Biomedical subjects

L T Jensen

Publications and source records attributed to L T Jensen.

At least 37 records · Page 2Linked to original sources

PubMed1996

Enhanced effectiveness of copper ion buffering by CUP1 metallothionein compared with CRS5 metallothionein in Saccharomyces cerevisiae.

The bakers' yeast Saccharomyces cerevisiae contains a metallothionein (MT) gene family comprised of the amplified CUP1 locus and the single copy CRS5 gene. We demonstrate that CUP1 plays the dominant role in copper detoxification. A single copy of CUP1 was far more effective in conferring copper resistance than was CRS5. The CUP1 promoter contributes to this resistance; in a promoter exchange experiment, the Crs5 MT conferred strong copper resistance when its expression was driven by the CUP1 promoter, and conversely, the CRS5 promoter reduced the effectiveness of Cup1 MT. Unlike CUP1, the CRS5 promoter appears to be refractory to high concentrations of copper. The CUP1 coding sequences also contribute to copper tolerance, presumably reflecting the enhanced binding avidity of Cup1 MT for Cu(I) ions. In studies with the bathocuproine Cu(I) chelator, the Cu(I) ions bound to Crs5 were kinetically more labile than the Cu(I) binding to Cup1. Our findings are consistent with the assembly of Crs5 into two metal-binding clusters, similar to mammalian MTs, but unlike Cup1. Overall, the striking differences in gene structure, regulation, and function of CUP1 and CRS5 are remarkably reminiscent of the MTI and MTII genes of the pathogenic yeast Candida glabrata.

Buffers↗

PubMed1996

Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome.

OBJECTIVE: Recombinant IGF-I is now available for the treatment of GH insensitivity (Laron syndrome). We have determined the effects of IGF-I on soft connective tissue and bone metabolism in a group of patients with this disorder. PATIENTS AND DESIGN: Thirteen patients with Laron syndrome (LS) (8 children and 5 adults) were included in the study. The children with LS were treated with IGF-I for 3 years with daily doses of 150-200 micrograms/kg. The adult LS patients were treated for 9 months with daily doses of 50-120 micrograms/kg. Blood samples for procollagens were collected before, during and at the end of IGF-I treatment. MEASUREMENTS: Serum levels of the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and of the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were determined before and during IGF-I administration. RESULTS: Untreated patients with LS had lower than normal serum levels of PICP and PIIINP for age. IGF-I treatment increased significantly the PIIINP levels in children from 7.2 +/- 2.8 (SD) to 12.5 +/- 2.2 micrograms/l (P < 0.001), and in adults from 2.7 +/- 1.0 to 8.4 +/- 3.6 micrograms/l (P < 0.001); serum PICP increased from 243 +/- 123 to 384 +/- 190 micrograms/l (P < 0.087) in children, and in adults from 43.4 +/- 8.1 to 135.8 +/- 41.9 micrograms/l (P < 0.001). ICTP levels in children increased from 9.7 +/- 3.7 to 14.3 +/- 5.9 micrograms/l (P < 0.001) and in adult patients levels increased from 3.6 +/- 0.9 to 5.5 +/- 2.2 micrograms/l (P < 0.001) during treatment and returned to basal values after stopping IGF-I administration. CONCLUSIONS: Low procollagen levels in untreated Laron syndrome patients and their rise during replacement therapy with IGF-I provide evidence that IGF-I plays an important role in bone and soft connective tissue metabolism and that serum procollagen may serve as a marker to reflect some of the biochemical changes induced by IGF-I in connective tissue in the initial periods of treatment.

Adolescent↗

PubMed1996

Analysis of 0.5-kilobase-pair repeats in the Mycoplasma hominis lmp gene system and identification of gene products.

Mycoplasma hominis, an opportunistic pathogenic bacterium of humans, has a small genome of 700 kb. Despite this, multiple copies of gene sequences with similarities to the structural gene (lmp1) of a 135-kDa surface-located membrane protein (Lmp1) have been identified on the genome of M. hominis PG21 (lmp2, lmp3, and lmp4). The distance between the lmp1-lmp2 region and the lmp3-lmp4 region was more than 110 kb. lmp3-lmp4 of M. hominis PG21 was sequenced and found to contain two putative genes. The gene region of 6.5 kb contained a 5' unique region and a 3' unique region separated by 9 0.5-kb repeats with 51 to 90% similarity to 10 similar repeats found in the lmp1-lmp2 region. The 0.5-kb DNA repeats thus comprised about 1% of the entire genome. In both regions, a base change in one of the repeats gave rise to a stop codon, and thereby lmp2 and lmp4 occurred. By PCR amplification of reverse-transcriptase-generated cDNA it was shown that all four genes were transcribed. By use of Lmp-specific antibodies we showed that both lmp1 and lmp3 were translated into proteins (Lmp1 and Lmp3). Each of the four lmp genes represented by their unique cloned segments was used as a probe to analyze the presence, distribution, and organization of the genes within the genome in 13 M. hominis isolates. The repetitive element was detected at one or two locations on the chromosome for all isolates. The lmp3-specific element was present in all isolates, and lmp1- and lmp2-specific elements were present in all but one isolate. The lmp4-specific element was present in about half the isolates tested. For five M. hominis isolates the chromosomal location of the lmp genes was mapped.

Amino Acid Sequence↗

PubMed1996

Long-term effects of intravenous 1 alpha (OH)D3 combined with CaCO3 and low-calcium dialysis on secondary hyperparathyroidism and biochemical bone markers in patients on chronic hemodialysis.

The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l) on plasma (p) parathyroid hormone (PTH) and biochemical bone markers (osteocalcin, alkaline phosphatase, procollagen type 1 c-terminal extension peptide) were examined in 54 patients on chronic hemodialysis with either normal or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood samples were obtained 1 week before the start of treatment and then every 2nd week. 20 patients with initially normal PTH levels (23.5 +/- 4.17 pg/ml) and 34 patients with initially elevated PTH levels (301 +/- 45 pg/ml) were followed for up to 88 weeks. The present investigation: demonstrated: (1) 'Low-calcium hemodialysis' (1.25 mmol/l) made it possible to use larger doses of CaCO3 and to reduce the doses of an aluminium-containing oral phosphate binder. A decrease in p-Ca2+ during dialysis was induced, and special care had to focus on the compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism. (2) The combination of 'low-calcium hemodialysis', CaCO3, and pulse intravenous 1 alpha (OH)D3 prevented the development of secondary hyperparathyroidism in patients with normal PTH levels and induced a long-term suppression of p-PTH (106 +/- 25 pg/ml, 88 weeks) in the patients with secondary hyperparathyroidism. By careful monitoring, severe hypercalcemia and hyperphosphatemia were avoided. There were no indications, clinically or biochemically, of development of adynamic bone disease. (3) Bone lesions were healed and a decrease of the bone mineral content in lumbar spine and femoral neck of patients with both normal and elevated PTH levels prevented. (4) The present results may suggest that PTH might be of influence on that regulation of procollagen type 1 c-terminal extension peptide.

Adult↗

PubMed1995

The aminoterminal propeptide of type III procollagen provides new information on prognosis after acute myocardial infarction.

The aim of the study was to examine sequential changes in serum levels of the aminoterminal propeptide of type III procollagen (S-PIIINP) after acute myocardial infarction (AMI), and to assess the value of S-PIIINP as a predictor of outcome. The study group comprised 74 patients with AMI, and 24 patients in whom AMI was suspected but disproved. S-PIIINP changed characteristically after AMI, and in patients not receiving thrombolytic therapy or having cardiogenic shock, the changes correlated to peak enzyme values (r = 0.4, p < or = 0.03). S-PIIINP was higher at days 0 to 2 in nonsurviving AMI patients than in survivors (p < 0.05). With use of either the upper quartile for S-PIIINP at day 0 for nonsurviving AMI patients or the mean value of S-PIIINP in a normal population plus 2 SDs as a cutoff, the predictive value of a negative test ranged from 0.79 to 0.87 at days 0 to 2, and the predictive value of a positive test ranged from 0.39 to 0.67. Thus, S-PIIINP on admission and for the following few days after AMI is higher in patients with poor outcome.

Adult↗

PubMed1995

Bioactivity of metallothionein-3 correlates with its novel beta domain sequence rather than metal binding properties.

Human and mouse metallothionein-3 (MT-3) molecules exhibit the same metal binding stoichiometry with Zn(II), Cd(II), or Cu(I) as MT-1 or MT-2 molecules, suggesting that MT-3 consists of two domains enfolding separate polymetallic clusters. The kinetic reactivities of Zn(II) complexes of MT-3 with the chelator ethylenediaminetetraacetic acid (EDTA) or the thiol reagent dithiobis(2-nitrobenzoic acid) (DTNB) resembles the reactivity of ZnMT-1. Furthermore, the candidate alpha and beta domain peptides of human MT-3 are very similar to MT-1 domain peptides in the reactivity of Zn(II) complexes. Zn(II) complexes of human and mouse MT-3 inhibit the survival of rat cortical neurons cultured in the presence of an Alzheimer's disease brain extract. Inhibitory activity is unique to the MT-3 isoform and is a property of the N-terminal beta domain. The inhibitory activity of the 32-residue MT-3 beta domain is abolished by a double mutation within the beta domain resulting in the conversion of the C-P-C-P sequence to either C-S-C-A or C-T-C-T. Thus, the bioactivity arises from a novel structure of the N-terminal beta domain of MT-3 and not any unusual metal-binding properties.

Amino Acid Sequence↗

PubMed1995

Effect on collagen metabolism of thrombolytic therapy with tissue-plasminogen activator. A randomized, placebo-controlled study.

This paper assesses alterations in collagen metabolism following thrombolytic therapy of acute myocardial infarction with tissue-plasminogen activator. Sequential serum measurements of the amino-terminal propeptide of type III procollagen (S-PIIINP) and the carboxyterminal propeptide of type I collagen (S-PICP) in patients suspected of acute myocardial infarction randomized to tissue-plasminogen activator or placebo were used. S-PIIINP increased at 3 h in patients with acute myocardial infarction treated with tissue-plasminogen activator (P < 0.05). S-PIIINP was higher in patients treated with tissue-plasminogen activator compared with placebo-treated patients at 3 and 6 h (P < 0.05). S-PICP decreased independently of therapy and diagnosis. Tissue-plasminogen activator, therefore, induces breakdown of collagen, some of which is located in the wall of atheromatous arteries. Vascular patency following thrombolytic therapy may partly be mediated by breakdown of thrombogenic collagen in the vessel wall. The findings may suggest a role for S-PIIINP as a non-invasive indicator of the risk of reocclusion.

Adolescent↗

PubMed1995

A 135-kilodalton surface antigen of Mycoplasma hominis PG21 contains multiple directly repeated sequences.

A monoclonal antibody was used to characterize a 135-kDa surface-located membrane protein (Lmp1) generally present in Mycoplasma hominis strains. The monoclonal antibody, 552, was applied to identify the corresponding gene in an expression library of M. hominis PG21 DNA. The M. hominis PG21 lmp1 gene was sequenced, and its gene product was characterized with the goal of elucidating the structure and function of Lmp1. A total of 7,196 bp in the lmp1 region was sequenced. An open reading frame of 4,032 bp, encoding a protein of 1,344 amino acids with a calculated molecular weight of 147,000, was identified. Analysis of the deduced amino acid sequence predicted a hydrophilic protein with a basic pI (10.0). The N-terminal 24 amino acids were a typical leader sequence. Downstream from the first 726 nucleotides, six similar direct repeats of 471 nucleotides were found. In repeat 7, a single-base substitution, C-->A, gave rise to the stop codon of lmp1. Thus, the C-terminal 945 amino acids were encoded by the 471-bp direct repeats. As evidenced by Southern blot analysis, the gene encoding the 135-kDa antigen is part of a multigene family. One of the genes, lmp2, was situated directly downstream from lmp1 where the direct repeats continued.

Amino Acid Sequence↗

PubMed1995

Selection of Mycoplasma hominis PG21 deletion mutants by cultivation in the presence of monoclonal antibody 552.

Three mutants of Mycoplasma hominis PG21 were isolated and shown to contain alterations in the size of a repeat-containing gene encoding a surface-localized 135-kDa antigen designated Lmp1. The mutants were isolated by cultivating M. hominis for a 3-month period in the presence of Lmp1-specific monoclonal antibody (MAb) 552. The epitope for MAb 552 was localized at the repeated part of the protein. The gene encoding Lmp1 is part of a transcriptional complex that contains 9.5 direct repeats of 471 bp each. Pure cultures of mutant strains were obtained by subcloning, and three mutants were characterized. The mutants showed deletions of a various number of repeats. The deletions were accompanied by a decrease in size of the proteins. With increasing size of deletions, agglutination and growth inhibition by MAb 552 became less pronounced. Spontaneous aggregation of the mutant M. hominis cells in culture medium was, however, increased, indicating that the repeated elements may be of importance for repulsion of the cells.

Agglutination Tests↗

PubMed1995

Collagen derived serum markers in carcinoma of the prostate.

Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p < 0.05). The level of PIIINP, ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p < 0.0001). All variables showed a significant positive relationship with alkaline phosphatase. The sensitivity ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68, respectively.

Aged↗

PubMed1995

Collagen markers in peritoneal dialysis patients.

Possible relationships between the dialysate-to-plasma creatinine equilibration ratio (D/Pcreatinine 4 hour), duration of peritoneal dialysis treatment, number of peritonitis episodes, and mass appearance rates of three connective tissue markers [carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type III procollagen (PIIINP), and carboxyterminal telopeptide of type I collagen (ICTP)] were studied in 19 nondiabetic peritoneal dialysis patients. The absence of correlation between the mass appearance rates of the markers and the duration of dialysis treatment as well as the number of peritonitis episodes supports the concept that peritoneal dialysis does not cause persistent changes in the deposition and degradation rates of collagen. A correlation between the D/Pcreatinine 4 hr and the PICP mass appearance rates was found. Since it is unlikely that transperitoneal transport alone is responsible for the appearance of PICP in dialysate, this might reflect an association between a large peritoneal surface area and the amount of submesothelial connective tissue.

Adult↗

PubMed1995

Collagen metabolism in obesity: the effect of weight loss.

OBJECTIVE: To investigate the impact of obesity, fat distribution and weight loss on collagen turnover using serum concentrations of the carboxyterminal propeptide of type I procollagen (S-PICP) and the aminoterminal propeptide of type III pro-collagen (S-PIIINP) as markers for collagen turnover. DESIGN: Blood samples were obtained once at baseline, and after 8 and 16 weeks of dietary treatment (5.0 MJ/day diet). SETTING: Outpatient clinic of Hvidovre University Hospital. MAIN OUTCOME MEASURES: S-PICP, S-PIIINP, fat distribution and weight loss. RESULTS: S-PIIINP was associated with body weight (r = 0.37; P = 0.004), height (r = 0.27; P = 0.04), waist circumference (r = 0.35; P = 0.007), as well as with WHR (r = 0.33; P = 0.01) and was inversely correlated to age (r = -0.40; P = 0.002). Compared with randomly selected controls from a large pool of healthy volunteers, the obese patients had elevated S-PIIINP values before as well as during weight loss, whereas S-PICP levels were within the normal range and did not correlate with any anthropometric measures. The average weight loss after 16 weeks dietary treatment was 8.1 kg (s.d. = 0.8). S-PIIINP decreased during the 16 weeks of energy restriction (P < 0.05) and changes in S-PIIINP was correlated to body weight loss (r = 0.32; P < 0.05) and to changes in waist circumference (r = 0.34; P < 0.05) as well as changes in WHR (r = 0.30; P < 0.05). CONCLUSION: S-PIIINP is elevated in obesity and associated with body fat distribution, suggesting an increased turnover of type III collagen related to obesity in general and to abdominal obesity in particular. S-PIIINP levels decreases during weight loss in obese subjects, whereas S-PICP levels seems un-related to obesity and weight loss.

Adult↗

PubMed1995

Type I procollagen propeptide in patients on CAPD: its relationships with bone histology, osteocalcin, and parathyroid hormone.

Serum procollagen type I carboxyterminal propeptide (PICP) has been shown to be a useful marker of bone formation in patients undergoing haemodialysis. However, PICP levels has not been evaluated in depth in patients maintained on continuous ambulatory peritoneal dialysis (CAPD). Therefore serum and dialysate levels of PICP, its peritoneal clearance (Clp), mass transfer (MTp), and its possible relationship with osteocalcin, parathyroid hormone (PTH), and bone histomorphometry were studied in a group of CAPD patients. Serum PICP was just above the normal range with significant amounts detected in the dialysate but no correlations were found between levels of serum PICP, dialysate PICP, and Clp-PICP. One patient with systemic lupus and osteitis fibrosa had extraordinarily high serum and dialysate levels of PICP. The patient later developed sclerosing peritonitis. No associations were seen between serum PICP and Clp-PICP and any of the 18 bone histomorphometric parameters evaluated. Dialysate level of PICP correlated negatively with mineral appositional rate (r = -0.62, P < 0.01) and mineralization lag time (r = 0.64, P < 0.01). MTp-PICP correlated positively with mineral appositional rate (r = 0.65, P < 0.01). Serum osteocalcin and serum PTH levels did not correlate to serum, dialysate, Clp or MTp measurements of PICP. These results suggest that measurements of PICP in CAPD patients do not give substantial information as an non-invasive marker of bone histology.

Adult↗

PubMed1994

Dominance of metallothionein in metal ion buffering in yeast capable of synthesis of (gamma EC)nG isopeptides.

The relationship of yeast metallothionein (MT) and (gamma EC)nG isopeptides (phytochelatins) in metal ion buffering was assessed. The effect of constitutive expression of yeast metallothionein (MT) genes on accumulation of metal-(gamma EC)nG isopeptide (phytochelatin) complexes was analyzed in Candida glabrata and Schizosaccharomyces pombe cultures incubated in the presence of cadmium salts. Constitutive expression of the Saccharomyces cerevisiae MT (CUP1) gene inhibited the accumulation of metal-phytochelatin complexes in both C. glabrata and S. pombe. Intracellular Cd(II) sequestration occurred by formation of CdMT complexes. Phytochelatin (gamma EC)nG complexes appear to function in metal buffering in cells when MT genes are not present or expressed. A third condition in which metal-(gamma EC)nG complexes are observed is when constitutively expressed MT does not accumulate. We observed that C. glabrata lacking the AMT1 gene necessary for copper induction of the MT genes expressed MTII constitutively, but this expression does not lead to CdMTII accumulation. Only Cd-(gamma EC)nG complexes accumulate. Likewise, metal exposed cultures of S. cerevisiae (cup1) transformed with C. glabrata MTII under the constitutive ADH1 promoter resulted in constitutive expression of MTII and accumulation of CuMTII complexes but no CdMTII complexes. The inability of constitutively expressed C. glabrata MTII to buffer Cd(II) ions may arise in part from an inherent kinetic lability of CdMTII complexes. Incubation of ZnMTII with a metallochromic chelator, 4-(2-pyridylazo)resorcinol resulted in greater Zn(II) loss than Zn(II) complexes with CUP1 MT and C. glabrata MTI. C. glabrata MTII appears to be the first MT described which forms an unstable Cd(II) complex.

Binding Sites↗

PubMed1994

Enhanced neurotrophic activity in Alzheimer's disease cortex is not associated with down-regulation of metallothionein-III (GIF).

Alzheimer's disease (AD) is a chronic neurodegenerative disorder for which the pathogenic mechanisms are not well understood. Previous studies demonstrated that extracts prepared from AD brains could increase the survival of rat cortical neurons in vitro. Additional studies indicated that this enhanced neurotrophic activity of AD brain was due to a reduction of a growth inhibitory factor (GIF) that was subsequently shown to be a new member of the metallothionein (MT) gene family, and designated MT-III. The study presented here examined the association between neurotrophic activity and MT-III expression in frontal cortices from eight AD and five control brains, and further characterized the inhibitory activity of MT-III. On average, AD extracts stimulated the survival of approximately 2-fold more rat cortical neurons than control extracts, demonstrating that AD brain possesses elevated neurotrophic activity. When recombinant MTs were added to cultures grown in the presence of brain extract, MT-III but not MT-I had an inhibitory effect on neuron survival, confirming that MT-III is a specific inhibitory factor in this assay. However, in contrast to previous reports, neither MT-III mRNA nor MT-III protein levels were significantly decreased in the AD group. Therefore, the difference in neurotrophic activity between the AD and control brain samples examined in this study is probably not directly mediated by MT-III. These results suggest that MT-III down-regulation is not an important pathogenic event in some cases of AD.

Alzheimer Disease↗

PubMed1994

The carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen in serum as a marker of bone resorption: the effect of nandrolone decanoate and hormone replacement therapy.

Carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) in serum has recently been proposed as a new biochemical marker of bone resorption. In the present study we compared serum ICTP with radiopharmaceutical and histomorphometric measurements of bone turnover in postmenopausal women with mild osteoporosis, and assessed the effect of hormone replacement therapy (HRT) (2 mg 17 beta-estradiol plus 1 mg norethisterone daily) and anabolic steroid therapy (50 mg nandrolone decanoate (ND) i.m. every 3 weeks) on serum ICTP in two double-blind placebo-controlled studies with 55 to 75-year-old women. Serum ICTP measured by radioimmunoassay (RIA) correlated significantly with the 24-hour whole body retention of 99m-technetium diphosphonate (Rho = 0.47, P < 0.001, n = 66), but not with histomorphometric measurements of bone turnover in iliac crest biopsies. One year of HRT (n = 16) versus placebo (n = 15) did not produce significant changes in serum ICTP. Compared with placebo (n = 17), 1 year of ND (n = 19) produced an increase in serum ICTP of 90 +/- 16% (P < 0.0001); 6 months after discontinuation of the treatment, serum ICTP had returned to pretreatment values. We conclude that serum ICTP does reflect bone metabolism in postmenopausal osteoporosis, but it is not a sensitive marker of the changes in bone resorption induced by hormone replacement therapy, and it does not correspond with other measures of bone resorption during anabolic steroid therapy.

Aged↗

PubMed1994

Collagen turnover after tibial fractures.

Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture. The markers were the carboxy-terminal extension peptide of type I procollagen (PICP), the amino-terminal extension peptide of type III procollagen (PIIINP), and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP). The latter is a new serum marker of degradation of type I collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum after 2 weeks in the diaphyseal fractures and after 6 weeks in the condylar fractures. The degradation of type I collagen increased after 4 days and reached a maximum at 2 weeks in both groups. The interindividual variation was wide. On a group basis, the turnover of types I and III collagen had levelled of within 26 weeks, although some patients had clearly elevated parameters at the end of the observational period. We suggest that delayed healing of tibial diaphyseal fractures is accompanied by an early increase in the turnover of types I and III collagen.

Adult↗

PubMed1994

Acute effect of oral, intraperitoneal, and intravenous 1 alpha-hydroxycholecalciferol on markers of bone metabolism.

OBJECTIVE: To study the acute effect of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) on serum levels of alkaline phosphatase, Ca2+, osteocalcin, parathyroid hormone (PTH), phosphate and type I and III procollagens (PICP and PIIINP respectively) in patients undergoing peritoneal dialysis. Also, 1,25-(OH)2D3 was measured. DESIGN: Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3. MAIN RESULTS: Following oral administration of 1 alpha-OHD3, a decrease in serum alkaline phosphatase was seen when levels at 1 and 6 h were compared to baseline (P < 0.05). Oral and i.v. drug administrations resulted in an increasing trend in serum Ca2+ throughout the study (P < 0.05). Moreover, a difference in serum Ca2+ was found when 24-h levels after oral 1 alpha-OHD3 dose was compared to baseline (P < 0.05). Serum osteocalcin at 12 and 24 h after oral 1 alpha-OHD3 compared to baseline were increased (P < 0.05). Intact PTH followed a circadian rhythm after all three routes of drug delivery. After 24 h, significant decreases of intact PTH were observed in the oral and i.v. group. No changes in serum phosphate and serum PICP levels were observed over time after oral, i.p., and i.v. delivery of 1 alpha-OHD3. However, serum PIIINP following oral and i.p. administration of 1 alpha-OHD3 decreased at 1 and 6 h (P < 0.05). CONCLUSION: Oral and i.v. administration of 1 alpha-OHD3 does influence serum levels of osteocalcin, PTH, and PIIINP: Noticeable is the significant increase in serum osteocalcin after oral administration of 1 alpha-OHD3, the remarkable increase (22.6%) in osteocalcin 24 h after i.v. 1 alpha-OHD3, though not statistically significant, the increase in serum PTH levels 12 h following oral and i.v. doses of 1 alpha-OHD3 and the moderate effect on serum Ca2+ levels.

Administration, Oral↗