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Biomedical subjects

L Raisz

Publications and source records attributed to L Raisz.

5 recordsLinked to original sources
PubMed2000

Short-term risedronate treatment in postmenopausal women: effects on biochemical markers of bone turnover.

The development of new biochemical markers has made it possible to assess the effects of therapeutic agents on bone turnover more rapidly and precisely. In this early phase II study, we analyzed the effects of short-term, high-dose treatment with risedronate, a potent pyridinyl bisphosphonate, on markers of bone resorption and formation. Resorption markers included urinary free deoxypyridinoline (D-Pyr) crosslinks, N-terminal telopeptide (NTx) and C-terminal telopeptide (CTx) type I collagen crosslinks. Bone formation markers included osteocalcin (OC), bone-specific alkaline phosphatase (BSAP) and the C-terminal peptide of type I procollagen (PICP). All three resorption markers showed rapid, significant (p<0.05) decreases from baseline following daily administration of 30 mg risedronate for 2 weeks. The mean decreases at 2 weeks were 28% for D-Pyr, 61% for NTx and 73% for CTx, respectively. Over the next 10 weeks after treatment, D-Pyr approached baseline while NTx and CTx remained well below baseline values. The markers of bone formation showed little change during therapy but decreased significantly at 4-10 weeks after therapy - an expected outcome of bisphosphonate therapy. Moreover, there was a significant correlation between the early effects on bone resorption markers and the delayed effects on formation markers. This study demonstrates that the approved dose of risedonate (30 mg/day) for Paget's disease is effective at decreasing bone turnover after 2 weeks of treatment, as observed by the sensitive response of bone turnover markers.

Alkaline Phosphatase↗
PubMed1999

Potential biochemical growth markers in premature infants.

Identification of a biochemical marker of growth in low birth weight (LBW) infants would be of benefit to rapidly assess the effects of illness and/or therapeutic intervention. The aims of the present study were (1) to measure serially the C-terminal fragment of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) in LBW infants during the first 6 weeks of life; (2) to correlate the changes in PICP, BSAP, and OC with the changes in weight; and (3) to evaluate PICP levels as a marker for bronchopulmonary dysplasia (BPD). Premature neonates (< or =36 weeks of gestation) had cord blood and then weekly blood samples taken from up to 6 weeks after birth. Daily changes in weight were recorded. Measurements of serum PICP, BSAP, and OC were done in duplicate by immunoassay. In a subset population (25-30 weeks), PICP levels in the first 4 weeks of life were evaluated as a marker for subsequent development of BPD. A total of 77 infants had serum PICP and BSAP measured. The mean (+/- SEM) gestational ages of all the infants were 30.4 (+/-0.3) weeks and birth weights 1477 (+/-55) g. Fifteen infants also had measurements of OC done. In these 15 infants, change in weight was correlated significantly with PICP (p<0.0001), but not with either BSAP (p = 0.8) or OC measurements (p = 0.9). In appropriate for gestational age (AGA) infants (n = 66), the PICP values decreased from the cord blood values to the week 1 measurement, coinciding with the fall in weight over the same time period. BSAP values, on the other hand, continued to increase from birth onwards. Over the first 6 weeks of postnatal life in these infants, change in weight had a stronger positive correlation with PICP (R2 = 0.43, p<0.0001) than BSAP (R2 = 0.03, p<0.01). In the subset population, PICP levels at week 4 were significantly lower (p<0.04) in those infants who subsequently developed BPD. PICP measurements are correlated with somatic growth in premature infants and could be used as a biochemical marker in infants who develop BPD.

Alkaline Phosphatase↗
PubMed1997

Transforming growth factor-beta1 regulation of prostaglandin G/H synthase-2 expression in osteoblastic MC3T3-E1 cells.

Transforming growth factor-beta (TGFbeta) plays an important role in bone development and remodeling. TGFbeta stimulates PGE2 production, enhances interleukin-1-stimulated PGE2 production, and can stimulate PG-mediated bone resorption. We found that TGFbeta induced prostaglandin G/H synthase (PGHS-2) messenger RNA (mRNA) and PGE2 production in neonatal mouse calvarial cultures and in primary cells derived from these calvariae. We used MC3T3-E1 cells, an immortalized osteoblastic cell line derived from mouse calvariae, to examine the mechanism of PGHS-2 induction. PGHS-2 mRNA was rapidly induced by TGFbeta (10 ng/ml) in MC3T3-E1 cells; mRNA levels peaked at 4-8 h and were still elevated at 24 h. Induction of PGHS-2 protein and PGE2 production correlated with PGHS-2 mRNA levels. In contrast, TGFbeta had much less effect on PGHS-1 mRNA levels. Unlike the response to other agonists, PGHS-2 mRNA induction by TGFbeta was not enhanced by cycloheximide pretreatment, suggesting a requirement for new protein synthesis. To study transcriptional regulation, cells were stably transfected with a PGHS-2 promoter-luciferase reporter construct containing 371 bp of the 5'-flanking region and 70 bp of untranslated DNA from the PGHS-2 gene. TGFbeta-stimulated luciferase activity paralleled PGHS-2 mRNA induction. Stimulation of luciferase activity and PGHS-2 mRNA levels by other agonists, including interleukin-1, TGF alpha, forskolin, and phorbol 13-myristate 12-acetate, were enhanced by TGFbeta. A 90% drop in luciferase activity occurred with deletion of the region from -371 to -213 bp of the PGHS-2 promoter. The PG response to TGFbeta in MC3T3-E1 cells appears to be mediated primarily by transcriptional regulation of PGHS-2 expression through one or more cis-acting elements located between -371 and -213 bp in the 5'-flanking region of the PGHS-2 gene.

Animals↗