Biomedical subjects

C Lamberg-Allardt

Publications and source records attributed to C Lamberg-Allardt.

At least 19 recordsLinked to original sources

PubMed2006

Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols.

OBJECTIVE: The aim of this study was to investigate whether a plant sterol mixture would reduce serum cholesterol when added to low fat dairy products in subjects with hypercholesterolaemia, and to examine the effects of the mixture on the serum plant sterol and fat-soluble vitamin levels. DESIGN: A parallel, double-blind study. SETTING: The study was performed in three different locations in Finland. SUBJECTS: In total, 164 mildly or moderately hypercholesterolaemic subjects participated in the study. METHODS: The subjects were randomly divided into two groups: a plant sterol group and a control group. The subjects consumed the products for 6 weeks after a 3-week run-in period. The targeted plant sterol intake was 2 g/day in the sterol group. RESULTS: During the treatment period, there was a 6.5% reduction in serum total cholesterol in the sterol group while no change was observed in the control group (P<0.0005). Serum low-density lipoprotein (LDL) cholesterol was reduced by 10.4% in the sterol group and by 0.6% in the control group (P<0.00005). There was no change during the trial in serum high-density lipoprotein (HDL) cholesterol or triacylglycerol concentrations. The HDL/LDL cholesterol ratio increased by 16.1% in the sterol group and by 4.3% in the control group (P=0.0001). Serum plant sterol levels increased significantly (P=0.0001) in the sterol group. None of the fat-soluble vitamin levels decreased significantly when changes in serum total cholesterol were taken into account. The hypocholesterolaemic effect of sterol administration was not influenced by apolipoprotein E phenotype. CONCLUSIONS: Yoghurt, low-fat hard cheese and low-fat fresh cheese enriched with a plant sterol mixture reduced serum cholesterol in hypercholesterolaemic subjects and no adverse effects were noted in the dietary control of hypercholesterolaemia.

Anticholesteremic Agents↗

PubMed2005

A 7-week reduction in salt intake does not contribute to markers of bone metabolism in young healthy subjects.

BACKGROUND: Sodium intake increases urinary calcium excretion and may thus lead to negative calcium balance and bone loss. OBJECTIVE: We hypothesised that reducing sodium intake would reduce urinary calcium excretion and have a beneficial influence in bone metabolism. DESIGN: A total of 29 subjects, 14 males and 15 females, were divided into two study groups. One group (low-sodium group (LS)) reduced sodium intake for 7 weeks by substituting low-salt alternatives for the most important dietary sources of sodium. The other group, serving as a control group (C), was given the same food items in the form of normally salted alternatives. Fasting serum samples as well as 24-h urine samples were obtained in the beginning and at the end of the study. Urinary sodium, urinary calcium, urinary creatinine, serum calcium, serum phosphate, serum creatinine, serum parathyroid hormone (s-PTH), serum C-terminal telopeptides of Type-I collagen and serum bone alkaline phosphatase (s-B-ALP) were analysed. RESULTS: The LS group showed a significant decline (P = 0.001) in urinary sodium/creatinine ratio without a significant effect on urinary calcium/creatinine ratio. In the LS group, s-PTH increased (P = 0.03). The C group showed an increase in s-PTH (P = 0.05) and in s-B-ALP, but no differences were observed between the study groups in the changes of serum markers of calcium and bone metabolism. CONCLUSIONS: We have shown that reducing the sodium intake of young, healthy people with adequate calcium intake over a 7-week period does not affect the markers of bone metabolism.

Adult↗

PubMed2005

Teenage girls and elderly women living in northern Europe have low winter vitamin D status.

OBJECTIVE: To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD) in adolescent girls and elderly community-dwelling women living in four countries of northern Europe and to explain differences in S-25OHD concentrations between and within the countries. DESIGN: A cross-sectional observational study conducted in a standardised way during February-March. S-25OHD was analysed by high-performance liquid chromatography. Vitamin D and calcium intake was calculated using a standardised food composition database. SETTING: Denmark, Finland, Ireland, and Poland. SUBJECTS: A total of 199 girls (mean (s.d.) age 12.6 (0.5) y) and 221 women (mean (s.d.) age 71.8 (1.4) y). RESULTS: The median (inter quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in 37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in 92% of the girls and 37% of the women. Positive significant determinants for S-25OHD in girls were use of vitamin D supplements, and in women sun habits, dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass index and smoking were negative determinants in women. For women predictors could explain the differences between countries (P(country) = 0.09, R(2) = 0.39), but for girls the difference remained significant even after including predictors (P(country) = 0.03, R(2) = 0.15). CONCLUSION: Vitamin D status is low in northern Europe during winter. More than one-third of the adolescent girls have vitamin D status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of vitamin D supplements is a significant positive determinant for S-25OHD for both girls and women (P = 0.001). SPONSORSHIP: The European Fifth Framework Programme (Contract No. QLK1-CT-2000-00623).

Age Factors↗

PubMed2005

Food consumption and nutrient intakes with a special focus on milk product consumption in early pubertal girls in Central Finland.

OBJECTIVE: To evaluate the current status of dietary intakes in early pubertal girls with a special focus on milk products. DESIGN: Cross-sectional data using 3-day food records. SUBJECTS: Eight hundred and sixty girls, aged 10-12 years, at Tanner maturation stage I-III. RESULTS: The mean consumption of milk products (620 g day(-1)) was similar to that of a Finnish study in the 1980s, while the consumption of non-milk drinks (403 g day(-1)) had increased. Twelve per cent of the girls had a dairy-restricted diet and consumed significantly less milk products than girls with a non-restricted diet (465 vs. 644 g day(-1), P<0.001). Girls with low milk product consumption had the highest non-milk drinks consumption (P<0.001). The mean energy intake was 7.1 MJ day(-1). No major changes were found in the sources of nutrients. The shares of energy for nutrients were close to recommendations except for saturated fat (13.9 vs. 10% of energy) and carbohydrates (51.5 vs. 55-60% of energy). The mean calcium intake (1117 mg day(-1)) was above the recommendation, while the vitamin D intake (3.1 microg day(-1)) of 88% of the girls was below the recommendation. CONCLUSIONS: The diet quality of early pubertal girls is close to the recommendations and has improved with respect to fat compared with the 1980s. Consumption of milk products is high although the consumption of non-milk drinks has increased. We found a subgroup of girls who compensate their low milk product consumption with a higher consumption of non-milk drinks. Following a dairy-restricted diet is the main reason for low consumption of milk products.

Analysis of Variance↗

PubMed2003

Dietary calcium intake in premenopausal Bangladeshi women: do socio-economic or physiological factors play a role?

OBJECTIVE: Evaluation of data on dietary calcium intake in premenopausal women of two socio-economic groups in Bangladesh. DESIGN: A cross sectional study. Three days dietary records were used to estimate habitual calcium intake. SETTING: Two regions of Bangladesh. The Dhaka city area and the Betagair Union in the sub-district Nandail, Mymensingh. SUBJECTS: A total of 191 subjects of two groups (low socio-economic group=group L, n=101 and high socio-economic group=group H, n=90) of Bangladeshi women aged 16-40 y. About 87% of the subjects were housewives and the rest 13% were distributed in other different professions. Each group consisted of three sub-groups (non-pregnant non-lactating=1, pregnant=2 and lactating=3). RESULTS: : The influence of socio-economic status on dietary intake of calcium (P<0.001) was observed in this study. The dietary intake of calcium was influenced by physiological status (PS) in high income group only (P<0.005). The mean dietary calcium intake was significantly higher (P&<0.005) in all sub-groups of this group compared with the corresponding sub-groups in low income group. Although in group H, 47% of subjects failed to meet even the lowest level (400-500 mg/day) of WHO recommended dietary allowances (RDA) of calcium for adult women. No subject in group L was found to meet the RDA level. Moreover, 63% of the women in group L had calcium intake lower than 200 mg/day. These figure could be more critical in both groups if we consider the recent USA-RDAs of calcium for adult women (1000 mg/day). The observed sources of dietary calcium were different in the two groups. CONCLUSIONS: The results of the study suggested that low calcium intake could reduce the bone accretion rates and increase the risk of osteoporosis in the subjects of the present study. Calcium rich food may be recommended for women in both groups.

Adolescent↗

PubMed2002

Vitamin D deficiency: a concern in premenopausal Bangladeshi women of two socio-economic groups in rural and urban region.

OBJECTIVE: The study was designed to evaluate the vitamin D status in women of different physiological status of two socio-economic groups in Bangladesh. DESIGN: A cross-sectional study, using serum 25-hydroxyvitamin D (25-OHD), calcium, phosphorus and alkaline phosphatase activity. SETTING: Two regions of Bangladesh. The Dhaka city area and west region of Nandail (Betagair Union), Mymensingh. SUBJECTS: Representative subjects of two groups (low socio-economic group=group L, n=99; and high socio-economic group=group H, n=90) of Bangladeshi women aged 16-40 y. About 87% of the subjects were housewives and the rest, 13%, were distributed among other different professions. Each group comprised of three sub-groups (non-pregnant non-lactating=1, pregnant=2, and lactating=3). RESULTS: The influence of socio-economic status and physiological status on serum 25-OHD concentration (P=0.038, P=0.015, respectively), serum calcium concentration (P<0.001, P<0.001, respectively) and alkaline phosphatase activity (P<0.001, P<0.001, respectively) were observed. The distribution of serum 25-OHD concentration in both groups was shifted overall toward the lower limit of the normal range. Seventeen percent of women in group L and 12% of women in group H had serum 25-OHD concentration <25 nmol/l. Hypovitaminosis D (serum 25-OHD concentration < or = 37.5 nmol/l) was observed in 50% of subjects in group L and 38% of subjects in group H, respectively. The prevalence of hypovitaminosis was higher in lactating subjects of the groups L and H (63 and 46%, respectively) than in the other sub-groups in the same group. CONCLUSIONS: The results of the study suggested that women in Bangladesh were at risk of hypovitaminosis D and lactation was an additional risk factor in low income groups. The situation may increase the risk of bone loss.

Adult↗

PubMed2001

Bone mineral metabolism after total gastrectomy.

Gastric surgery is mostly needed for treatment of gastric malignancy. To investigate the effect of total gastrectomy on bone mineral density (BMD) and bone mineral metabolism we evaluated 18 patients after total gastrectomy. Mean interval since operation was 71 +/- 20 months. BMD results were compared with age- and gender-matched controls (n = 46) and also expressed as T and Z scores. Bone mineral density measured by dual-energy X-ray absorptiometry (DXA) was found to be significantly lower in patients after total gastrectomy compared with healthy controls in the lumbar spine (p = 0.017 for women, p = 0.002 for men), femoral neck (p = 0.004 for women, p = 0.001 for men), Ward's triangle (p = 0.031 for women, p = 0.003 for men), and greater trochanter (p = 0.001 for women, p = 0.001 for men). Z scores for lumbar spine, femoral neck, Ward's triangle, and greater trochanter were -0.83, -1.54, -1.02, and -1.19, respectively. Biochemical measurements correlated poorly with BMD and were found to be of lesser value in diagnosing reduced bone mass as well as in differential diagnosis of etiology of osteopenia. The results of our study show the deleterious effect of total gastrectomy on bone mineral status and suggest an increased fracture risk in these patients.

Absorptiometry, Photon↗

PubMed2001

Iron status of premenopausal women in two regions of Bangladesh: prevalence of deficiency in high and low socio-economic groups.

OBJECTIVE: The objective of the study was to assess iron status in women of different physiological status of two socio-economic groups in Bangladesh. DESIGN: Cross sectional study, using 3-day food record and blood haemoglobin, serum iron, serum ferritin concentrations. SETTING: Two regions of Bangladesh. The Dhaka city area and west region of Nandail, Mymensingh. SUBJECTS: Women aged 16-40 y. The low socio-economic group (group L, n=101) consisted of rural women with precarious income levels. The high socio-economic group (group H, n=90) consisted of women with high income and educational levels. The groups were composed of three sub-groups (non-pregnant non-lactating=1, pregnant = 2 and lactating = 3). RESULTS: There was no significant difference between the corresponding sub-groups of the two socio-economic groups in dietary intake of iron. In all sub-groups, the intake of iron was much higher than the RDA level and mainly based on non-haem iron. Blood haemoglobin (B-Hb) concentration (P=0.000), serum iron concentration (P=0.005) and serum ferritin (SF) concentration (P=0.000) were affected by socio-economic status. Physiological status (PS) influenced the B-Hb concentration (P=0.000). Prevalence of anaemia ranged from 63 to 70% in group L and 27 to 66% in group H, respectively. The prevalence of empty iron store (SF concentration<12 microg/l) ranged from 35 to 59% in group L and 15 to 32% in group H, respectively. The prevalence of anaemia and iron deficiency (70 and 35% for sub-group L2; 66 and 32% for sub-group H2, respectively) were similar in the pregnant subjects of the two groups. CONCLUSIONS: Subclinical iron deficiency was common in women of low socio-economic status. The pregnant subjects in the two groups was similar as regards iron status. SPONSORSHIP: The study was supported by the Academy of Finland, University of Helsinki and NorFa, Norway.

Adolescent↗

PubMed2000

Inactivation of atrial natriuretic factor-stimulated cyclic guanosine 3',5'-monophosphate (cGMP) in UMR-106 osteoblast-like cells.

Previous studies have suggested a role of cyclic guanosine 3', 5'-monophosphate (cGMP) in the differentiation and proliferation of osteoblasts. We studied the effect of ANF (atrial natriuretic factor) on intracellular cGMP accumulation, cGMP efflux, and cGMP-phosphodiesterase (PDE) activity in UMR-106 osteoblast-like cells. ANF rapidly increased both intracellular cGMP and cGMP efflux. ANF-stimulated intracellular cGMP peaked at 2 min in the absence and at 10 min in the presence of 0.25 mM 3-isobutyl-1-methylxanthine. Probenecid, an antagonist of anion transport, blocked the efflux of cGMP (IC(50) = 0.1 mM), ruling out simple diffusion as a mechanism of the efflux. cGMP-PDE activity was increased threefold in crude homogenates from ANF-treated cells (IC(50) = 23 nM). ANF-evoked stimulation of cGMP-PDE activity was reached simultaneously with the peak in intracellular cGMP. Separation of the PDEs by Q-Sepharose chromatography revealed three cGMP-hydrolyzing peaks. The first peak was sensitive to the PDE5 (cGMP-specific PDE) isoenzyme-selective inhibitor zaprinast (IC(50) = 0.45 microM). The second peak was stimulated fourfold by the addition of calcium/calmodulin, indicating the presence of PDE1. The third peak was sensitive to the PDE2 (cGMP-stimulated PDE) isoenzyme-selective inhibitor 9-[2-hydroxy-3-nonyl]adenine (EHNA) (IC(50) = 3 microM), and was activated by over 300% in the presence of 4 microM cGMP. Our results show that ANF-stimulated cGMP is released from UMR-106 cells by a probenecid-sensitive mechanism. ANF also stimulates cGMP hydrolysis by activating cGMP-PDE activity. Three distinct cGMP-hydrolyzing PDEs, namely PDE5, PDE1, and PDE2, are present in the studied cells.

Animals↗

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↗

PubMed1999

Regulation of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in UMR-106 osteoblast-like cells: role of cAMP-phosphodiesterase and cAMP efflux.

The present study aimed to define the role of adenosine 3',5'-cyclic monophosphate (cAMP)-phosphodiesterase (PDE) activity and the possible involvement of cAMP efflux on parathyroid hormone (PTH)-stimulated intracellular cAMP accumulation in cultured osteoblast-like UMR-106 cells. Treatment of the cells with 10 nM PTH (1-84) rapidly increased the level of intracellular cAMP. PTH stimulation also increased the cAMP efflux rate. The efflux of cAMP could only account for a minor part of the decrease in intracellular cAMP. Six peaks of cAMP-hydrolyzing PDE activity were separated by Q-Sepharose chromatography. The first peak to elute was stimulated by Ca2+/calmodulin and provided less than 2% of the total eluted cAMP-PDE activity. The second peak, providing less than 4% of the cAMP-PDE activity, was stimulated 3-fold by 4 microM cyclic GMP (cGMP) and was sensitive to the PDE2 isoenzyme-selective inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). The third peak, providing less than 10% of the cAMP-PDE activity, was insensitive to rolipram, EHNA, Ca2+/calmodulin, and cGMP. Peaks 4, 5 and 6 were sensitive to rolipram (IC50 < 0.1 microM) and provided approximately 85% of the total cAMP-hydrolyzing activity. It is concluded that cAMP-PDE activity in UMR-106 cells plays a major role in the control of intracellular cAMP accumulation, whereas only moderate amounts of cAMP are extruded from the cells through cAMP efflux. The main cAMP-hydrolyzing PDE isozyme is cAMP-specific/rolipram-sensitive. Ca2+/calmodulin-stimulated PDE, cGMP-stimulated PDE, and presently unidentified cAMP-specific/rolipram-insensitive PDE are also present in UMR-106 cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1999

Bone recovery after a gluten-free diet: a 5-year follow-up study.

The purpose of our study was to investigate the recovery of bone disease in celiac patients during 5 years of a gluten-free diet. The study group consisted of 28 newly diagnosed celiac patients (9 men, 19 women) recruited between 1990 and 1991. Six patients withdrew from the 5-year follow-up. Compliance with the gluten-free diet was good: 96% at 1 year and 82% at 5 years. During the follow-up period, the body mass index increased significantly (8%). Both in men and women, bone mineral density (BMD) values determined by dual X-ray absorptiometry (DXA) increased at the lumbar spine (2%), the femoral neck (1%), the trochanter (6%), and the Wards' area (3%) during the follow-up. The increase in BMD was found already during the first year of follow-up. After 1 year, BMD increased or remained the same in 69% of the patients at the lumbar spine and in 67% of the patients at the femoral neck, 89% of patients at the throchanter, and 67% of patients at the Wards' area. During the 5-year follow-up, these figures were 52%, 46%, 68%, and 59%, respectively. At the baseline, 19 out of 28 patients, after 1 year, 14 out of 26 patients, and after 5 years, 2 out of 26 patients had low serum 25(OH)D vitamin values (p = 0.0001). A high serum parathormone value was noticed in 6 out of 25 patients at the baseline, but after 1 year, 5 of them showed normalized values (p = 0.03). According to our results, bone disease in celiac patients is cured in most patients during 5 years on a gluten-free diet. The improvement in BMD mostly occurred already within the first year after the establishment of a gluten-free diet.

Absorptiometry, Photon↗

PubMed1999

Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls.

OBJECTIVES: To study the prevalence of hypovitaminosis D, the effect of vitamin D supplementation on serum 25-hydroxyvitamin D [S-25(OH)D], and the intakes of vitamin D and calcium in Finnish 9- to 15-year-old athletic and nonathletic girls. DESIGN: 1-year follow-up study (February 1997-March 1998) with three months of vitamin D supplementation (10 microg/d) from October to January. SETTING: Turku University Central Hospital, Finland. SUBJECTS: 191 female volunteers aged 9-15 y (131 athletes and 60 controls). METHODS: Vitamin D and calcium intakes were estimated by a four-day food recording and a semi-quantitative food frequency questionnaire (FFQ). S-25(OH)D was followed by radioimmunoassay (RIA). RESULTS: At baseline the mean S-25(OH)D concentration was 33.9 nmol/l among all girls. In winter severe hypovitaminosis D (S-25(OH)D < 20 nmol/l) occurred in 13.4% of the participants and in 67.7% S-25(OH)D was below 37.5 nmol/l. By the next summer the mean S-25(OH)D concentration was 62.9 nmol/l and in 1.6% of the subjects it was below 37.5 nmol/l. The prevalence of severe hypovitaminosis D was not significantly reduced by three months of vitamin D (10 microg/d) supplementation. At baseline, the mean intake of vitamin D was 2.9 microg/d by food recording and 4.3 microg/d by FFQ. The mean calcium intake was 1256 mg/d and 1580 mg/d, respectively. The intakes of vitamin D and calcium remained unchanged during the follow-up period. The athletes consumed more calcium than nonathletic controls, whereas the intake of vitamin D was quite similar among both groups. The vitamin D intake by FFQ correlated with the S-25(OH)D concentration in wintertime (r = 0.28, P < 0.01). CONCLUSION: Hypovitaminosis D is fairly common in growing Finnish girls in the wintertime, and three months of vitamin D supplementation with 10 microg/d was insufficient in preventing hypovitaminosis D. The daily dietary vitamin D intake was insufficient (< 5 microg/d) in the majority of participants, while the calcium intake was usually sufficient.

25-Hydroxyvitamin D 2↗

PubMed1999

Addition of inulin to breakfast does not acutely affect serum ionized calcium and parathyroid hormone concentrations.

BACKGROUND/AIMS: The aim of the present study was to investigate the effects of inulin on calcium metabolism. The study consisted of two separate parts both of which had a randomized two-period cross-over design. METHODS: Fifteen young healthy women volunteered to participate in this study. During the first part of the study, cheese containing 210 mg of calcium, either with 15 g of inulin or without any inulin, was ingested at breakfast, and in the second part, 210 mg of calcium as a supplement, either with 15 g inulin or without inulin, was ingested. The whole day's diet was standardized. Before breakfast, and 2, 4, 6 and 8 h after breakfast, a blood sample was taken, and intact parathyroid hormone (iPTH), ionized calcium (iCa) and total calcium were measured. Urine was collected throughout the day, and the 8-, 12- and 24-hour calcium excretion was calculated. RESULTS: The iPTH or iCa concentration curves (AUCs) did not differ over 8 h, whether or not inulin was consumed at breakfast. The postload urinary calcium excretion was not affected by the inulin. CONCLUSION: Fifteen grams of inulin in fresh cheese or with a calcium supplement (210 mg Ca) taken at breakfast does not acutely affect the markers of calcium metabolism as opposed to a corresponding breakfast without inulin.

Adult↗

PubMed1997

Transdermal oestradiol gel in the treatment of the climacterium: a comparison with oral therapy.

OBJECTIVE: To compare two doses of a transdermal oestradiol gel (Divigel/Sandrena) plus oral sequential medroxyprogesterone acetate (MPA) with oral oestradiol valerate plus oral sequential MPA (Divina/Dilena). DESIGN: Two year, randomised, open-label, comparative study. SETTING: Menopausal outpatient clinic in Helsinki. SUBJECTS: Postmenopausal women with climacteric complaints or already using HRT. INTERVENTIONS: (1) One gram gel containing 1 mg oestradiol for 3 months plus 20 mg oral MPA during the last 14 days; (2) 2 g gel containing 2 mg oestradiol for 21 days plus 10 mg oral MPA during the last 14 days; (3) 2 mg oestradiol valerate tablets for 3 weeks plus 10 mg oral MPA during the last 10 days. In all groups, each treatment period was followed by a 7-day medication-free interval. MAIN OUTCOME MEASURES: Climacteric complaints, bleeding control, bone mineral density, biomarkers of bone metabolism, lipid profile, tolerability and safety. RESULTS: With each preparation, climacteric complaints were significantly reduced and good bleeding control was obtained. In addition, maintenance of bone mineral density as well as a reduction of bone turnover was achieved in all groups. Lipid parameters showed no unfavourable changes. Continuation rates were similar in all groups with overall 74% of patients completing the first year, whereas 94% of patients who elected to continue completed the second year. Tolerability of the gel was good: only 1.7% of patients discontinued treatment due to skin irritation. CONCLUSIONS: Transdermal oestradiol gel and oral oestradiol valerate tablets, used in combination with oral sequential MPA, are effective regimens of HRT in postmenopausal women. Transdermal oestradiol gel is an efficient, well-tolerated form of HRT.

Administration, Cutaneous↗

PubMed1997

Rapid protein kinase A--mediated activation of cyclic AMP-phosphodiesterase by parathyroid hormone in UMR-106 osteoblast-like cells.

Parathyroid hormone (PTH) plays an essential role in osteoblast proliferation and differentiation. The effects of PTH are known to be mediated by cyclic adenosine monophosphate (cAMP) and calcium and by the activation of protein kinase C (PKC). cAMP is hydrolyzed to the inactive form 5' AMP by cyclic nucleotide phosphodiesterases (PDEs). We have investigated the role of PTH on PDE regulation in UMR-106 osteoblast-like cells. Treatment with 10 nM PTH caused a 3-fold increase in the PDE activity. The activation of PDE could be seen within 2 minutes and reached maximal levels after 20 minutes. The PTH effect was dose dependent with a half-maximal dose of 2 nM. The effect of PTH could be mimicked by the cAMP analogs Bt2 cAMP and forskolin, but not by PTH fragment 3-34, calcium ionophore A23187, or by the PKC activator phorbol 12-myristate 13-acetate. The PDE activity stimulated by PTH could be abolished by the PKA inhibitor H-8. The PDE activated by PTH was inhibitable by low concentrations of the cAMP-PDE-specific inhibitor RO 20-1724 (IC50 = 0.2 microM), but not by low concentrations of the inhibitors of cGMP-stimulated and cGMP-inhibited PDEs MEP-1 and milrinone (IC50 for both compounds > 30 microM). The PTH-stimulated cAMP accumulation was potentiated about 7-fold in the presence of RO 20-1724. H-8 potentiated the PTH-stimulated cAMP accumulation about 4-fold. Our results show that PTH rapidly stimulates the activity of cAMP-PDE in UMR-106 cells. The PDE activation involves cAMP and PKA. Inhibition of PKA can abolish the PTH-stimulated PDE activation and leads to increased accumulation of intracellular cAMP.

Animals↗

PubMed1996

Effects of bright light on sleepiness, melatonin, and 25-hydroxyvitamin D(3) in winter seasonal affective disorder.

Sixteen patients with winter seasonal affective disorder and 13 healthy controls were exposed to 3300 lx of cool-white fluorescent light for either 1 hour or 15 min in the morning for 2 weeks during the winter. Subjective sleepiness, melatonin concentration in saliva, and serum 25-hydroxyvitamin D(3) concentration were measured before and after the 2-week trial as well as the following summer when the patients were well. There were no significant differences in the baseline values between the patients and healthy subjects. No significant differences in the outcome measures were observed in the patients or the controls in the two groups of each after the trial. The exposure to bright light resulted in a significant decrease in subjective sleepiness early in the evening in the patients but not in the control subjects. The reduction of depressive symptoms was associated with the decrease in subjective sleepiness but not with the changes in the melatonin or vitamin D concentrations.

Adult↗

PubMed1996

An acute intake of phosphate increases parathyroid hormone secretion and inhibits bone formation in young women.

We studied the effects of a single oral phosphate (Pi) dose as well as those of three consecutive oral phosphate doses on calcium and bone metabolism. In the first part of the study (P1 study) 10 female volunteers were given orally 1500 mg of Pi in water, as a single dose, or plain water in randomized order at two different sessions. In the second part of the study (P3 study), 10 female volunteers were given orally 1500 mg of Pi, as three separate 500 mg doses in water, or plain water in randomized order. Calcium and bone metabolism was monitored for 24 h by measuring the concentrations of serum ionized calcium (S-iCa), urinary calcium, serum phosphate (S-P), urinary P, serum intact parathyroid hormone (PTH), serum carboxy-terminal propeptide of type I collagen (PICP), serum osteocalcin (BGP), serum carboxy-terminal telopeptide of type I collagen (ICTP), urine deoxypyridinoline (DPD) and bone-specific alkaline phosphatase activity (B-ALP). The S-P increased (p = 0.00005 and p = 0.0005, in the P1 and P3 studies, respectively), the S-iCa concentration declined significantly only in the P1 study (p = 0.0014), the urinary calcium excretion decreased (p = 0.02 and 0.013, in the P1 and P3 studies, respectively), and the PTH concentration rose (p = 0.0083 and p = 0.014, in the P1 and P3 studies, respectively) during the phosphate experiment as compared with the control session. Of the three markers of bone formation studied, PICP declined in the P1 study (p = 0.04), and B-ALP declined in both parts of the study (p = 0.027, p = 0.026, in the P1 and P3 studies, respectively) after phosphate administration, whereas there was no significant change in BGP in either of the studies. The markers of bone resorption, ICTP and DPD, were unaffected by the phosphate load in both studies. In conclusion, acute ingestion of phosphate leads to an increase in S-P, a decrease in S-iCa, and an increase in intact PTH secretion. Our results indicate that these events may lead to an acute inactivation of the early phases of bone formation. In this setting, there was no indication of enhanced bone resorption despite the increase in PTH secretion, which could be due to the combined effect of phosphate and PTH on bone resorption.

Administration, Oral↗