Doppler examinations of fetal and uteroplacental blood flow in AGA and IUGR fetuses before and after maternal physical exercise with the bicycle ergometer.

OBJECTIVE: To study changes in uteroplacental and fetal circulation after maternal exercise in appropriate-for-gestational-age fetuses (AGA) and intrauterine-growth-retarded fetuses (IUGR). MATERIALS AND METHOD: 33 women with an uncomplicated course of pregnancy and ten women with IUGR were examined. Physical stress was caused through a bicycle ergometer with 1.25 W/kg maternal weight. Doppler examinations were performed in the umbilical artery, fetal aorta, middle cerebral and in the uterine artery. Fetal heart rate was documented by monitoring. Maternal lactate and glucose levels as well as maternal blood pressure and heart rate were recorded. RESULTS: No significant changes after cycling could be observed in umbilical and uterine vessels either in the normal pregnancies or in pregnancies with IUGR. In contrast, in the fetal aorta an increase of the RI was recorded in both groups (an increase of 16% [P<0.01] and 18% [P<0.05], respectively for AGA and IUGR cases). In cerebral arteries a decrease of the RI was observed after cycling in both groups (a decrease of 24% [P<0.01] and 13% [P<0.05], respectively for AGA and IUGR cases). In AGA fetuses the RI of the aorta and middle cerebral artery returned to pre-test level by the 18th minute of examination. In IUGR fetuses the RI of the aorta and middle cerebral artery did not return to pre-test levels at the end of the test. Fetal heart rate remained unchanged in both groups. Maternal blood pressure and heart rate increased during the exertion phase but returned to initial values at the end of the test. A 21% and 24% (for AGA and IUGR groups respectively) reduction of maternal glucose values after exercise was observed (P<0.001). Lactate values doubled in both groups after exercise (P<0.001). CONCLUSION: From the results obtained we conclude that maternal exercise does not significantly alter uterine and umbilical perfusion in AGA and IUGR pregnancies, suggesting an absence of change in the uterine vascular bed resistance. However, submaximal maternal exercise was followed by fetal cerebral vasodilatation and an increase of resistance in the fetal aorta that was more evident in IUGR fetuses. This might be due to slight fetal hemoglobin desaturation in those cases.

Immunohistochemical analysis of 1,25-dihydroxyvitamin-D3-receptors, estrogen and progesterone receptors and Ki-67 in ovarian carcinoma.

BACKGROUND: The aim of this study was to analyze immunohistochemically the expression of VDR in normal and carcinomatous ovarian tissue to evaluate whether ovarian tissue may be a new potential target for biologically active vitamin D analogues. MATERIALS AND METHODS: The expression of 1,25-dihydroxyvitamin-D3-receptors (VDR) was immunohistochemically investigated in ovarian carcinomas (n=40). VDR immunoreactivity (mAb 9A7gamma) was compared with the staining pattern of the proliferation marker Ki-67, of the estrogen receptors (ER) and of the progesterone receptors (PR). The percentage of positive tumour cells (PP), the intensity of staining (SI) and a resulting immunoreactivity score (IRS) were determined for the semiquantitative evaluation of VDR-, ER- and PR-expression. RESULTS: A total of 16.7% of the normal surface ovarian epithelium was VDR-negative, while the remaining 83.3% revealed weak to moderate VDR immunoreactivity. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all ovarian carcinomas analyzed. Both the intensity of VDR immunostaining and the number of VDR-positive cells were significantly increased in ovarian carcinomas as compared to normal ovarian tissue. Analyzing coexpression of VDR with the proliferation marker Ki-67 or with the estrogen and progesterone receptors, no significant correlation was found. CONCLUSION: Our findings indicate that: (I) VDR expression is increased in ovarian carcinomas as compared to normal ovarian tissue. (II) Up-regulation of VDR in ovarian carcinomas is not exclusively induced by an increase of proliferation, but by different unknown mechanisms. (III) Expression of VDR in ovarian carcinomas is independently regulated from the expression of ER and PR. (IV) Ovarian tissue may be a new target organ for therapeutically applied vitamin D analogues exerting fewer calcemic side-effects. New vitamin D analogues may be promising drugs for the treatment of advanced ovarian carcinomas.

Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in cervical tissue.

UNLABELLED: 1,25(OH)2D3 suppresses proliferation and induces differentiation in various cell types, including epithelial cells. Recently, extrarenal activity of 1alpha-hydroxylase for 25(OH)D3 has been reported in various cell types including macrophages, keratinocytes and prostate and colon cancer cells. The aim of this study was to analyze the expression of 1alpha-hydroxylase for 25-hydroxyvitamin D3 in normal cervical samples and in cervical cancer, in order to investigate whether cervical tissue possesses the capacity to produce 1,25(OH)2D3 from 25(OH)D3, indicating that 1,25(OH)2D3 may be a locally produced hormone that controls proliferation in cervical tissue and that alterations in local production of 1,25(OH)2D3 may be involved in tumourigenesis of cervical cancer. MATERIALS AND METHODS: RNA was extracted from normal cervical tissue (n=4), cervical carcinomas (n=8) and HeLa cells using the method of Chomczynski. RNA was reverse-transcribed and RNA-levels were semiquantitatively detected by PCR. RESULTS: mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in more than 50% of samples analyzed in normal cervical tissue and in cervical cancer with no visible difference between either group. mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in HeLa cells as well. CONCLUSION: 25(OH)D3-1alpha-hydroxylase is expressed in normal cervical tissue, in cervical cancer and in HeLa cells. Thus, normal cervical and cervical cancer cells seem to be able to synthesize 1alpha, 25(OH)2D3 that may be of significant importance for the growth control in normal and malignant cervical tissue. Normal cervical tissue and cervical cancer cells may be new targets for cancer prevention or cancer treatment with precursors of biologically active vitamin D analogues.

Vitamin D receptor (VDR) expression is not a prognostic factor in cervical cancer.

BACKGROUND: The aim of this study was to analyze whether VDR status is a prognostic factor that may be of importance for the assessment of recurrence in cervical cancer. MATERIALS AND METHODS: VDR-, Ki-67- and p53-status were analyzed immunohistochemically in cervical cancer patients (n=50) and in benign cervical tissue (n=15). The histopathological data of the tumours were evaluated. RNA was extracted from normal cervical tissue (n=4) and cervical carcinomas (n=8) using the method of Chomczynski. RNA was reverse-transcribed and RNA-levels were semiquantitatively detected by PCR. RESULTS: The expression of VDR was significantly increased in cervical cancer compared to normal cervical tissue on the protein-level but not on the RNA-level. No statistically significant correlations were found comparing VDR status with histopathological data (tumour stage, lymph node status, grading, histological tumour type), with the expression of the proliferation marker Ki-67 and of the tumour suppressor gene p53. CONCLUSION: Our findings indicate that VDR protein expression is not a prognostic factor in cervical cancer. The strong I/DR immunoreactivity that we observed in cervical cancer specimens supports the body of evidence that cervical cancer may be a target for therapeutically applied vitamin D analogues.