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Biomedical subjects

M Parviainen

Publications and source records attributed to M Parviainen.

At least 37 records · Page 2Linked to original sources

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↗

Metabolic stress modifies the thermogenic effect of dobutamine in man.

OBJECTIVE: To study if metabolic stress modifies the thermogenic effect of dobutamine. DESIGN: Prospective, increasing dose, pharmacologic study. SETTING: Laboratory of the Department of Intensive Care Unit at a university hospital. SUBJECTS: Twelve normal volunteers. INTERVENTIONS: Dobutamine hydrochloride was infused to 12 healthy male volunteers starting at a dose of 2 micrograms/min/kg and gradually increased to 4 and 6 micrograms/min/kg. Each dose of dobutamine was infused for 20 mins. Metabolic stress was induced in six of the 12 volunteers using a triple hormone infusion (epinephrine, cortisol, and glucagon) before dobutamine, and was continued at a constant rate during the dobutamine infusion. The remaining six volunteers served as the control group and received only dobutamine. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) was measured using a metabolic monitor. Arterial blood pressure was measured noninvasively, and cardiac output was monitored by Doppler echocardiography. Plasma concentrations of dopamine, norepinephrine, and epinephrine were measured in both groups. In the triple hormone group, blood was sampled to measure concentrations of insulin, glucagon, cortisol, free fatty acids, and glycerol to ensure the presence of a metabolic stress reaction. At the maximum dose, dobutamine induced a 19% increase (from 140 +/- 17 to 166 +/- 17 mL/min/m2) in VO2 in the control group and an 11% increase (from 167 +/- 10 to 184 +/- 13 mL/min/m2) in the triple hormone group (p < .05 between the two groups) compared with baseline. No change in the respiratory exchange ratio was seen. The triple hormone infusion alone induced hypermetabolism, a marked hemodynamic response, and increased lipolysis. CONCLUSIONS: Stress, induced by a triple hormone infusion, diminishes the thermogenic effect of dobutamine. In the clinical setting, a > 10% to 15% increase in VO2 in response to dobutamine may not be explained just by the thermogenic effect of the drug.

Adult↗

Two-site enzyme immunoassay for measuring intact human osteocalcin in serum.

We developed a sensitive two-site sandwich ELISA for quantitative analysis of human osteocalcin in serum or plasma. Our method is based on two different highly specific antibodies recognizing epitopes at different ends of the protein so that only intact osteocalcin is detected. The method is fast (total analysis time less than 6 h/96 wells), precise (intraassay variation less than 2.3% at four different levels; n = 10, and interassay variation less than 2.5%, n = 5, respectively), and accurate, with a mean recovery of 105%. The detection limit in serum is approximately 0.1 micrograms/liter. The mean concentration of osteocalcin in normal serum with this assay is 3.3 micrograms/liter (SD 3.7 micrograms/liter; range 0.1-13.1 micrograms/liter; n = 41), and the reference range is 0.28-10.1 micrograms/liter (10 and 90% confidence limits). The method shows a reasonable positive linear correlation with other osteocalcin assays (Incstar, r = 0.55, p < 0.05, n = 13; Henning Oscatest, r = 0.52, p < 0.005, n = 34). A good correlation (r = 0.70, p < 0.001) between individual osteocalcin and bone-specific alkaline phosphatase serum concentrations was observed in normal subjects. We found a low or undetectable concentration of intact osteocalcin in serum of all four of our patients with acute primary hyperparathyroidism, and in all five patients with hypocalcemic secondary hyperparathyroidism, which suggests that PTH effectively inhibited the synthesis of osteocalcin in osteoblasts. The serum concentration of intact osteocalcin was elevated in two of three patients with chronic primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Production of monoclonal and polyclonal antibodies against human osteocalcin sequences and development of a two-site ELISA for intact human osteocalcin.

In this study we have raised polyclonal and monoclonal antibodies against human osteocalcin sequences coupled to bovine serum albumin (BSA). The antibodies were used for the development of a novel two-site ELISA on microtiter plates for intact human osteocalcin. The epitope, recognized by the monoclonal hybridoma product Os 31/2 that was used as the capture antibody, was located on the amino terminal sequence 1-29. The antibodies used for detection recognized the sequence 1-49. This method failed to detect any tryptic peptides derived from human osteocalcin sequence 1-49 nor did it detect peptide 1-29, thus demonstrating high specificity for the intact osteocalcin 1-49 only. This is a novel technique for the determination of intact osteocalcin. We have also validated the assay parameters for routine use. This direct and relatively simple procedure promises to be a powerful diagnostic and investigative tool.

Adult↗

Effects of aerobic long distance running training (up to 40 km.day-1) of 1-year duration on blood and endocrine parameters of female beagle dogs.

The effects of long distance running training on blood parameters, hormone responses and bone growth were studied in young growing dogs. A genetically uniform group of female beagles matched with respect to age and body mass were used. The runner dogs (n = 10) underwent gradually increased running exercise up to 40 km.day-1 on a treadmill with 15 degrees uphill gradient 5 days each week during a period of 1 year, while the littermate control dogs (n = 10) were kept in their cages throughout the study. Low plasma lactate concentrations of the runners measured immediately after the running training indicated the aerobic metabolism of the dogs while running. Significant decreases of blood haemoglobin concentrations (11%), blood erythrocyte number (10%), and erythrocyte packed cell volume (12%) were found in the runner group. Throughout the experiment, the value of thyroxine was slightly lower (13%) in the runners but no changes were found in tri-iodothyronine, free thyroxine, or cortisol serum concentrations. Serum oestradiol concentration at 56 weeks was significantly lower (42%) in the runner group than in the control group but was not as low (27%) at 70 weeks. Somatomedin-C concentration had decreased significantly by 37% at the age of 56 weeks in the runner group but was again at the level of the control dogs at the end of experiment (at 70 weeks). Ulna and radius bone mass as a ratio to the body mass had significantly increased in the runners. It would seem from our study that long distance running has a positive effect on bone growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of two low-fat diets, high and low in polyunsaturated fatty acids, on plasma lipid peroxides and serum vitamin E levels in free-living hypercholesterolaemic men.

Diet enriched with polyunsaturated fat may increase the susceptibility of LDL to oxidation. Therefore the effects of two low-fat diets on plasma lipid peroxides in free-living mildly hypercholesterolaemic men (n = 37) were investigated in a randomized single-blind 28-week study. Composition of the diets were (1) American Heart Association (AHA) type 32/10:8:8 (indicating percentages of energy from total fat/saturated fat:monoenes:polyenes in actual diet); (2) low-fat 30/12:8:3. The subjects kept 3-day dietary records five times during the study to estimate the intake of nutrients. Plasma lipid peroxides were measured photometrically as the thiobarbituric-acid reactive substances (TBARS). Levels of serum vitamin E during the study were also determined. Mean change (+/- SD) in serum low density lipoprotein (LDL) cholesterol was similar in both groups (-0.32 +/- 0.76 vs -0.32 +/- 0.87 mmol/l) (AHA type vs low-fat). Level of TBARS decreased (P < 0.05) during the AHA type diet (-8.4 +/- 37.1%) (mean +/- SD) and increased (P = 0.228) during the low-fat diet (+8.7 +/- 27.0%) from 0 to 6 months. The mean intake of total active tocopherols was greater (14.7 +/- 3.7 mg) during the AHA type diet compared to the low-fat diet (7.8 +/- 2.1 mg). Serum vitamin E to LDL cholesterol ratio increased from 8.9 +/- 2.9 to 9.6 +/- 2.4 nmol/mmol (0 vs 6 months) (P = 0.07) during the AHA type diet and from 8.6 +/- 2.6 to 9.3 +/- 2.4 nmol/mmol (P = 0.159) during the low-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)

American Heart Association↗

Endurance training associated with slightly lowered serum estradiol levels decreases mineral density of canine skeleton.

The effects of long-term running exercise were studied in 20 beagle dogs. A total of 10 dogs ran from the age of 15 weeks to the age of 70 weeks in a progressive program for up to 40 km/day. A total of 10 sister dogs spent the study period in individual cages. When the dogs were 70 weeks old, bone mineral density of the vertebrae, hip, and radius was analyzed by dual-energy x-ray absorptiometry (DEXA; Lunar) and the vertebrae were also assessed by quantitative computed tomography (QCT; Siemens DR 1). Mineral density was lower in the running dogs than in the controls. The difference was greatest in the spine in the QCT analysis. Blood chemistry analyses revealed that the metabolism of the bone was significantly accelerated. The estradiol levels showed the trend to be reduced in the running group. The beneficial effect of exercise on mineral density has been shown in many earlier studies. However, in this study we demonstrate the possibility of adverse effects of long-term exercise on bone tissue. The change was associated with a decrease of serum estradiol level.

Alkaline Phosphatase↗

Absorption of ascorbic acid from a film-coated tablet and from a new enteric-coated pellet preparation in subjects with inadequate plasma levels of ascorbic acid.

The effects of a film-coated tablet and a novel enteric-coated pellet preparation of ascorbic acid (CAS 50-81-7) on the plasma concentration and on the urinary excretion of ascorbic acid were investigated. The pharmacokinetic properties of these dosage forms were also compared both after a single dose and in steady state. The study was carried out as a randomized, single blind parallel group trial in 11 volunteers with inadequate plasma levels of ascorbic acid. The duration of the treatment period was 7 days. After the first dose, higher plasma ascorbic acid concentration as well as AUC and Cmax values were achieved with the film-coated preparation. After the multiple dosing in steady state, plasma ascorbic acid concentration as well as AUC and Cmax values were higher with the new pellet preparation. In addition, the plasma ascorbic acid concentration remained on higher level with pellet preparation on the 7th day. Tmax values for the pellet preparation were also slightly higher on both of the pharmacokinetic test days. The amount of ascorbic acid excreted in urine was higher with the film-coated tablet. According to the results of this study it can be supposed that during the long-term supplementation the more complete absorption can be achieved with the new enteric-coated pellet preparation.

Adult↗

Combination therapy with lovastatin and guar gum versus lovastatin and cholestyramine in treatment of hypercholesterolemia.

Sixty-two patients (34 men and 28 women) aged 19-64 years, half of whom had familial hypercholesterolemia, treated initially for 18 weeks with lovastatin alone were randomly allocated either to lovastatin (L) and cholestyramine (16 g/day) or lovastatin and guar gum (L + GG 20 g/day) treatment for 18 additional weeks to compare the hypocholesterolemic effects of these two combination therapies. The patients were selected for this study from a larger study of patients (n = 120) with severe hypercholesterolemia [serum total cholesterol (serum Chol) 6.5-16.3 mM before treatment], and only those patients in whom serum Chol after lovastatin alone (dose 80 mg/day) remained greater than or equal to 5.2 mM were eligible for evaluation of combination therapies. Serum Chol decreased from 10.6 +/- 1.6 to 5.9 +/- 1.3 mM (mean +/- SD) (p less than 0.001) and low-density lipoprotein cholesterol (LDL Chol) from 8.5 +/- 1.8 to 4.1 +/- 1 mM (p less than 0.001) in patients treated with L + GG (values before the beginning of lovastatin and at the end of the combination therapy). The respective changes were from 10.9 +/- 2.2 to 5.5 +/- 1.2 mM (p less than 0.001) and from 8.7 +/- 2.3 to 3.5 +/- 1.2 mM (p less than 0.001) in patients treated with lovastatin and cholestyramine (L + C). At the end of the study, both serum Chol (p less than 0.005) and LDL Chol (p less than 0.01) were significantly lower with L + C than with L + GG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The necessity and safety of calcium and vitamin D in the elderly.

The necessity and safety of an oral calcium (Ca) and vitamin D regimen was evaluated in a population of 66 independently living and 73 institutionalized elderly women over an 11-week winter period. The members of both groups were randomly assigned into trial and control groups. Serum Ca, creatinine, and calcidiol levels were measured before and after the trial. The regimen consisted of 1.558 g of Ca and 45 micrograms (equal to 1,800 IU) of vitamin D administered daily in addition to the normal diet. The controls received no treatment. A majority of the elderly subjects living independently had ensured their Ca, and a quarter of them also their vitamin D intake on their own initiative. The mean serum calcidiol concentration before the trial was 24.1 nmol/L in the institutionalized and 38.5 nmol/L in the elderly subjects living independently (P less than .001). After the trial, serum calcidiol was 10.4 nmol/L in the institutionalized control subjects and had decreased (P less than .001) in both control groups, but increased (P less than .001) in both treatment groups. The safety indicators, serum Ca, creatinine, and calcidiol, did not indicate any group or individual side effect.

Aged↗

Lymphocyte beta-2-adrenoceptors and plasma catecholamines in fetal hypoxia.

Conclusive evidence has been furnished that the beta 2-adrenoceptor density in circulating lymphocytes is related to that of beta 2-adrenoceptors in tissues from the same subjects. This study was designed to evaluate the effect of fetal hypoxia on lymphocyte beta 2-adrenoceptor density. The material consisted of 8 hypoxic newborns, 4 delivered by vacuum extraction and 4 by Caesarean section, after approximately 10 h parturition. The control group consisted of 8 vaginally delivered newborns without hypoxia. Umbilical plasma adrenaline and noradrenaline were significantly elevated in the hypoxic newborns. Their lymphocyte beta 2-adrenoceptor density was lower (p less than 0.01) than that in the controls. A plausible explanation for this finding might be downregulation of beta 2-adrenoceptors because of elevated plasma catecholamine level.

Down-Regulation↗