.