Measuring Blood Pulse Wave Velocity with Bioimpedance in Different Age Groups.

In this project, we have studied the use of electrical impedance cardiography as a possible method for measuring blood pulse wave velocity, and hence be an aid in the assessment of the degree of arteriosclerosis. Using two different four-electrode setups, we measured the timing of the systolic pulse at two locations, the upper arm and the thorax, and found that the pulse wave velocity was in general higher in older volunteers and furthermore that it was also more heart rate dependent for older subjects. We attribute this to the fact that the degree of arteriosclerosis typically increases with age and that stiffening of the arterial wall will make the arteries less able to comply with increased heart rate (and corresponding blood pressure), without leading to increased pulse wave velocity. In view of these findings, we conclude that impedance cardiography seems to be well suited and practical for pulse wave velocity measurements and possibly for the assessment of the degree of arteriosclerosis. However, further studies are needed for comparison between this approach and reference methods for pulse wave velocity and assessment of arteriosclerosis before any firm conclusions can be drawn.

Early effects of high concentrations of progesterone and mifepristone A gene expression study of endometrial cancer cells (Ishikawa).

Patients with endometrial hyperplasia representing preliminary stages of endometrial cancer have shown to respond to therapy in 100% of the cases when treated with levonorgestrel-impregnated intrauterine device. Anti-proliferative effect has also been reported after application of an anti-progestin impregnated intrauterine device which showed to induce endometrial atrophy. The intention of the present study was to obtain more information of novel therapeutic targets for hormonal treatment in endometrial hyperplasia and endometrial cancers. Gene expression of signaling pathways after stimulation of Ishikawa cells with high doses of progesterone (32 microM) or Mifepristone (32 microM) was performed. After using an oligo microarrays representing 24,650 human genes and 37,580 gene transcripts, 6154 genes remained after pre-processing and filtering. This resulted in a total of 993 up-regulated genes with 189 genes for progesterone and 255 genes for Mifepristone. The 550 down-regulated genes were distributed with 256 genes for progesterone, 127 genes for RU 486. The results showed that genes presenting the epidermal growth factor (EGF)/MAP-kinase pathway were significantly over-represented by progesterone treatment, whereas, by Mifepristone treatment genes involved in the p53 pathway were also up-regulated (data not shown). These genes may be interesting as potential new therapeutic targets in endometrial hyperplasia and endometrial cancer, as candidate genes for therapy response or as candidate markers for tumor progression.

Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone.

The potent antiproliferative effect of progestins has been utilized in clinical regimens for treatment of endometrial proliferative disorders. The progestin infiltrated intrauterine device used as therapy for endometrial carcinoma as well as endometrial hyperplasia yields a hundred-fold increase of local progestin concentration in the endometrium compared to that of oral treatment. The genetic basis for the complex effects of high dose progestins and the different signalling pathways regulated by these genes have never been accurately surveyed. The aim of the present study was to determine the gene expression pattern in highly differentiated endometrial cancer cells (Ishikawa) after short time exposure to high progesterone doses. In eight independent experiments, cells were treated with progesterone (30microg/ml) for 4h and gene expression was compared to that of untreated cells, which served as controls. Microarray analysis revealed 247 differentially expressed genes of which 126 were up-regulated and 121 were down-regulated. Of these, 135 genes are known to be involved in biological processes like cell cycle, cell proliferation and differentiation, developmental processes, immune responses, intracellular protein traffic and transport. Our study shows that microarray analysis can detect relevant gene expression changes in endometrial cells treated with progestin, including those involved in several alternative transcriptional factors and signalling pathways. Many of the differentially expressed genes were not previously known to be affected by progesterone or have unknown biological functions. Characterization of these genes may give new insights into molecular responses to treatment with high progesterone doses. Alternative signalling pathways for progesterone, rather than the classical steroid receptors pathways are also suggested.