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Biomedical subjects

M Parviainen

Publications and source records attributed to M Parviainen.

At least 19 recordsLinked to original sources

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

[HIV screening in maternity clinics].

With a decision of the Finnish Department of Health and Social Welfare the HIV-screenings have been extended from the beginning of the year. The most important reason for this is the development of the medical treatment. With the present treatment, the transmitting of the HIV-infection from mother to child can be prevented in most cases.

AIDS Serodiagnosis

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

Hen egg yolk antibodies purified by antigen affinity under highly alkaline conditions provide new tools for diagnostics. Human intact parathyrin as a model antigen.

Hen egg yolks have been recognized as convenient source for specific antibodies, although their utility in diagnostic applications has been hampered by the lack of efficient purification methods. In the present study, anti-human parathyrin antibodies were raised in rabbits, hens and mice using synthetic human parathyrin peptide (1-84) as an antigen. The antibodies were affinity purified with amino- (1-30) and carboxy- (49-89) terminal peptides of parathyrin under highly alkaline elution conditions, and were evaluated for their diagnostic value in different combinations in immunoenzymometric assay (IEMA) format. A pair of hen egg yolk antibodies were subjected to further methodological validation in the IEMA that was constructed with the N-terminal capture and C-terminal detection antibodies. The synthetic intact human parathyrin (1-84) peptide served as a standard. This within-day IEMA procedure turned out to be sensitive and it correlated well with the two independent intact parathyrin immunoradiometric assays. As shown in the present study, the immuno affinity purification with the highly alkaline elution conditions provides an efficient method for utilization of hen egg yolk antibodies. This is the first report on an application making use of a combination of two hen egg yolk antibody preparations in measuring a homogeneous protein in human serum.

Animals

Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland).

Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n = 34) and with breast cancer (n = 32). In postmenopausal women, lower dietary intake (P = 0.006) and a smaller concentration of vitamin E in breast adipose tissue (P = 0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r = 0.25, P = 0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.

Adipose Tissue

Evolution, risk factors, and prognostic implications of albuminuria in NIDDM.

OBJECTIVE: To study the cumulative incidence of albuminuria and its determinants in NIDDM patients and nondiabetic subjects from the diagnosis and impact of albuminuria on cardiovascular mortality. RESEARCH DESIGN AND METHODS: We performed a 10-year prospective observational study of 133 well-characterized middle-aged patients with newly diagnosed NIDDM and 144 control subjects. Both groups were examined at baseline and after 5 and 10 years. Urinary albumin excretion was determined from timed 24-h (baseline and 5-year examinations) or overnight samples (10-year examination). Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/24 hr or 20-200 micrograms/min, with the higher values considered as macroalbuminuria. RESULTS: The cumulative incidence of micro- and macroalbuminuria increased sharply after 5 years in NIDDM patients (baseline: 18.2 and 3.0%; 5 years: 18.9 and 1.8%; and 10 years: 33.0 and 10.2%) but markedly less in control subjects (baseline: 1.4 and 0%, P < 0.001 for diabetic patients vs. control subjects for any albuminuria; 5 years: 6.0 and 0.8%, P < 0.01; 10 years: 11.9 and 0.8%, P < 0.001). The most important determinant of the development of albuminuria was the metabolic control of diabetes in NIDDM patients during the follow-up, whereas in nondiabetic subjects, the development of albuminuria was related to elevated blood pressure and fasting insulin levels. Baseline and 5-year albuminuria predicted subsequent cardiovascular mortality in diabetic patients, even when adjusted for multiple risk factors. The risk of cardiovascular death in NIDDM patients increased by simultaneous occurrence of hyperinsulinemia and albuminuria. CONCLUSIONS: The frequency of microalbuminuria in patients with NIDDM increases sharply with the duration of diabetes. Chronic hyperglycemia is the main risk factor for microalbuminuria in diabetic patients. Microalbuminuria accompanied by hyperinsulinemia is a powerful predictor of cardiovascular death in NIDDM patients.

Age Factors

Analysis of low-dose benzodiazepines by HPLC with automated solid-phase extraction.

We describe a simple, specific, and sensitive reversed-phase HPLC method with automated solid-phase extraction (SPE) for analyzing alprazolam, clonazepam, and nitrazepam concentrations in human serum or plasma. We prepare samples and calibrators with an automated sample preparer, using 100-mg Bond-Elut C18 SPE columns. The HPLC method uses isocratic elution with acetonitrile:methanol:dipotassium hydrogen phosphate, 10 nmol/L, pH 3.7 (30:2:100 by vol), at a flow rate of 1.5 mL/min to separate the drugs. We detect the benzodiazepines with diode-array detector at 240 nm; analyses of peak purity are performed at 210-365 nm. The recoveries were between 94% and 100%. The intraassay and interassay CVs were between 1.0% and 4.1%. The detection limit is 5 nmol/L. The antiepileptic and antidepressant drugs tested did not interfere with the assay. We developed the method for use in a clinical laboratory for therapeutic drug monitoring.

Alprazolam

Smoking cessation and nicotine substitution modulate eicosanoid synthesis ex vivo in man.

The effects of smoking cessation with and without nicotine substitution on prostaglandin E2, leukotriene B4, leukotriene E4, and thromboxane B2 synthesis ex vivo in man were investigated. Blood samples were obtained from 20 healthy non-smoking controls and from 30 healthy smoking volunteers before and 3, 7 and 14 days after smoking cessation. Half of the smokers used nicotine chewing gum as a substitution therapy. Urinary cotinine and trans-3'-hydroxycotinine as well as thiocyanate excretions were used as indicators for the use of nicotine chewing gum and smoking, respectively. Prostaglandin E2, leukotriene E4, and thromboxane B2 were measured from whole blood after calcium ionophore A23187 stimulation by direct radioimmunoassay and leukotriene B4 by RP-HPLC. Prostaglandin E2 and thromboxane B2 syntheses were about three times and leukotriene B4 and E4 syntheses four times higher in smokers than in controls. Three days after smoking cessation without nicotine substitution, levels were lowered significantly to about 70%, 80%, 45% and 60% of the initial values; and after 14 days to 55%, 80%, 45% and 50%, respectively. In the nicotine substitution group no significant decreases were seen during the two-week follow-up. The increased level of eicosanoid synthesis detected in smokers in this ex vivo study may contribute to the harmful cardiovascular effects of smoking. Long-term nicotine substitution might diminish the beneficial effects of smoking cessation due to the possible stimulatory effects of nicotine and cotinine on eicosanoid synthesis even in vivo.

Adult