Biomedical subjects

S Saarikoski

Publications and source records attributed to S Saarikoski.

At least 19 recordsLinked to original sources

PubMed1999

Failure to demonstrate human papillomavirus DNA in epithelial ovarian cancer by general primer PCR.

One of the recent controversies with substantial clinical interest is the role of HPV in pathogenesis of ovarian cancer. The available highly conflicting data are based on analysis of 175 ovarian carcinomas so far. As an attempt to further elucidate this issue, the first systematic study of HPV detection in ovarian cancer was carried out using a highly sensitive general primer PCR (confirmed by hybridization for low- and high-risk HPV types separately) in a series of 98 histologically and clinically well-characterized epithelial ovarian malignancies. Despite the high (fg) sensitivity and a wide HPV type coverage of the technique used, all 98 ovarian carcinomas failed to demonstrate any signs of HPV DNA whatsoever. The preexisting 12 reports comprising a total of 175 ovarian tumors analyzed for HPV were summarized, giving highly discrepant results (i.e., detection rates from 0 to 100%) with the overall HPV DNA detection rate of 25.7%. The reasons for these discrepant findings are most probably technical. Our data are consistent with those of the majority of the most recent reports failing to disclose HPV DNA in ovarian neoplasia. The present completely negative results make the authors inclined to conclude that HPV is highly unlikely to play any causal role in the pathogenesis of epithelial ovarian neoplasia.

Adenocarcinoma↗

PubMed1999

Is the response of serum lipids and lipoproteins to postmenopausal hormone replacement therapy modified by ApoE genotype?

Postmenopausal hormone replacement therapy (HRT) has favorable effects on the serum lipid profile, and it also decreases the risk of cardiovascular diseases. The apolipoprotein E genotype has influence on serum levels of lipids and lipoproteins; apoE allele epsilon4 (apoE4) is associated with high total and LDL cholesterol levels. Genotype also influences the lipid responses to treatment with diet and statins, but the effect of HRT in different apoE genotypes is unknown. We studied the effects of HRT on the concentrations of serum lipids in apoE4-positive early postmenopausal women (genotypes 3/4 and 4/4) compared with apoE4-negative women (genotypes 2/3 and 3/3) in a population-based, prospective 5-year study. In all, 232 early postmenopausal women were randomized into 2 treatment groups: an HRT group (n=116), which received a sequential combination of 2 mg estradiol valerate (E2Val) from day 1 to 21 and 1 mg cyproterone acetate (CPA) from day 12 to 21 (Climen), and a placebo group (n=116), which received 500 mg/d calcium lactate. Serum concentrations of total, LDL, and HDL cholesterol and triglycerides were measured at baseline and after 2 and 5 years of treatment. A total of 154 women completed the final analysis. During the follow-up period, serum total cholesterol and LDL cholesterol concentrations decreased in the HRT group in apoE4-negative women (8.1% and 17.1%, respectively; P<0.001) but did not change in the HRT group in apoE4-positive women or in the placebo group. Serum HDL cholesterol concentrations decreased in the placebo group (apoE4-negative, 3.9%, P=0.015; apoE4-positive, 8.1%, P=0.004) but did not change significantly in the HRT group. Serum triglyceride levels tended to increase in both study groups and genotypes (15.1% to 36.2%, P<0.038 to 0.001), but no differences were observed between the study groups or genotypes, respectively. Our finding was that in postmenopausal Finnish women LDL cholesterol levels in apoE4-negative subjects respond more favorably to HRT than those in apoE4-positive subjects. This finding has potential importance in postmenopausal women with hypercholesterolemia, if confirmed in other studies.

Apolipoprotein E4↗

PubMed1999

Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial.

The long term effects of hormone replacement therapy (HRT) and vitamin D3 (Vit D) on bone mineral density (BMD) were studied. A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study (n = 13100) were randomized to four groups: 1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate, 2) Vit D3 (300 and 100 IU/day during the fifth year), 3) HRT and Vit D combined, and 4) placebo. Lumbar (L2-L4) and femoral neck BMD were determined by dual x-ray absorptiometry (DXA) at baseline and after 2.5 and 5 yr of treatment. Intention to treat analysis (n = 464) showed that after 5 yr, lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [+0.2% (P = 0.658) and +0.9% (P = 0.117), respectively], whereas lumbar BMD decreased by 4.6% in the Vit D group and by 4.5% in the placebo group (P < 0.001 in both). The loss of femoral neck BMD was less in the HRT (-1.4%; P = 0.005) and HRT plus Vit D (-1.3%; P = 0.003) groups than in the Vit D and placebo groups (-4.3%; P < 0.001 in both). Among those 370 women who complied with the 5-yr treatment, the effect was more pronounced: lumbar BMD had increased by 1.5% in the HRT (P = 0.009) and by 1.8% in the HRT plus Vit D group (P = 0.005), with a plateau after 2.5 yr, whereas lumbar BMD had decreased in both the Vit D and placebo groups (4.6% and 4.7%; P < 0.001, respectively). Femoral neck BMD decreased again less in the HRT (-0.4%) and HRT plus Vit D (-0.6%) groups than in the Vit D and placebo groups (-4.4% in both). This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis. The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy, nonosteoporotic, early postmenopausal women, and it confers no benefit additional to that of HRT alone.

Cholecalciferol↗

PubMed1998

Postmenopausal hormone replacement therapy and autoantibodies against oxidized LDL.

OBJECTIVES: Oxidative modification of low-density lipoprotein (oxLDL) has been suggested to play an important role in the pathogenesis of atherosclerosis, and autoantibodies against oxLDL have recently found to reflect this process. The antioxidant effect and inhibition of LDL oxidation may be one of the cardioprotective mechanisms of postmenopausal estrogen therapy. METHODS: The effects of postmenopausal hormone replacement therapy (HRT) on the concentrations of serum lipids and oxLDL autoantibodies were studied in a population-based prospective 1-year study with 64 early postmenopausal women (mean age 52.2 +/- 0.4 (S.E.M.) years). The participants were randomized into two treatment groups: HRT-group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate alone or in combination with vitamin D3, 300 IU/day + calcium lactate, 500 mg/day (n = 31) and the non-HRT-group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 300 IU/day (n = 33). The groups were well matched regarding age, body mass index and baseline serum lipid concentrations. RESULTS: The serum concentrations of total cholesterol and LDL-cholesterol decreased in the HRT-group (4.1%, P = 0.05 and 6.4%, P = 0.03, respectively, paired t-test) but did not change in the non-HRT-group. No changes in the serum concentrations of HDL-cholesterol or triglycerides were observed. Additionally, no changes in oxLDL autoantibody concentrations were observed in either group. CONCLUSIONS: Although 1-year HRT lowered serum total- and LDL-cholesterol levels, it did not influence oxLDL antibody titers. On the basis of the present results we cannot question the possibility of there being beneficial effects of HRT on the oxidative modification of LDL. However, this effect is not reflected in the levels of oxLDL autoantibodies.

Autoantibodies↗

PubMed1998

Relationships between risk factors and fractures differ by type of fracture: a population-based study of 12,192 perimenopausal women.

Relationships between selected factors and fractures according to type of fracture were retrospectively examined in 12,192 women aged 47-56 years responding to the baseline postal enquiry of the Kuopio Osteoporosis Study, Finland, in 1989. A total of 1358 women reported fractures sustained during the previous 9.4 years, i.e. at ages 38-57 years. The incidence of fractures per 1000 person-years was 17.2 after menopause and 9.5 before (p < 0.0001). The adjusted fracture risk was elevated in smokers versus non-smokers (OR = 1.5; (95% CI = 1.3-1.9) and in those with chronic health disorders versus the healthy (OR = 1.3; 95% CI 1.1-1.5). Long-term work disability was associated with fractures independently of health disorders (OR = 1.3; 95% CI 1.1-1.6). Anthropometric measures were not associated with the overall fracture risk. Menopause was strongly and linearly related to wrist fracture but not to ankle fracture. A 1 SD increase in body mass index decreased the risk of wrist fracture by 21% (p = 0.0001) but increased that of ankle fracture by 24% (p = 0.002). Smoking was related to ankle fracture (OR = 2.2; 95% CI 1.6-3.2) but not to wrist fracture (OR = 0.9; 95% CI 0.6-1.4). Health disorders were more markedly associated with fractures other than those of the wrist or ankle. Relationships between several risk factors and pre- and perimenopausal fractures vary by type of fracture. This may affect, for example, the comparability of studies with varying fracture profiles.

Adult↗

PubMed1998

Does vitamin D strengthen the increase in femoral neck BMD in osteoporotic women treated with estrogen?

The long-term effects on bone of estrogen therapy (HRT) combined with vitamin D3 supplementation were evaluated and compared with the effects of HRT without vitamin D3 supplementation in a 4-year prospective, partly randomized study among 60 osteoporotic women (mean age 55.4 years; range 49.7-59.4 years). The women studied were a subgroup of the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n = 13,100). The bone mineral densities (BMD) of the lumbar spine and femoral neck were determined by dual-energy X-ray absorptiometry (DXA) in 3236 perimenopausal women. Those 106 women with baseline BMD more than 2 SDs less than the mean value in this population, either at the lumbar spine (BMD < 0.826 g/cm2) and/or femoral neck (BMD < 0.684 g/cm2), were offered treatment for osteoporosis. After exclusions, 60 women were included in the analyses. Group allocation was: HRT (estradiol valerate (2 mg) plus cyproterone acetage, 1 mg, sequentially: ClimenR) (n = 21); HRT + Vit D: Climen + vitamin D3 (cholecalciferol, 300 IU/day, no intake during June-August) (n = 23); controls: 16 women who refused all treatment served as a non-randomized control group. In the HRT group, the highly significant increase in lumbar BMD was 5.4%, 5.3%, 4.7% and 4.0% after 1, 2, 3 and 4 years of treatment, respectively, all compared with the baseline values and with the control group. The increase in femoral neck BMD was statistically insignificant (1.4%, 2.2%, 1.9% and 2.1%, respectively; p > 0.05). In the HRT + Vit D group, the lumbar BMD increased by 3.7%, 4.9%, 4.9% and 4.9% (p < 0.001), whereas the 5.8% increase in femoral neck BMD reached significance at 4 years (p < 0.01) when compared with the control group as well as with the baseline values. However, there were no statistically significant differences in lumbar or femoral BMD changes between the two HRT groups. In conclusion, estrogen can substantially increase lumbar bone mass in patients with postmenopausal osteoporosis. In addition, the combination of HRT and vitamin D3 may increase femoral neck BMD in osteoporotic women more than estrogen alone.

Androgen Antagonists↗

PubMed1998

Effects of postmenopausal hormone replacement therapy with and without vitamin D3 on circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D3 on vitamin D metabolites (25OHD and 1,25(OH)2D) were studied in a population-based prospective 1-year study. The serum concentrations of intact parathyroid hormone (PTH), calcium, and phosphate were also studied. A total of 72 women were randomized into four treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), Vit D3 group (vitamin D3 300 IU/day + calcium lactate 500 mg/day), HRT + Vit D3 group (both above) and placebo group (calcium lactate 500 mg/day). Serum samples were taken in March-April, when vitamin D formation from sunlight in Finland is minimal after the dark winter. Serum concentrations of 25OHD increased in the Vit D3 group (33.5%, P < 0. 001) and in the HRT + Vit D3 group (38.2%, P < 0.001) but had not changed significantly in the HRT and placebo groups at the 1-year follow-up examination. Serum concentrations of calcitriol (1, 25(OH)2D) increased, however, only in the HRT group (23.7%, P < 0. 05), and remained unchanged in other groups. Serum concentrations of PTH decreased by 23.2% (P < 0.05) in the placebo group, but did not change significantly in the other three groups. The concentrations of serum calcium increased in the nonhormone groups (P < 0.001), whereas serum phosphate concentrations decreased in the hormone groups (P < 0.05 and 0.001). Our results confirm the positive effect of 1 year of HRT on serum calcitriol. Vitamin D3 supplementation increased 25OHD concentrations, but did not affect calcitriol concentrations even though the initial levels were low. Interestingly, the combination of HRT and vitamin D3 did not increase serum calcitriol concentrations as much as HRT alone.

Calcium↗

PubMed1998

The effect of nursing on the brain activity of the newborn.

OBJECTIVE: To determine whether nursing influences brain activity in the newborn and whether there are differences in this respect between breast- or bottle-feeding and pacifier sucking. STUDY DESIGN: Fifty unselected volunteer mothers and their healthy full-term infants, under care in the maternity ward after delivery, served as subjects. Thirty mother-infant pairs were studied in relation to breast-feeding and 20 to bottle-feeding and pacifier sucking. Breast-fed infants were studied between the 1st and 7th day after delivery (mean +/- 2.7 days) and the infants in the bottle-fed group between the 1st and 8th day after delivery (mean +/- 3.3 days). METHODS: Qualitative and quantitative electroencephalogram (EEG), electrooculogram, submental electromyogram, and electrocardiogram were recorded before, during and after breast- and bottle-feeding and pacifier sucking. RESULTS: The amplitude of the EEG increased significantly during breast-feeding in the posterior cortical areas in both hemispheres with a slight predominance on the right. Bottle-feeding caused a similar, but somewhat less marked change. When the breast- and bottle-fed infants were compared, a significant difference was found in only one parameter of the 84 studied. Pacifier sucking had no significant effects on EEG activity. CONCLUSION: Nursing effects a change in the brain activity of the newborn. The cortical response to nursing is most probably a result of activation of the neurohumoral mechanisms related to hunger and satisfaction, including the hypothalamic, limbic, and other brain stem structures, which also regulate the sleep-wake cycle and modulate the level of cortical activity with respect to attention and vigilance.

Bottle Feeding↗

PubMed1998

Clinical significance of alpha-catenin, collagen IV, and Ki-67 expression in epithelial ovarian cancer.

PURPOSE: To analyze alpha-catenin and collagen IV expression in epithelial ovarian cancer with special reference to their prognostic significance and correlations with clinical and pathologic characteristics, as well as cell proliferation marker Ki-67. PATIENTS AND METHODS: Alpha-catenin, collagen IV, and Ki-67 expression was immunohistochemically analyzed in paraffin-embedded specimens of 316 patients with epithelial ovarian cancer. RESULTS: Alpha-catenin and collagen IV expression was not interrelated or related to International Federation of Gynecology and Obstetrics (FIGO) stage or proliferation marker Ki-67. Alpha-catenin expression was reduced (< 100%) in 50% of primary tumors. Reduced alpha-catenin and collagen IV expression was directly related to high histologic grade (P < .001). In both univariate and multivariate analyses, Ki-67 proliferation significantly predicted overall survival. In the subset of 86 patients with stage I tumor, a reduced (< 100%) alpha-catenin expression approached statistical significance as a negative prognostic factor (P = .035) and retained its statistical significance in the multivariate analysis (P = .025). The low (< 30%) expression of alpha-catenin (n = 10) was a sign of inferior survival as compared with normal expression in both the univariate (P = .0107) and multivariate analyses (P = .0105). CONCLUSION: Alpha-catenin expression seems to be a useful marker of those FIGO stage I tumors likely to run a less favorable course. The high cell proliferative activity was associated with poor survival. In the future, alpha-catenin and Ki-67 expression should be studied in a large prospective cohort that includes early-stage cancers to select the more aggressive tumors for intense early chemotherapy.

Adolescent↗

PubMed1998

Birth weight and sex of children and the correlation to the body burden of PCDDs/PCDFs and PCBs of the mother.

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in 167 random human milk samples from urban and rural areas in Finland. Dietary habits and background information on each mother and child were gathered by questionnaire. Body mass indexes (BMI) before pregnancy and delivery in the rural area were 5-10% higher than in the urban area, but fat content of mother's milk was about 10% higher in the urban area. The mean weights of children (+/- standard deviation) were similar in the rural and urban areas among primiparae, 3,500 +/- 597 g and 3,505 +/- 454 g, respectively, although dioxin international toxic equivalents (I-TEQs) were significantly higher in the urban area. The mother's level of education did not affect the weight of the child, but concentrations of PCDDs/PCDFs (I-TEQ, 2,3,4,7,8-Cl5 dibenzofuran,1,2, 3,7,8-Cl5 dibenzodioxin) and PCBs [sum of PCBs (sumPCB), PCB-TEQ, and most PCB congeners] increased with advanced education. This is considered to be due to differences in the mother's consumption of fish. The birth weight, especially of boys, slightly decreased with increasing concentrations of I-TEQ, 2,3,4,7,8-Cl5 dibenzofuran, 1,2,3, 7,8-Cl5 dibenzodioxin, and 2,3,7,8-Cl4 dibenzodioxin; however, when the analysis was restricted to primiparae, there was no statistically significant correlation between birth weight and the concentrations of PCDDs/PCDFs. No correlation was found between the weight of the child and PCBs, PCB-TEQs, or individual PCB congeners in the whole material or among primiparae, or among boys or girls. The concentrations of PCDDs/PCDFs and PCBs inhuman milk were modeled for primiparae by weighing fish consumption, age of mother, milk fat content, and BMI before pregnancy. The linear regression resulted in values of R = 0.67 and 0.30 for the modeled dioxin I-TEQs in the urban and rural areas, respectively, and the corresponding values for sumPCBs of R = 0.60 and 0.11. The increase of PCDD/PCDF body burden was calculated to be on average 0.58 pg I-TEQ/g milk fat/year in the urban area and 0.39 pg I-TEQ/g milk fat/year in the rural area.

Adult↗

PubMed1997

Vitamin D and HRT: no benefit additional to that of HRT alone in prevention of bone loss in early postmenopausal women. A 2.5-year randomized placebo-controlled study.

The study was designed to examine the effect of hormone replacement therapy (HRT) and low-dose bone loss in non-osteoporotic early postmenopausal women and to determine whether Vit D supplementation can give additional benefit to an already optimized estrogen regimen. The effects of HRT and Vit D on bone mineral density (BMD) were studied in postmenopausal women in a 2.5-year randomized placebo-controlled study. The study population was a subgroup of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n = 13100). A total of 464 early postmenopausal women were randomized to four groups: (1) HRT (a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate (E2Val/CPA); (2) vitamin D3 (cholecalciferol, 300 IU/day); (3) HRT + Vit D; and (4) placebo (calcium lactate; 93 mg Ca2+/day). Lumbar (L1-4) and femoral neck BMD were determined by dual-energy X-ray absorptiometry before and after 2.5 years of treatment. After 2.5 years, lumbar BMD had increased by 1.8% in the HRT group (p > 0.001) and by 1.4% in the HRT + Vit D group (p = 0.002), whereas lumbar BMD had decreased by 3.5% (p < 0.001) in the Vit D group and by 3.7% (p < 0.001) in the placebo group. The loss of femoral neck BMD was lower in the HRT (-0.3%) and the HRT + Vit D (0.9%) groups compared with the Vit D (-2.4%) and the placebo groups (-3.7%). This study confirms the beneficial effect of HRT on BMD. It also shows that low-dose vitamin D supplementation has only a minor effect in the prevention of osteoporosis in non-osteoporotic early postmenopausal women and does not give any benefit additional to that of HRT alone.

Anthropometry↗

PubMed1997

PCDD, PCDF, and PCB concentrations in human milk from two areas in Finland.

Concentrations of 17 toxic 2,3,7,8-chlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and of 36 polychlorinated biphenyl congeners (PCBs) were analyzed from 167 randomly sampled human milk samples from Southern (77 samples) and Eastern (90) Finland. The level of PCDD/Fs and PCBs in human milk in Southern Finland was about 25% higher than those from Eastern Finland. The level of PCDD/Fs in human milk in Finland was the same as in Sweden, 30-50% lower than in milk from Central Europe but about 45% higher than values from Norway or Russia. The PCB concentrations in Southern Finland were at the same level as in the Netherlands, and in Eastern Finland at the same level as in Norway. The levels of PCDD/Fs and PCBs decreased with increasing number of children: the third child was exposed to about 70% of the amount of PCDD/Fs and PCBs as compared with the first child, and the eighth to tenth child to about 20%. The congener patterns of PCDD/Fs and PCBs in Finnish human milk were similar to the countries of Central Europe, however, the levels of penta- and heptachlorinated furans were slightly higher than in milk from other countries.

Benzofurans↗

PubMed1997

Lactose intolerance associated with fractures of weight-bearing bones in Finnish women aged 38-57 years.

Lactose intolerance (LI) often results in decreased calcium intake. To test if long-term low intake of calcium affects bone strength, we examined fracture risks related to LI in women aged 38-57 years. The 11,619 Finnish women aged 47-56 years who responded to the baseline postal inquiry of the Kuopio Osteoporosis Risk Factor and Prevention Study in 1989 formed the study population. In all, 896 women reported LI and 1299 women reported a fracture in 1980-1989. Current intake of dairy calcium was lower in women with LI (570 mg/d) than in the other women (850 mg/d) (p < 0.0001). The fracture risk in general was slightly elevated in women with LI compared with the other women, with an odds ratio (OR) (95% CI) of 1.33 (1.09-1.62). However, the fractures at the three most common sites (wrist, ankle, and rib) were not related to LI. In contrast, fractures at the tibia and metatarsal were strongly related to LI with ORs of 3.31 (1.51-7.24) and 2.84 (1.47-5.50), respectively. The adjusted OR for nonankle lower body fractures combined was 2.15 (1.53-3.04), whereas that for all upper body fractures combined was 1.15 (0.88-1.54). The 10 women with LI and a tibial or metatarsal fracture showed a 19% lower femoral BMD than all the other women in the densitometry subsample of 3222 women (p < 0.001). Long-term premenopausal calcium deficiency differentially affects bones with weight-bearing nonankle bones being at the greatest risk of suffering reduced strength.

Adult↗

PubMed1997

Amniotic fluid U. urealyticum colonization: significance for maternal peripartal infections at term.

The aim of this study was to examine the relationship between maternal peripartal infectious morbidity and amniotic fluid colonization by U. urealyticum. Amniotic fluid specimens for bacterial and mycoplasmal cultures were obtained by aspiration at nonelective cesarean section from 98 pregnant women. Amniotic fluid cultures revealed micro-organisms in 70 (71%) parturients and U. urealyticum was the most frequently isolated species, detected in the specimens from 38 (39%) women. In the total study population, the prevalence of clinically defined infectious morbidity was 26%, including 8 (8%) patients with chorioamnionitis, 11 (11%) with endometritis, 5 (5%) with urinary tract infection, and 4 (4%) with wound infection. A significant association between the amniotic fluid U. urealyticum colonization and increased maternal peripartal infectious morbidity was observed (p < 0.0027; relative risk 4.1; 95% confidence limits 1.6 to 10.7). Amniotic fluids positive for U. urealyticum were significantly more often positive for other potentially pathogenic bacteria (p < 0.0024) and particularly for Bacteroides spp. (p < 0.0074). Our results support the existence of an association between amniotic fluid U. urealyticum invasion and maternal infectious morbidity. However, U. urealyticum was not usually isolated alone from amniotic fluids but combined with other pathogenic bacteria, the severity of infections were not enhanced when U. urealyticum was present and parturients with diagnosed infections managed well without specific antibiotic against U. urealyticum. Hence, it appears that the significance of U. urealyticum in maternal infections in this study population was mainly based on its interactions with other bacteria.

Adult↗

PubMed1997

Expression of CYP1B1 in human adult and fetal tissues and differential inducibility of CYP1B1 and CYP1A1 by Ah receptor ligands in human placenta and cultured cells.

Expression of the Ah receptor-regulated cytochrome P4501B1 (CYP1B1) gene was studied in human adult and fetal tissues and cells in culture by reverse transcriptase-coupled polymerase chain reaction (RT-PCR). In adults, CYP1B1 mRNA was detected in liver, lymphocytes, cells of bronchoalveolar lavage samples and uterine endometrium, but not in lung. The level of expression was very low in adult liver and only three out of six fetal livers expressed CYP1B1. Extrahepatic fetal tissues, especially brains and kidneys, expressed high levels of CYP1B1. CYP1B1 mRNA was constitutively detected at a low level in first trimester and full-term placental samples. A competitive RT-PCR assay was developed to assess the regulation of CYP1B1. CYP1B1 mRNA was not induced in placenta by maternal cigarette smoking. Inducibility of CYP1B1 in cells in culture by the Ah receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin was studied in primary fibroblasts and chorion carcinoma cell line JEG-3 having different CYP1A1 induction properties. Inducibility of CYP1B1 was found to be regulated independently from CYP1A1. In JEG-3 cells CYP1A1 mRNA was induced up to 9000-fold, while the expression of CYP1B1 was not affected. Expression of Ah receptor and Ah receptor nuclear translocator (regulators of the CYP1 family) was determined in human placenta and in the JEG-3 cell line. Expression of these transcription factors was found neither to be co-regulated nor affected by Ah receptor ligands. This study provides evidence that in addition to the Ah receptor complex, other cell-specific factors modulate the response of CYP1B1 and CYP1A1 to Ah receptor ligands.

Adult↗

PubMed1997

Biochemical bone markers and bone mineral density during postmenopausal hormone replacement therapy with and without vitamin D3: a prospective, controlled, randomized study.

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D on the serum concentrations of three bone biochemical markers and their associations with bone mineral density (BMD) were studied in a population-based 1-yr follow-up study. A total of 72 healthy postmenopausal women were randomized into 4 treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), D group (vitamin D3, 300 IU/day), HRT+D group (both of the above), and placebo group (calcium lactate, 500 mg/day). Serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as biochemical markers of bone formation, and serum type I collagen carboxy-terminal telopeptide was measured as a marker of bone resorption at baseline and after 6 and 12 months of treatment. To investigate the associations of these markers with BMD, lumbar (L2-L4) and femoral neck BMDs were determined by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment. In both hormone groups, the serum concentrations of the three bone metabolic markers had decreased after 12 months. Those of OC decreased by 29.2% (P = 0.017) in the HRT group and by 37.3% (P = 0.004) in the HRT+D group, and BAP concentrations decreased by 34.4% (P < 0.001) in the HRT group and by 36.2% (P < 0.001) in the HRT+D group. Serum type I collagen carboxy-terminal telopeptide concentrations had decreased by 21.6% (P = 0.012) in HRT group and by 14.1% (P = 0.011) in the HRT+D group. In the D group, the serum concentrations of BAP had decreased by 11.7% (P = 0.040) after 12 months, but the other two markers showed no change. The only change seen in the placebo group was a 19.2% increase in OC concentrations (P = 0.041) after 6 months, but at 12 months, the mean OC level was similar to that at baseline. After 2.5 yr, both lumbar and femoral BMD had decreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019), respectively] and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010), respectively], whereas no significant changes occurred in the hormone groups. There were significant inverse correlations between the changes in lumbar and femoral BMDs and changes in all three biochemical markers (r = -0.240 through -0.336; P = 0.005-0.064). Our results suggest that HRT counteracts the biochemical changes caused by increased bone turnover associated with menopause. Importantly, the changes in bone markers correlate with long term changes in BMDs of lumbar spine and femoral neck. Low dose vitamin D treatment, however, seems to have only marginal effects on bone metabolism in early postmenopausal healthy women.

Alkaline Phosphatase↗

PubMed1997

Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy.

OBJECTIVE: The positive short-term effects of postmenopausal hormone replacement therapy (HRT) on serum lipids are well known, but it has been suggested that they vanish with time. Cholecalciferol (vitamin D3) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D3 on serum lipids is poorly known. The long-term effects of HRT and vitamin D3 on the concentrations of serum lipids were studied in a population-based prospective 3-year study. DESIGN AND METHODS: 464 women were randomized into four treatment groups: (i) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), (ii) Vit D3 (vitamin D3 300 IU/day), (iii) HRT+Vit D3 (both as above), (iv) placebo (calcium lactate 500 mg/day). RESULTS: 320 women completed the study. After three years of treatment, serum concentrations of low density lipoprotein (LDL) cholesterol decreased in the HRT group (10.1%, P<0.001) and the HRT+Vit D3 group (5.9%, P=0.005), increased in the Vit D3 group (4.1%, P=0.035) but remained unchanged in the placebo group. The concentrations of total cholesterol decreased by 5.8% in the HRT group (P<0.001) and by 3.3% in the HRT+Vit D3 group (P=0.023), but did not change in the other two groups. Serum concentrations of high density lipoprotein (HDL) cholesterol decreased in the Vit D3 group (5.2%, P=0.001), HRT+Vit D3 group (3.7%, P=0.046), and the placebo group (4.5%, P=0.006) but did not change significantly in the HRT group. The HDL/LDL ratio increased in the HRT group (10.5%, P=0.006) and decreased in the Vit D3 group (10.5%, P<0.001) whereas no changes occurred in the other two groups. In addition, serum triglycerides increased similarly in all groups (14.0-18.8%, P<0.05-0.001). CONCLUSIONS: Our results confirm the positive long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin D3 treatment was associated with increased serum LDL cholesterol. Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D3. However, the relevance of these associations to cardiovascular morbidity remains to be established.

Analysis of Variance↗

PubMed1997

C-reactive protein in uncomplicated parturients delivered by cesarean section.

BACKGROUND: The purpose of this study was to determine normal values and evaluate clinical variables associated with postoperative C-reactive protein serum concentration after uncomplicated abdominal delivery. METHODS: C-reactive protein serum concentrations were determined serially by a quantitative immunoturbidimetric assay in 479 clinically non-infected parturients undergoing uncomplicated Cesarean section, before operation and during the first week of puerperium. Associations between clinical variables and maximal postoperative C-reactive protein levels were examined by variance analysis. RESULTS: The preoperative values were significantly higher in parturients from whom samples were obtained after the onset of labor and/or rupture of the membranes (16 +/- 10 (s.d.) mg/l) compared with the preoperative values obtained from parturients operated with no labor and intact membranes (12 +/- 7 (s.d.) mg/l) (p < 0.0001). An overall significant increase was observed in C-reactive protein concentrations after delivery, peaking on the second postoperative day, compared with the preoperative values. In the parturients operated upon after the onset of labor or ruptured membranes, postoperative values were 24% higher up to the sixth postoperative day than in parturients operated upon with intact membranes and no labor. The onset of labor, duration of operation, the number of vaginal examinations and the duration of internal monitoring before operation were associated with the maximal postoperative C-reactive protein concentrations, but they explained only 9% of postoperative CRP level variation. CONCLUSIONS: The wide range of serum C-reactive protein concentrations during puerperium complicates its use as a simple marker in obstetric postoperative complications. However, after normal uncomplicated operative delivery, C-reactive protein concentrations rapidly decrease towards the baseline after the second to third postoperative day.

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