Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This randomized, controlled study evaluated the bioavailability of phylloquinone from an intravenous lipid emulsion. A mild vitamin K deficiency was induced in 12 healthy adult men and women by dietary restriction of phylloquinone (40 microg/d, days 1-11) and by administration of warfarin (1.0 mg/d, days 5-11). On day 11, subjects received a 500-mL intravenous solution of either lipid or saline, both of which contained 154 microg phylloquinone. Bioavailability was assessed by serial measurements of plasma phylloquinone, vitamin K1-2,3-epoxide. PIVKA-II (proteins induced by vitamin K absence or antagonists-II), and percentage undercarboxylated osteocalcin. As a result of vitamin K deficiency and minidose warfarin, vitamin K1-2,3-epoxide, PIVKA-II, and percentage undercarboxylated osteocalcin increased significantly between days 1 and 11 (P = 0.05, 0.016, and 0.001, respectively). With the infusions, plasma phylloquinone increased in both groups (P = 0.001). After the infusions vitamin K,-2,3-epoxide decreased in both groups (P = 0.002). Changes in plasma phylloquinone and vitamin K1-2,3-epoxide were no different in the two groups (mean areas under the curves +/- SEM: 116+/-13 nmol x h/L for the saline group and 102+/-20 nmol x h/L for the lipid group for phylloquinone; 38.6+/-7.5 nmol x h/L for the saline group and 31.3+/-9.0 nmol x h/L for the lipid group for vitamin K1-2,3-epoxide). PIVKA-II decreased significantly from baseline values (P = 0.005) in both groups after the infusions. Intravenous lipid reversed the effects of minidose warfarin and of dietary restriction of phylloquinone on hemostasis and vitamin K nutritional status. This reversal was no different from that seen with the infusion of phylloquinone in a saline solution.
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PMID:Bioavailability of phylloquinone from an intravenous lipid emulsion. 953 19

A diurnal variation exists in blood levels of the vitamin K-dependent bone protein osteocalcin. However, it is not known whether the carboxylated and undercarboxylated constituents of osteocalcin also vary. Therefore, osteocalcin and undercarboxylated osteocalcin were measured in specimens collected every 4 hours over a 24-hour period in nine healthy subjects (five males, four females) ages 20-33 years who were consuming a mixed diet containing 100 microg of phylloquinone. Osteocalcin and undercarboxylated osteocalcin were measured by radioimmunoassay (RIA) before and after treatment with barium sulfate. Although the percent undercarboxylated osteocalcin did not change, a diurnal variation was observed in total osteocalcin, carboxylated osteocalcin, and undercarboxylated osteocalcin, with peak concentrations at 4 a.m. and the lowest concentrations between 12 p.m. and 4 p.m. The difference between the total osteocalcin peak and trough concentrations averaged 28 +/- 7 (SEM)%. There were no gender differences in these rhythms. The effect of dietary phylloquinone as a modulator of these rhythms was evaluated in a randomized study by increasing phylloquinone intake to 420 microg/day with fortified corn oil, split between the lunch and dinner meals. Total and carboxylated osteocalcin fluctuations and concentrations were not affected by the dietary treatment. The diurnal variation in undercarboxylated osteocalcin was abolished with supplementation and concentrations at 8 a.m. (14 hours following supplementation) (2.3 +/- 0.2 ng/ml) were significantly lower than the unsupplemented levels (2.7 +/- 0.2 ng/mL, P = 0.006). The percentage of undercarboxylated osteocalcin was similarly decreased after supplementation (19.7 +/- 1.3%) in relation to the mixed diet cycle (24.2 +/- 1.6%, P = 0.006) at 8 a.m. on the second day. Dietary supplementation induced a fluctuation in percentage undercarboxylated osteocalcin with a decline in levels starting at approximately 12 a.m. Therefore, additional dietary phylloquinone does not appear to modulate the total osteocalcin diurnal rhythm, but can influence its undercarboxylated component.
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PMID:Diurnal variation in total and undercarboxylated osteocalcin: influence of increased dietary phylloquinone. 954 23

Hexarelin, a powerful GH-releasing peptide, is capable of causing profound GH release in normal subjects after oral, intranasal, i.v., and s.c. administration. The effect of long-term administration on GH levels in adults is unknown. We have, therefore, assessed the effects of 16 weeks of twice-daily s.c. hexarelin therapy (1.5 micrograms/kg BW) on the GH response to a single injection of hexarelin, and also the GH response to hexarelin 4 weeks after cessation of hexarelin therapy. We have also assessed the effects of chronic hexarelin therapy on serum insulin-like growth factor (IGF)-I, IGF binding protein-3, markers of bone formation (osteocalcin, procollagen-type-III-N-terminal-peptide, and C-terminal propeptide of type I collagen), and resorption (urinary deoxypyridinoline and pyridinoline), body composition, and bone mineral density. The mean (+/- SEM) area under the GH curve (AUCGH) at weeks 0, 1, 4, 16, and 20 were 19.1 +/- 2.4 micrograms/L.h, 13.1 +/- 2.3 micrograms/L.h, 12.3 +/- 2.4 micrograms/L.h, 10.5 +/- 1.8 micrograms/L.h, and 19.4 +/- 3.7 micrograms/L.h, respectively. There was a significant change in AUCGH over the study period (P = 0.0003). Further analysis showed that, compared with baseline, the decrease in AUCGH at week 4 and week 16 were significant (P < 0.05 and P < 0.01, respectively). Four weeks after completion of hexarelin therapy, the AUCGH increased significantly, compared with AUCGH at week 16 (P < 0.05), and was not significantly different from that at week 0. Serum IGF-I and IGF binding protein-3 did not change significantly over the 20-week period (P = 0.24 and P = 0.74, respectively). Of the bone markers measured, only serum C-terminal propeptide of type I collagen changed significantly and was higher at week 16, compared with baseline (P = 0.019). Total body fat, lean body mass, and bone mineral density had not changed significantly at week 16, compared with baseline (P = 0.6, P = 0.3, and P = 0.3, respectively). In summary, we have demonstrated that chronic hexarelin therapy results in a partial and reversible attenuation of the GH response to hexarelin. In the present study, the biological impact of this hexarelin schedule on the GH-IGF-I axis seems to be minimal. The therapeutic potential of chronic hexarelin requires further investigation.
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PMID:Growth hormone status during long-term hexarelin therapy. 958 71

The aim of the present study was to assess diurnal levels of serum osteocalcin in normal children using a recently introduced fluoroimmunoassay (Pharmacia Osteocalcin CAP FEIA) measuring solely the intact peptide. Five girls and two boys aged 10.4-13.6 (mean 12.2) y were studied. Blood samples for determination of osteocalcin were collected every 2h throughout the day. A statistically significant rise in serum osteocalcin (F = 6.7, p < 0.001) with a peak at 08.00 h and a nadir lasting from 10.00 to 24.00 h was found. Trough and peak levels (at 16.00 and 08.00 h, respectively) were 41.6 +/- 6.8 and 66.0 +/- 10.5 microg l(-1) (mean +/- SEM). The circadian variation should be taken into consideration when single assessments of serum osteocalcin in children are performed.
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PMID:Diurnal rhythm of serum osteocalcin in normal children. 976 85

Osteoblastic cells cultured on microcarriers in bioreactors are a potentially useful tool to reproduce the in vivo three-dimensional (3D) bone network. The aim is to compare different types of 3D and two-dimensional (2D) osteoblastic culture. ROS17/2.8 cells are cultured in a bioreactor (rotating-wall vessel) or in two kinds of control (3D petri dish, 3D Percoll) and on two types of microcarrier (Cytodex 3 and Biosilon). Growth and morphology are determined by cell count and SEM, and differentiation is determined by dosage of alkaline phosphatase (ALP) activity and northern blots (ALP and osteocalcin (OC)). SEM shows that Biosilon microcarriers are the best substrate. Proliferation in the RWV and 3D petri dish is still in the exponential phase, whereas growth in the 2D culture reaches a plateau after eight days of culture. ALP activity and the ALP and OC mRNA levels are similar at day 8 for both the RWV and 3D petri dish. However, at day 10, cells are more differentiated in the RWV. The study shows that osteoblasts are both proliferate and differentiate in 3D structures. A BrDU immunocytochemical approach shows that only the cells in the periphery of the aggregates proliferate. Therefore the bioreactor may be a suitable tissue culture model for investigation of growth and differentiation processes in tissue engineering.
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PMID:Rotating-wall vessels, promising bioreactors for osteoblastic cell culture: comparison with other 3D conditions. 1019 39

To measure the physiological changes in bone in response to strenuous exercise we performed a prospective study of male army recruits over 10 weeks of basic training. Measurements performed at the start and completion of training consisted of ultrasound (US) measurements of the heel: velocity of sound (VOS in m/seconds) and broadband ultrasound attenuation (BUA in dB/MHz) and bone turnover markers; osteocalcin (OC), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP). Forty subjects were recruited for the study and 26 completed training. Over the 10-week study period there was a significant 1.7% fall in mean VOS [mean paired difference (mpd) 27.2 m/second, SEM 9.5 (95% CI 7.5-46.8) P = 0.009] and a nonsignificant 3.4% increase in BUA (P = 0.159). There were significant falls in markers of bone formation OC [11.6%, mpd 0. 11 microg/liter (95% CI 0.07-0.14) P < 0.001] and BALP [13.3%, mpd 3. 49 U/liter (CI 0.80-6.18) P = 0.013] and a nonsignificant 9.5% fall in TRAP a marker of bone resorption. The 10 recruits subsequently injured had a significantly lower VOS on entry [mean difference 24.2 m/seconds (95% CI 4.6-43.7) P = 0.017] and nonsignificantly raised BUA and baseline levels of all bone markers. The ultrasound changes may be accounted for by increase in trabecular separation and a fall in trabecular connectivity due to microfracture. The decrease in bone markers implies a fall in bone turnover.
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PMID:The effects of 10 weeks military training on heel ultrasound and bone turnover. 1020 15

The impact of estrogen deficiency on bone has been extensively studied in the female; however, the effects of androgen deficiency on calcium fluxes in males have been less well characterized. We investigated the effect of short-term, severe androgen deficiency on measures of calcium absorption and kinetics as well as on markers of bone turnover in males. To accomplish this, 11 healthy male volunteers were recruited (mean age 23.3 +/- 0.5 years [SEM], body mass index 25.3 +/- 0.8 kg/m2). They consumed a weight maintenance diet for at least 3 days prior to admission to our Research Unit, with a calcium intake of approximately 1200 mg/day. At baseline (D1), subjects received 42Ca intravenously as well as 44Ca PO mixed with milk or juice. A 29-h urine collection was begun and blood samples collected at frequent intervals for the measurement of the isotopic enrichment of 42Ca and 44Ca using thermal ionization mass spectrometry. Twice daily urine samples were collected for 5 days after the administration of the isotopes. A gonadotropin-releasing hormone agonist (Lupron) was given after D1, again 3 weeks later, and studies repeated identically 4 weeks (D2, n = 6) and 10 weeks from baseline (D3, n = 7) (two subjects completed three studies). Testosterone concentrations were markedly suppressed on both D2 and D3 (-95%, p < 0.006), whereas there were no detectable changes in growth hormone and insulin-like growth factor-1 concentrations. Urinary calcium excretion increased significantly after 4 weeks (43%, p = 0.0007) and 10 weeks (73%, p = 0.003) of sustained hypogonadism. Using a multicompartmental kinetic model, the contribution of oral calcium to the urinary losses was decreased by D3 (-41%, p = 0.01), yet the contribution of bone calcium to urine losses increased by 10 weeks (+11%, p = 0.01). There was a 21% decrease in bone calcium deposition (Vo+) by D3 (p < 0.05) with no significant change in bone resorption rates (Vo-). There was a significant correlation between the decrease in testosterone concentration and the increase in urinary calcium excretion, especially at 10 weeks (R2 = 0.84, p = 0.004). These kinetic changes were accompanied by a decrease in osteocalcin concentrations on D2, with improvements by D3. Urinary N telopeptide, a measure of bone resorption, also increased during the studies. In summary, profound hypogonadism in young males is associated with marked increases in urinary calcium losses, with a greater contribution of bone calcium to those losses and decreased kinetic markers of bone calcium deposition. We conclude that even short-term, severe deficiency in gonadal steroids can have profound negative effects on calcium and bone metabolism in males.
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PMID:Profound hypogonadism has significant negative effects on calcium balance in males: a calcium kinetic study. 1023 79

The biocompatibility of silicon nitride (Si3N4) was assessed in an in vitro model using the human osteoblast-like MG-63 cell line. Cells were propagated on the surface of: reaction-bonded silicon nitride discs, sintered after reaction-bonded silicon nitride discs or control polystyrene surface for 48 h. Compared to cells propagated on polystyrene surface, cells grown on the surface of unpolished silicon nitride discs had significantly lower cell yield and decreased osteocalcin production. In contrast, cells on the surface of polished silicon nitride discs showed similar proliferative capacity to control cells propagated on polystyrene surface. Cells propagated on polished discs also produced higher levels of osteocalcin than cells on unpolished discs. SEM analysis showed cells with well-delineated morphology and cytoplasmic extensions when propagated on polished sintered after reaction-bonded discs. Cells appeared more spherical, when grown on polished reaction-bonded discs. The results of this study suggest that silicon nitride is a non-toxic, biocompatible ceramic surface for the propagation of functional human bone cells in vitro. Its high wear resistance and ability to support bone cell growth and metabolism make silicone nitride an attractive candidate for clinical application. Further studies are needed to explore the feasibility of using silicon nitride clinically as an orthopedic biomaterial.
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PMID:Enhanced proliferation and osteocalcin production by human osteoblast-like MG63 cells on silicon nitride ceramic discs. 1039 88

A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17beta-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1-4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7% +/- 0.7% with estradiol 25 mg/day, 7.3% +/- 0.7% with estradiol 50 mg/day and 8.7% +/- 0.7% with estradiol 75 mg/day (all values mean +/- SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25-75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses.
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PMID:Matrix delivery transdermal 17beta-estradiol for the prevention of bone loss in postmenopausal women. The International Study Group. 1055 Apr 54

Selective estrogen receptor modulators (SERMs) can prevent the bone loss induced by ovariectomy (OVX), but it is not established whether they can increase bone mass and strength in a curative protocol in ovariectomized osteopenic animals. We investigated the influence of a SERM of the new generation, MDL 103,323, on areal bone mineral density (BMD), as measured by dual-energy X-ray absorptiometry, bone strength and remodeling in OVX osteopenic rats. Nine weeks after OVX, 8-month-old rats were divided into six groups of 10 animals. MDL 103,323 was given by gavage at doses of 0.01, 0.1 or 0.6 mg/kg body weight, 5 days a week. The effect of MDL 103,323 was compared with that of the bisphosphonate pamidronate (APD), which was injected subcutaneously at a dose of 1.6 mmol/kg body weight for 5 days every 4 weeks. Lumbar spine (LS), femoral neck (FN), proximal tibia (PT) and midshaft tibia (MT) BMD, bone strength, and proximal tibia histomorphometry, serum osteocalcin, urinary total deoxypyridinoline and serum insulin-like growth factor I (IGF-I) were measured. After 16 weeks of treatment, BMD changes (means +/- SEM) were -11.4 +/- 2. 2, +4.0 +/- 2.1 and +6.4 +/- 1.0% respectively in OVX controls, in rats treated with 0.1 mg/kg MDL 103,323 (p<0.05) and in APD-treated rats (p<0.02) at the level of LS; -0.4 +/- 1.1, +6.7 +/- 1.4, +7.2 +/- 1.8% (p<0.01 and NS) at the level of FN; and -2.6 +/- 1.2%, +5.8 +/- 1.2, +6.9 +/- 1.4% (p<0.03 and 0.01) at the level of PT. MDL 103, 323-treated animals had a higher trabecular bone volume, a higher number of trabeculae and smaller intertrabecular spaces compared with OVX controls. Vertebral body ultimate strength was 186 +/- 13, 292 +/- 16, 249 +/- 23 N (p<0.05) in OVX controls, MDL 103, 323-treated rats and APD-treated rats, respectively. The administration of 0.6 mg/kg of MDL 103,323 did not further increase BMD or bone strength, indicating a bell-shaped dose-response curve. MDL 103,323 lowered plasma osteocalcin concentration and urinary deoxypyridinoline excretion. In rats treated with 0.1 mg/kg MDL 103, 323, plasma IGF-I was increased as compared with OVX controls (664 +/- 36 ng/ml vs 527 +/- 39 ng/ml, p<0.05). In conclusion, these results indicate that this new SERM positively influences BMD and lumbar spine bone strength in estrogen-deficient rats.
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PMID:The new selective estrogen receptor modulator MDL 103,323 increases bone mineral density and bone strength in adult ovariectomized rats. 1059 34


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