Modelling the impact of HIV on the populations of South Africa and Botswana.

We develop and use mathematical models that describe changes in the South African population over the last decades, brought on by HIV and AIDS. We do not model all the phases in HIV progression but rather, we show that a relatively simple model is sufficient to represent the data and allows us to investigate important aspects of HIV infection: firstly, we are able to investigate the effect of awareness on the prevalence of HIV and secondly, it enables us to make a comparison between South Africa and Botswana. A comparison is made between two models: a model that does not reflect awareness of the devastating impact of HIV and AIDS, and a model with an added psychological awareness factor. Both models are fitted to data that reflects the incidence of HIV and AIDS within South Africa. This allows us to examine the impact of psychological awareness. We show that inclusion of the effect of awareness is absolutely necessary to arrive at a model description that satisfactorily fits the available HIV and AIDS data for South Africa. We also show that a relatively simple modelling of awareness (as opposed to more complex mathematical techniques that have been used in past studies) is sufficient to accurately describe the observed patterns in the data. Even though awareness alone is not sufficient to eradicate any disease and other control strategies should be explored and implemented concurrently with educational campaigns, we are able to conclude (through thorough model analyses procedures) that the current level of awareness in South Africa is far below the level that is effectively required to eradicate HIV from the South African population. The awareness model is also fitted to HIV-related data for Botswana and we compare the results with the South African case. Though the effect of awareness is currently estimated at a much higher level in Botswana, other factors such as poorer health care and cultural differences may play a role in limiting the ability of awareness to combat HIV in Botswana.

17beta-Estradiol metabolites affect some regulators of the MCF-7 cell cycle.

The activity of p34(cdc2) plays a key role in the regulation of the eukaryotic cell cycle. Another cell cycle associated molecule is PCNA. We investigated the effects of 2-hydroxy-17beta-estradiol, a cell proliferator, and 2-methoxy-17beta-estradiol, a potent inhibitor of cell growth, on the levels and activity of p34(cdc2) and on the levels of PCNA, as well as on protein phosphorylation in MCF-7 cells. 2-Hydroxyestradiol increased p34(cdc2) activity at G1/S and elevated PCNA levels during S-phase. 2-Methoxyestradiol caused unscheduled activation of p34(cdc2) in S-phase and decreased levels of p34(cdc2) and PCNA during G2/M. We conclude that 2-hydroxy- and 2-methoxyestradiol have definite, though different regulatory functions during the cell cycle.

The induction of apoptosis in human cervical carcinoma (HeLa) cells by gamma-linolenic acid.

A high concentration (50 micrograms/ml) of gamma-linolenic acid (GLA) induced morphological lesions typical of apoptosis, as well as DNA fragmentation, in HeLa cells. A lower concentration of GLA (20 micrograms/ml), caused an increased proliferating cell nuclear antigen (PCNA) labelling, with 92.7% cells positive, compared to 27.7% at a concentration of 50 micrograms/ml GLA. In correlation with these results, the number of cells with degraded DNA below the G0/G1 peak increased significantly in the 50 micrograms/ml GLA-treated cells, but increased only slightly in cells exposed to the lower level of GLA. The high levels of PCNA induced by 20 micrograms/ml GLA, in both G1 and S phases, may indicate a state of DNA repair synthesis, whilst at the higher concentration of GLA, most of the cells became apoptotic. Since apoptosis is associated with the deregulation of c-Myc expression, and as the Raf-1-MAP kinase cascade activates the expression of c-Myc and c-Jun, we investigated the effects of 20 and 50 micrograms/ml GLA on the Raf-1, c-Myc and c-Jun levels, and on the activity of MAP kinase. The results showed that 50 micrograms/ml GLA lowered the activity of MAP kinase. As expected with the decreased MAP kinase activity in the cells exposed to the higher level GLA, the c-Jun levels were also lowered. The levels of c-Myc, however, were increased. It is therefore possible that the deregulated expression of c-Myc in the HeLa cells exposed to the high level of GLA (50 micrograms/ml) may contribute to the induction of apoptosis in HeLa cells.

Influence of acetylsalicylic acid and metabolites on DU-145 prostatic cancer cell proliferation.

Conflicting reports have been published on the anti-tumour activities of acetylsalicylic acid in various cancers. Therefore, the effect of acetylsalicylic acid and its major metabolites has been studied on human prostatic carcinoma DU-145 cells. Investigations concentrated on the influence of acetylsalicylic acid, salicylic acid and salicyluric acid, on cell proliferation, DNA- and protein synthesis of DU-145 cells. DNA and protein synthesis determinations were done in vitro by [3H]thymidine and [3H]glycine incorporation, respectively. No effect on cell plating efficiency was observed, however proliferation studies showed that acetylsalicylic acid and salicylic acid inhibited cell growth (10 mM, 100% inhibition). No significant effect on cell proliferation was ascertained with salicyluric acid. Both DNA and protein synthesis were 40% inhibited by 0.1 mM acetylsalicylic acid. This study demonstrates that acetylsalicylic acid exhibits a significant influence on cell growth of prostatic DU-145 cells. These preliminary results may contribute to a better understanding of the anti-tumour capabilities of acetylsalicylic acid.

Binding of estradiol to whole prostatic DU-145 cells in the presence and absence of tamoxifen and acetylsalicylic acid.

Conflicting results have been obtained with regard to the estradiol receptor (ER) capacity of human prostatic tissue. Human prostatic DU-145 cells have been found to be ER-negative with immunohistochemical assays. The object of this investigation was to determine if whole DU-145 cells, which had been grown in monolayer culture, have ER and, if so, to confirm the finding with antiestrogens. After cells had been lysed, a Bmax of 44.7 +/- 4.0 fmol/mg (Kd = 0.6 +/- 0.6 nM) was obtained. Subcellular localization studies showed that the estrogen receptor level in the cytoplasmic fraction was approximately 10 times higher than in the nuclear fraction. Competitive binding studies showed that tamoxifen, DES, and acetylsalicylic acid decreased estradiol binding. The dissociation constants and relative affinities for tamoxifen, DES, and acetylsalicylic acid were 0.2 nM (281.7%), 0.2 nM (224.0%), and 0.8 nM (78.43%), respectively. However, 5 alpha-dihydrotestosterone and metabolites of acetylsalicylic acid had no effect in competitive binding studies. These results may contribute to a better understanding of prostatic carcinogenesis, which may in turn lead to more effective treatment.