Biomedical subjects

K Laitinen

Publications and source records attributed to K Laitinen.

At least 19 recordsLinked to original sources

PubMed2006

Impact of national fortification of fluid milks and margarines with vitamin D on dietary intake and serum 25-hydroxyvitamin D concentration in 4-year-old children.

OBJECTIVE: To assess the impact of national fortification of fluid milks and margarines with vitamin D on dietary intake and on serum 25-hydroxyvitamin D concentration in Finnish 4-year-old children. DESIGN, SUBJECTS AND METHODS: Two cohorts of children were studied during wintertime, one before (n=82) in 2001-2002 and the other after (n=36) the initiation of fortification in 2003-2004. Dietary intake was estimated by 4-day food records and serum 25-hydroxyvitamin D concentration was analyzed by radioimmunoassay. RESULTS: The mean intake of vitamin D was higher the after initiation of fortification (mean (95% confidence interval (CI)); 4.5 (3.8-5.1) microg) than before it (2.1 (95% CI 1.8-2.3) microg; P<0.001), although there were no differences in consumption of the main food sources of vitamin D between the two cohorts. The difference between the cohorts was also evident when the intake of vitamin D was adjusted for energy intake (0.78 (95% CI 0.70-0.90) and 0.37 (95% CI 0.32-0.42) microg/MJ after and before fortification, respectively, P<0.001). After fortification, the mean intake approached that recommended, but was achieved by only 30.6% of the children. Equally, the serum 25-hydroxyvitamin D concentration was higher after fortification (64.9 (95% CI 59.7-70.1) nmol/l) compared to prior it (54.7 (95% CI 51.0-58.4) nmol/l; P=0.002). CONCLUSIONS: The results indicate that the national fortification of fluid milks and margarines with vitamin D safely improved the vitamin D status of children. This approach, in view of the novel health effects beyond bone metabolism, encourages fortification of new food sources with vitamin D or use of vitamin D supplements particularly during wintertime.

Animals↗

PubMed2006

Impact of dietary counselling on nutrient intake during pregnancy: a prospective cohort study.

The aim of this study was to assess the impact of dietary counselling combined with the provision of food products on food and nutrient intake in pregnant women. We carried out a prospective cohort study of healthy and atopic pregnant women (n 209), who were randomized into dietary intervention and control groups. The intervention group received dietary counselling and food products to modify the fat composition of their diet to meet current recommendations. Three-day food records were collected during each trimester of pregnancy. Women in the intervention group consumed more vegetables, fruits, soft margarines and vegetable oils and less butter than those in the control group during the course of pregnancy (P<0.05). The main distinction between the groups in nutrient intake over the pregnancy was attributable to a higher energy intake (% energy) of PUFA by 0.5%energy (95% CI 0.1, 0.8) and to a lower intake of SFA by 0.8 % energy (95% CI -1.4, -0.4) in the intervention group. Dietary intake of vitamin E was 1.4 mg (95% CI 0.6, 2.2), folate 20.9 microg (95% CI 0.8, 41.0) and ascorbic acid 19.8 mg (95 % CI 3.5, 36.0) higher in the intervention group compared to the controls, while no differences in other nutrients were detected. Dietary counselling combined with the provision of food products during pregnancy is of importance in modifying food and nutrient intake, with potential health benefits.

Adult↗

PubMed2006

Serum, cheek cell and breast milk fatty acid compositions in infants with atopic and non-atopic eczema.

BACKGROUND: The major theory implicating diet with allergic diseases is associated with altered food consumption and subsequent changes in fatty acid composition. OBJECTIVE: To investigate fatty acid compositions among infants with atopic and non-atopic eczema and healthy infants and to evaluate the expediency of non-invasive cheek cell phospholipid fatty acid composition as a marker in patients with eczema. METHODS: Diagnosis of eczema in infants was confirmed clinically and by positive (atopic eczema, n=6) or negative (non-atopic eczema, n=6) skin prick testing in comparison with controls (n=19). The fatty acid compositions of infant cheek cell and serum phospholipids and breast milk total lipids were analysed by gas chromatography. RESULTS: The distinction between atopic and non-atopic eczema was manifested in cheek cell phospholipids as linoleic acid (14.69 (13.67-15.53)% of total fatty acids; the median (interquartile range)), the sum of n-6 fatty acids (19.94 (19.06-20.53)%) and the sum of polyunsaturated fatty acids (22.70 (21.31-23.28)%) were higher in infants with atopic eczema compared with non-atopic eczema (12.69 (10.87-13.93); 17.72 (15.63-18.91) and 19.90 (17.64-21.06), respectively; P<0.05) and controls (12.50 (12.16-13.42); 18.19 (17.43-18.70) and 20.32 (19.32-21.03), respectively; P<0.05). Serum phospholipid gamma-linolenic acid was lower in both atopic and non-atopic eczema compared with controls (P<0.05) and additionally eicosapentaenoic acid was higher in atopic eczema compared with controls (P<0.05). CONCLUSION: These preliminary results suggest differences in fatty acid compositions between the two types of eczema, calling for further evaluation in a larger setting. The two types of eczema may be regulated by different immunological processes, and fatty acids may have a more profound role in the atopic type.

Case-Control Studies↗

PubMed2005

Serum osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) concentrations in allogeneic stem cell transplant-recipients: a role in bone loss?

PURPOSE: Osteoporosis is a long-term complication of allogeneic stem cell transplantation (SCT). Receptor activator of nuclear factor-kappaB ligand (RANKL) increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A deficiency of OPG or an excess of RANKL may contribute to post-SCT bone loss. METHODS: Serum OPG and soluble RANKL (sRANKL) concentrations were determined in 30 patients who received calcium, vitamin D and sex steroids--with or without pamidronate--prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to those in healthy controls. RESULTS: Despite all treatments patients lost bone at the hip. At baseline, serum OPG was similar in patients and controls; in the two patient groups it increased by 26-27% at 6 months post-SCT (p=0.002-0.028) and over the control level (p=0.002). Serum sRANKL concentrations were also similar in patients and controls at baseline. In those patients receiving pamidronate sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in 28 additional patients who did not receive pamidronate, at a median of 122 days after SCT. In this latter group, OPG but not sRANKL concentrations were clearly elevated (p<0.001) in comparison to healthy controls. In conclusion, the present study fails to support the view that an excess of sRANKL or a deficiency of OPG would have a substantial impact on bone loss in SCT-recipients. CONCLUSION: Serum sRANKL concentrations may be modulated by bisphosphonates.

Absorptiometry, Photon↗

PubMed2004

Serum tartrate-resistant acid phosphatase 5b in monitoring bisphosphonate treatment with clodronate: a comparison with urinary N-terminal telopeptide of type I collagen and serum type I procollagen amino-terminal propeptide.

Osteoclastic tartrate-resistant acid phosphatase activity in serum (S-TRACP 5b) was measured in postmenopausal women ( n =59, mean age 56.1 years) with vertebral osteopenia before and during 2-year treatment with an 800-mg daily dose of clodronate, with a non-amino bisphosphonate. Changes in TRACP 5b were compared with those in urinary excretion of type I collagen amino-terminal telopeptide (U-NTX), corrected for creatinine excretion, a well-established marker of bone resorption, and to serum type I procollagen amino-terminal propeptide (S-PINP), a marker of bone formation. Marker changes 1 year after start of treatment were correlated with changes in bone mineral density (BMD). The least significant change (LSC) for each marker and BMD was calculated from values for subjects receiving placebo. Responders to treatment were those exhibiting a change larger than LSC. In response to clodronate treatment S-TRACP 5b (mean change up to -18%) decreased less than did U-NTX (up to -51%) or S-PINP (up to -46%). Marker changes correlated with changes in lumbar spine and trochanter BMD. The most efficient marker for finding responders to treatment was S-PINP, which changed more than the LSC (32%) in 72% of the subjects at the 1-year time point and in 79% at the 2-year time point. S-TRACP 5b change exceeded the LSC (27%) in 40% and 34% of the subjects at each time point, while U-NTX change exceeded the LSC (55%) in 55% and 40%, respectively. We conclude that, in terms of the proportion of subjects exhibiting any change exceeding the LSC, S-TRACP 5b did not appear to be superior to U-NTX and S-PINP in the follow-up of clodronate treatment. The reason may lie in the mechanism of action of clodronate, which rather than reducing the number of TRACP 5b-secreting osteoclasts, reduces the activity of bone proteolytic enzymes and thus the rate of bone organic matrix degradation. This is seen in decreased amounts of type I collagen breakdown products (U-NTX), and through coupling of bone resorption with bone formation, in a decrease in circulating levels of the marker that reflects new collagen formation (S-PINP).

Acid Phosphatase↗

PubMed2004

Heat shock protein 60 autoimmunity and early lipid lesions in cholesterol-fed C57BL/6JBom mice during Chlamydia pneumoniae infection.

Chronic Chlamydia pneumoniae infection and autoimmunity to heat shock protein 60 (Hsp60) have both been documented to be associated with atherosclerosis. Herein, we studied the effects of C. pneumoniae infection and a diet with a low-cholesterol supplement on the development of autoantibodies to mouse Hsp60 and early lipid lesions in the aortic valve of C57BL/6JBom mice. In addition, pulmonary infection was investigated. C57BL/6JBom mice were given one to three C. pneumoniae inoculations and fed either a regular diet or a diet enriched with 0.2% cholesterol. Autoantibody responses against mouse Hsp60 developed in both diet groups when the mice were infected with C. pneumoniae and in uninfected mice fed a cholesterol-enriched diet. C. pneumoniae infections increased subendothelial foam cell accumulation in mice on a 0.2% cholesterol-enriched diet (p = 0.022), without apparent hypercholesterolemia. These in vivo data suggest that autoantibodies against mouse Hsp60 develop as a consequence of cholesterol feeding and repeated C. pneumoniae infections. Further, infectious burden increased early lipid lesions in C57BL/6JBom mice fed a cholesterol-enriched diet.

Animals↗

PubMed2003

Melanocortin-3-receptor gene variants in morbid obesity.

BACKGROUND: Linkage and knock-out mice studies suggest that the melanocortin-3-receptor (MC3R) is a candidate gene for obesity. OBJECTIVE: To evaluate whether MC3R mutations underlie morbid obesity. SUBJECTS AND METHODS: MC3R coding and 5(')-flanking regions were sequenced in 48 subjects and the detected variants genotyped in 252 morbidly obese (BMI>/=40 kg/m(2)) Finns. Gel shifts were used to examine whether a mutation in the putative promoter alters GATA-factor binding. RESULTS: Three common MC3R variants were found: a 17C>A variant, changing Thr6-->Lys in 16%, a 241G>A variant changing Val81-->Ile in 15%, and a -239A>G substitution in the GATA binding site in 21% of the subjects. Four other variants were detected in the 5(') flanking region. Frequencies of the three common variants did not differ between obese and contol subjects. Among the obese, the 17C>A and 241G>A variants were coinherited and associated with increased insulin-glucose ratios (P<0.05) and leptin levels (P<0.05). GATA-4 bound efficiently to wild type oligonucleotide, but only weakly to the oligonucleotide with the -239A>G mutation. CONCLUSIONS: MC3R gene variants are common and do not explain human morbid obesity. These variants associated with subtle changes in onset of weight gain, hyperleptinemia and insulin-glucose ratios. The -239A>G mutation abolishes binding of GATA-4 to the MC3R promoter region.

Adult↗

PubMed2002

Prevention of bone loss by clodronate in early postmenopausal women with vertebral osteopenia: a dose-finding study.

This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1-5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women ( T-score < or =-1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were -3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD -1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and -0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% ( p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% ( p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% ( p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% ( p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400-800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials.

Absorptiometry, Photon↗

PubMed2002

Recovery of bone mass and normalization of bone turnover in long-term survivors of allogeneic bone marrow transplantation.

Osteoporotic fractures are potential long-term complications of bone marrow transplantation (BMT). We previously reported that bone mineral density (BMD) of patients undergoing allogeneic BMT decreased by 6% to 9% during the first 6 months after BMT and that bone turnover rate was still increased 1 year after BMT. BMT patients do not need lifelong immunosuppressive treatment, which should offer favorable circumstances for the recovery of BMD. Thus, 27 (14 women, 13 men) of 29 long-term survivors of our previous study were invited to a follow-up study at a median of 75 months after BMT. From 12 months after BMT the BMD of the lumbar spine had increased by 2.4% (P = 0.002). The respective changes in femoral sites were +4.1% in the femoral neck (P = 0.087), 4.0% in the trochanter (P = 0.095), +4.7% in Ward's triangle (P = 0.072) and +1.4% in the total hip (P = 0.23). The markers of bone formation, serum osteocalcin and type I procollagen aminoterminal propeptide (PINP) had returned to control levels, but out of the markers of bone resorption the mean level of serum type I carboxyterminal telopeptide (ICTP) was 41% higher (P = 0.0001) and that of urinary type I collagen N-terminal telopeptide/creatinine (NTx) 41% lower (P = 0.0002) in patients than in controls. The mean serum 25-hydroxyvitamin D [25(OH)D] was 33% lower in patients (P = 0.0002), most of whom had hypovitaminosis D [serum 25(OH)D < or = 37 nmol/l]. Except for two, males had serum testosterone level lower than before BMT and four men had hypogonadism. In conclusion, in long-term survivors of allogeneic BMT BMD recovers and bone turnover state normalizes as compared to the situation 1 year after BMT. More attention should be paid to the vitamin D status of all recipients and to possible hypogonadism of male patients.

Adult↗

PubMed2002

Effect of acute Chlamydia pneumoniae infection on lipoprotein metabolism in NIH/S mice.

Chlamydia pneumoniae is a well-known cause of respiratory infections, globally. Chronic C. pneumoniae infection has been associated with atherosclerosis. The aim of the present study was to investigate the effects of acute C. pneumoniae infection on serum lipid levels and some regulatory proteins/enzymes in NIH/S mice. Female mice (n=30) were intranasally infected with 5.3*10(5) inclusion forming units (IFU) of C. pneumoniae and control mice (n = 30) were inoculated with buffer. Six uninoculated mice at day 0 and then six mice from each group 3, 6, 9, 14 and 20 days post-inoculation were killed and serum samples were collected for analysis. Successful infection was confirmed by IgG response to C. pneumoniae and positive Chlamydia cultivation from the lungs. Serum triglycerides and total cholesterol, as well as the activities of hepatic lipase (HL), lecithin-cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) and the concentration of lipopolysaccharide-binding protein (LBP) were analyzed. In C. pneumoniae infected mice, a minor change in triglyceride (corrected p-value 0.020) levels was observed 9 days post-infection (p.i.). LCAT activity declined remarkably, and the lowest activities were measured on day 9 p.i. (67% from the baseline value). HL and PLTP activities did not differ from those in the control group during the whole experimental period. There was a 2.5-fold increase in the serum LBP concentration owing to the C. pneumoniae infection 9 days p.i. The data indicate that acute C. pneumoniae infection, although clinically almost asymptomatic, causes small, transient changes in serum total lipids and some key proteins involved in lipoprotein metabolism in mice.

Acute Disease↗

PubMed2001

Effect of intracerebral 6-nitronoradrenaline, an endogenous catechol-O-methyltransferase (COMT) inhibitor, on striatal dopamine metabolism in anaesthetised rats.

6-Nitronoradrenaline, a bioactive compound recently identified in the brain, is known to inhibit catechol-O-methyltransferase. To study its effect on dopamine metabolism, it was administered into rat striatum via a microdialysis probe. Other nitrated catechols (6-nitrodopamine, 6-nitro-DOPAC and 5-nitro-HVA) were studied for comparison. Tolcapone, a selective catechol-O-methyltransferase inhibitor, was used as a positive reference compound. Both 6-nitronoradrenaline and tolcapone increased striatal extracellular dopamine levels during the perfusion (at 100 microM concentration but not at 10 microM) and decreased the efflux of homovanillic acid. Tolcapone, but not other nitrated catechols, increased 3,4-dihydroxyphenylacetic acid efflux. None of the compounds inhibited MAO-B activity at 100 microM or lower. At 1 mM, 6-nitrodopamine inhibited MAO-B by 60%. Compared to tolcapone, other nitrated catechols were very weak COMT inhibitors in vitro. Neither tolcapone nor 6-nitronoradrenaline modified the metabolism of L-dopa which was given peripherally. In binding studies, both 6-nitronoradrenaline and other nitrocatechols failed to affect the dopamine transporter even at high micromolar concentrations. In conclusion, exogenous 6-nitronoradrenaline can act as a COMT inhibitor in the striatum and elevate striatal dopamine levels without inhibiting dopamine reuptake. Whether endogenous 6-nitronoradrenaline can be formed also in vivo in the striatum and act as a regulator of dopaminergic tone remains to be determined.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Clinical and biochemical response to single infusion of clodronate in active rheumatoid arthritis--a double blind placebo controlled study.

OBJECTIVE: To investigate the efficacy and tolerability of intravenous clodronate in patients with rheumatoid arthritis (RA). TREATMENT AND METHODS: Twenty-six patients with active RA were randomly allocated to receive either a single iv. infusion of placebo or 600 mg clodronate. Efficacy and safety were assessed weekly during the following three weeks by clinical and laboratory evaluations. RESULTS: Serum osteocalcin and carboxyterminal propeptide of type I procollagen (markers of bone metabolism) were significantly decreased in the clodronate group at the end of the study, whereas the indices of disease activity including number of swollen joints, number of tender joints, patient's and doctor's estimation of condition (visual analogue scale), erythrocyte sedimentation rate and serum C-reactive protein level were not affected by clodronate treatment. No serious adverse effects were observed. CONCLUSIONS: A single infusion of clodronate in patients with RA was safe and caused a decline in the markers of bone metabolism, but this short-term treatment did not suppress disease activity. Results from recent clinical and preclinical studies, however, suggest that the anti-inflammatory efficacy of clodronate requires liposome encapsulation.

Adult↗

PubMed2001

Relation of collagen type I alpha 1 (COLIA 1) and vitamin D receptor genotypes to bone mass, turnover, and fractures in early postmenopausal women and to hip fractures in elderly people.

Background: In a previous study, we showed an association between the vitamin D receptor (VDR) gene BsmI restriction fragment polymorphism and peak bone mass in young Finnish adults. Design: The previous finding prompted us to study the relationship of the same polymorphism, as well as of the polymorphism in the Sp1 binding site of the collagen type I alpha 1 (COLIA 1) gene, to bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry and adjusted for age, weight, height, and lifestyle factors. Also studied was the relationship of VDR and COLIA 1 genotypes to markers of bone turnover [serum osteocalcin, type I procollagen carboxy- (PICP), and aminoterminal (PINP) propeptide, and type I collagen carboxyterminal telopeptide (ICTP)] and bone fractures in 513 early postmenopausal women (1-5 years postmenopausal), as well as hip fractures in 172 very old people. Results: The BB, Bb, and bb genotypes of the VDR gene, as well as the SS, Ss, and ss genotypes of the COLIA 1 gene, were distributed similarly among 402 early postmenopausal women with osteopenia in the lumbar spine and among 111 women with normal BMD (P=0.12 for VDR, P=0.53 for COLIA 1). There was no relation between the VDR and COLIA 1 genotypes and lumbar spine BMD among osteopenic women, among normal women, or in the combined study population. Among the women with vertebral osteopenia, the femoral neck BMD did not associate significantly with the VDR or COLIA 1 polymorphisms. The frequencies of the different VDR and COLIA 1 genotypes were similar among women with or without a history of a low-energy fracture. There was a borderline association between the VDR genotype and serum osteocalcin concentrations, with the Bb genotype associated with the highest median level (P=0.037). In a population-based sample of very old individuals (>85 years), the frequencies of the different VDR and COLIA 1 genotypes were similar among those with (n=64) and without (n=108) a history of hip fracture. Conclusion: The present data suggest that, in the Finnish population, the VDR and COLIA 1 genotypes do not determine the bone mass of early postmenopausal women or their bone turnover rate. The polymorphisms are not associated with risk of hip fractures in elderly people or with low-energy fractures in early postmenopausal women.

Journal Article↗

PubMed2001

Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of apolipoprotein E-deficient mice.

In epidemiological studies, an association between cardiovascular disease and Chlamydia pneumoniae (C pneumoniae) infection has been observed. Although C pneumoniae has been shown to be present in atherosclerotic lesions, a causal relationship between C pneumoniae infection and atherosclerosis has not been demonstrated. To study this question, we used 2 strains of apolipoprotein (apo) E-deficient mice. Eight-week-old mice on an FVB background that were maintained on either a low- or a high-fat diet were infected 3 times at 1-week intervals with C pneumoniae, and atherosclerotic lesions were measured in the aortic root at 10 weeks after the primary infection. In each of the diet groups, no difference in the extent of atherosclerosis could be observed between the C pneumoniae-infected and control animals. In further studies, 2 strains of apoE-deficient mice (FVB or C57BL/6J background) were infected 4 times at 3- to 4-week intervals, and the extent of atherosclerosis was analyzed 18 weeks later. The mice were kept on either a low- or a high-fat diet. The high-fat diet increased atherosclerosis, and a difference in atherosclerosis susceptibility between the mouse strains was observed. However, C pneumoniae infection did not influence lesion size in either mouse strain. On the other hand, C pneumoniae could not be demonstrated by polymerase chain reaction in any of the atherosclerotic lesions of the infected animals studied. A small decrease in serum cholesterol and triglyceride levels 3 days after the primary infection occurred, but after that no differences in serum lipid levels compared with those in noninfected animals were evident. In the myocardium of C pneumoniae-infected mice, no inflammatory signs could be observed. We conclude that under the experimental conditions used, C pneumoniae infection does not accelerate atherogenic changes in the aortic root of apoE-deficient mice.

Animals↗

PubMed2001

Comparison of HPLC and small column (CDTect) methods for disialotransferrin.

BACKGROUND: Current methods for determination of carbohydrate-deficient transferrin (CDT) are based on separation of the CDT fraction by ion-exchange chromatography on minicolumns and quantification by immunoassay. Alternatively, the transferrin isoforms can be separated by HPLC anion-exchange chromatography and quantified by absorbance. This method has been reported to improve the validity of CDT as a marker of chronic alcohol abuse. METHODS: HPLC on either MonoQ or ResourceQ anion-exchange columns was used to separate and quantify isoforms of transferrin with detection at 460 nm. The result was expressed as the percentage of the disialo form (pI 5.7) of total transferrin (DST). The commercial CDTect assay was used as a comparison method. Serum samples from nondrinkers (n = 57), moderate drinkers (n = 77), and heavy drinkers (n = 139) were analyzed. RESULTS: In ROC analysis for differentiation between moderate and heavy drinkers, the area under the curve (AUC) for the HPLC method was 0.87 (95% confidence interval, 0.81-0.93), whereas that for CDTect was 0.72 (95% confidence interval, 0.64-0.80). At 90% specificity, the sensitivity of DST was 63% (95% confidence interval, 53-73%) compared with 33% (22-44%) for CDT. The reference interval of the HPLC method was 0.68-1.7%. CONCLUSIONS: The HPLC anion-exchange method for quantification of CDT provides substantially better separation between moderate and heavy drinkers than the CDTect method.

Alcoholism↗

PubMed2000

Bone mass and markers of bone and calcium metabolism in postmenopausal women treated with 1,25-dihydroxyvitamin D (Calcitriol) for four years.

To evaluate the long-term effect of calcitriol treatment on bone mineral density (BMD) of the femoral neck and lumbar spine and the parameters of calcium and bone metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years, were enrolled in the study. Eighteen started a 4-year supplementation with 0.5 microg of calcitriol daily and 37 served as controls. Calcium intake of all the subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by 3.0% in the calcitriol group, but decreased by 1.6% in the control group (P = 0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P = 0.067). Two years' treatment with calcitriol increased the intestinal absorption of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0. 001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01). In the calcitriol group the marker of bone formation, serum osteocalcin, decreased by 27% (P < 0.01), and the marker of bone resorption, serum C-telopeptide of type I collagen (CTx), by 33% (P = 0.05) after 2 years. In two subjects the calcitriol dose had to be reduced because of hypercalciuria. We conclude that calcitriol treatment increases bone mass at the femoral neck and lumbar spine, the increases being maintained for up to 4 years. The gain in bone mass results from reduced bone turnover which is partly a consequence of the enhanced intestinal absorption of calcium and suppressed serum PTH levels.

Absorptiometry, Photon↗

PubMed2000

Timing of food intake has a marked effect on the bioavailability of clodronate.

Because of the low and variable bioavailability of bisphosphonates and the huge effect of food on their gastrointestinal absorption, it is of utmost importance to know the optimal timing of drug intake in relation to food intake. We investigated the effect of time on the bioavailability of clodronate when the drug was administered 2, 1, or 0.5 h before breakfast, with breakfast, or 2 h after breakfast (in the middle of a 4-h fast). The study was conducted as a single-center, open, balanced, randomized, crossover pharmacokinetic study in 31 healthy subjects aged 21 to 34 years. The volunteers participated in five different sessions with 800 mg of oral clodronate, and these sessions were separated by washout phases, each for at least 1 week. The primary pharmacokinetic variables were the area under the serum concentration time curve in 24 h (AUC(0-24)) for clodronate and the maximal concentration of clodronate in serum (C(max)). Clodronate was absorbed rather similarly when taken in the morning on an empty stomach 2, 1, or 0.5 h before breakfast, but because the best absorption occurred (as expected) when the drug was taken 2 h before breakfast, this scheme served as the reference treatment. As evaluated by area under the serum concentration time curves, the dose-breakfast interval of 1 h scarcely reduced absorption from the reference treatment level (relative absorption 91%, p = 1.0). Compared with the reference treatment, clodronate was absorbed with 69% efficacy (p = 0.65) when breakfast followed only 0.5 h later. The dose-breakfast intervals of 0.5 and 1 h did not differ significantly from each other (p = 0.85). Absorption was, however, only 34% (p < 0.0001) of the optimum when the drug was taken 2 h after breakfast, and only 10% of optimal when clodronate was taken with breakfast (p < 0.0001). In conclusion, it can be recommended to take Bonefos capsules in the morning on an empty stomach at least 0.5 h before breakfast.

Adult↗

PubMed2000

The resistance of human monocyte-derived macrophages to Chlamydia pneumoniae infection is enhanced by interferon-gamma.

Chlamydia pneumoniae is an intracellular bacterium which commonly causes respiratory infections. Chronic infections have been associated with atherosclerosis and the organism has been detected in macrophages in the disease lesions. Growth of chlamydiae in different epithelial cell lines is restricted by interferon-gamma (IFN-gamma), a monocyte activator produced by T cells. We have studied the influence of IFN-gamma on the growth and infectivity of C. pneumoniae in HL-cells and human monocyte-derived macrophages. Low concentrations of the cytokine significantly restricted the growth and productivity of C. pneumoniae in epithelial cells in vitro. In macrophages, however, no effect on the growth of the bacteria in infected cells was found, but high doses clearly restricted the production of infectious progeny. The results suggest that IFN-gamma participates in the resistance to C. pneumoniae. The bacterium is, however, still capable of infecting macrophages that are important in the pathogenesis of atherosclerosis and it may thus participate in the inflammatory process associated with the disease.

Cell Line↗