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J Risteli

Publications and source records attributed to J Risteli.

At least 91 records · Page 5Linked to original sources
PubMed1998

Comparison of bone resorption markers during hypocalcemia in dairy cows.

This study investigated whether hydroxyproline, deoxypyridinoline, or the carboxyterminal telopeptide of type I collagen could be used as markers to provide evidence of bone resorption during hypocalcemia of dairy cows. Serum concentrations of the amino-terminal propeptide of type III procollagen were also analyzed to study the effect of parturition on type III collagen, which is a component of soft connective tissues. Urine and blood samples were collected on d 1 to 5, on d 9, and d 14 after parturition from 18 cows with symptoms of periparturient paresis (group 1) and 19 healthy control cows without symptoms (group 2). Urine concentrations of hydroxyproline and deoxypyridinoline were measured with a colorimetric assay and an enzyme immunoassay, respectively. Serum concentrations of the amino-terminal propeptide of type III procollagen were measured using a commercially available radioimmunoassay. A radioimmunoassay was developed to analyze serum concentrations of the carboxyterminal telopeptide of bovine type I collagen. The mean corrected urinary hydroxyproline concentrations in group 1 increased from parturition to d 14; concentrations in group 1 were significantly higher for group 2 after d 5. Mean corrected deoxypyridinoline concentrations in urine increased after parturition to reach a peak at d 9, and serum concentrations of the carboxyterminal telopeptide of type I collagen peaked at d 5. However, mean concentrations of deoxypyridinoline and the carboxyterminal telopeptide of type I collagen did not differ significantly between groups. The variation in the behavior of the three markers is likely a reflection of the different phases and aspects of the bone collagen degradation. In conclusion, assays for urinary deoxypyridinoline and serum carboxyterminal telopeptide of type I collagen determinations are useful tools to follow the course of degradation of bone collagen in dairy cows.

Amino Acids↗
PubMed1997

Aggressive breast cancer leads to discrepant serum levels of the type I procollagen propeptides PINP and PICP.

The propeptides PICP and PINP are derived from the synthesis of type I collagen, a major matrix protein of bone and soft tissues. The aim of this cross-sectional study was to investigate their value as indicators of the aggressivity of breast cancer. Serum PINP, PICP, and total alkaline phosphatase were determined from 89 breast cancer patients. Forty had major bone and/or soft tissue metastases with an aggressive disease course: the progressive disease (PD) group. Forty-nine had either none or minor bone and/or soft tissue metastases with a stable clinical course: the stable disease group (SD). The mean value of PINP in the PD group was 7.2 times higher than that in the SD group (276 +/- 79 microg/l versus 38 +/- 3 microg/l, respectively; P = 0.005), whereas PICP mean value was only 1.7 times higher in the PD group (174 +/- 20 microg/l versus 100 +/- 5 microg/l; P = 0.001). The ratio of PICP to PINP was 1.02 +/- 0.07 in the PD group and 3.07 +/- 0.18 in the SD group (P < 0.001). The correlation between PICP and PINP was linear in the SD group and nonlinear in the PD group. The results indicate that high serum PICP and PINP concentrations and a low PICP:PINP ratio are associated with a highly aggressive nature of breast cancer. Determination of PINP, in particular, may be valuable when evaluating the clinical status of a breast cancer patient.

Alkaline Phosphatase↗
PubMed1997

Comparison of three serum assays for bone collagen formation during postmenopausal estrogen-progestin therapy.

Postmenopausal hormone replacement therapy (HRT) lowers the turnover rate of the mineralized bone matrix, the predominant organic component of which is type I collagen. The effect of estrogen on bone metabolism has been monitored by measuring the circulating concentration of the carboxy-terminal propeptide of type I procollagen (PICP), which decreases during HRT. We have recently developed assays for the intact amino-terminal propeptide (PINP) of type I procollagen, a protein set free from the other end of the same gene product. PICP and PINP, both derived from the synthesis of type I collagen, but differing in their further metabolism, were assessed in 47 postmenopausal women, aged 45-66 years, undergoing postmenopausal HRT. Estradiol-gel applied daily was combined to a continuous progestin administered by three different routes. Serum samples obtained before the treatment and 6 and 12 months after its commencement were analyzed for PICP, PINP, PINP Col 1 (assay variant measuring also the degradation product of PINP) and PIIINP (amino-terminal propeptide of type III procollagen). During HRT the circulating concentration of PICP decreased by 20%, that of PINP by 42% and that of PINP Col 1 by 32% in 12 months. The correlation between the two propeptides, which was 0.676 before the treatment, increased to 0.851 in 6 months and to 0.815 in 12 months. The correlations between PINP and PINP Col 1 were 0.872 before the treatment and increased to 0.925 and 0.941 after 6 and 12 months of treatment, respectively. The serum concentration of PIIINP, which reflects the turnover of the soft tissue collagens, did not change remarkably. Our findings indicate that the intact PINP is a more dynamic marker of bone metabolism than PICP and can therefore be recommended as a marker reflecting the effect of estrogen on bone collagen formation during HRT.

Aged↗
PubMed1997

Collagen scar formation after acute myocardial infarction: relationships to infarct size, left ventricular function, and coronary artery patency.

BACKGROUND: Left ventricular function after acute myocardial infarction (AMI) is determined by the expansion of the infarct zone and remodeling of the noninfarcted myocardium. An occluded infarct-related artery (IRA) is an independent risk factor for remodeling. METHODS AND RESULTS: Changes in myocardial collagen metabolism were evaluated in 36 patients with suspected AMI. The plasma creatine kinase MB fraction and myoglobin release curves were analyzed for assessment of early reperfusion and infarct size. Collagen scar formation was evaluated by measurement of serum concentrations of the aminoterminal propeptide of type III procollagen (PIIINP), the aminoterminal propeptide of type I procollagen (intact PINP), and the carboxyterminal propeptide of type I procollagen (PICP). Plasma renin activity and urine excretion of cortisol and aldosterone were also measured. Coronary angiography and left ventricular cineangiography were performed during early hospitalization. The serum concentration of PIIINP increased from 3.50+/-0.20 to a maximum of 5.08+/-0.36 microg/L (n=32) in the patients with AMI, whereas the concentrations of intact PINP and PICP tended to decrease. The area under the curve (AUC) of PIIINP during the first 10 postinfarction days was larger in patients with severe heart failure or ejection fractions < or = 40% than in those with no heart failure or with an ejection fraction > 40% (P<.05 and P<.01, respectively), and it was also larger in the patients with TIMI grade 0 to 2 flows than in those with TIMI 3 flows (P<.05), despite similar enzymatically determined infarct sizes. No significant correlations between PIIINP and neurohumoral parameters were observed. The AUC of PIIINP and the change in PIIINP during the first 4 days were significantly correlated with indices of cardiac function. CONCLUSIONS: Collagen scar formation after AMI can be quantified by measurement of serum PIIINP concentrations. Scar formation is more prominent in large infarctions causing left ventricular dysfunction and in patients with occluded IRAs.

Adult↗
PubMed1997

Low synthesis rate of type I procollagen is normalized during active back rehabilitation.

STUDY DESIGN: Open, prospective trial with patients participating in an active back restoration program. OBJECTIVES: To compare the concentrations of biochemical indicators of Type I and III collagen synthesis and Type I collagen degradation in the serum of patients with chronic low back pain and healthy control subjects and to evaluate the effect of active back rehabilitation based on vigorous exercise on collagen metabolism. SUMMARY OF BACKGROUND DATA: The aim of active back rehabilitation is to restore the physical function of low back pain patients falling into the so-called "deconditioning syndrome." The changes in functional muscle strength measurements during the restoration rehabilitation program always depend on motivation, learning phenomena, and fear of pain and injury, so that even more objective ways of showing changes in physical activity are needed. METHODS: Specific radioimmunoassays for the amino-terminal (PINP) and carboxy-terminal (PICP) propeptides of Type I procollagen, the amino-terminal propeptide of Type III procollagen (PIIINP), and the cross-linked carboxy-terminal telopeptide of Type I collagen (ICTP) were used for serum samples obtained from 41 patients before, during, and after an active back restoration program and from 16 age- and sex-matched healthy control subjects. RESULTS: The circulating concentrations of PINP and PICP were initially lower in the patients ([mean +/- SD] 35.3 +/- 12.5 micrograms/L and 119.0 +/- 32.6 micrograms/L, respectively) than in the control subjects (47.9 +/- 18.0 micrograms/L and 136.7 +/- 47.7 micrograms/L, respectively; P < 0.05 for PINP). Toward the end of the active back rehabilitation program, both PINP and PICP increased in the patients (P < 0.001 for the increase between the initial level and the end of rehabilitation). There was a significant difference in the time courses of these changes, with the circulating PICP concentration increasing earlier than that of PINP. In the intervention group, the PIIINP concentration also increased (P < 0.01), whereas the ICTP concentration remained unchanged, with a tendency to decrease. No changes occurred in the control subjects. CONCLUSIONS: Active back rehabilitation based on vigorous exercise increases. Type I collagen synthesis in patients with chronic low back pain; this may provide a means of objectively verifying the effects of such rehabilitation.

Adult↗
PubMed1997

Elevated collagen turnover in Nigerian children with calcium-deficiency rickets.

Calcium deficiency is a major etiological determinant of rickets in Nigerian children and is accompanied by undermineralization of the developing bone matrix which is composed largely of type I collagen. We have assessed types I and III collagen metabolism by measuring the circulating concentrations of teh N- and C-terminal pro-peptides (intact PINP and PICP) and the C-terminal telopeptide (ICTP) of type I collagen, and the N-terminal pro-peptide (PIIINP) of type III collagen in 94 healthy Nigerian children and in 44 children aged 1-5 years with active calcium-deficiency rickets. In active rickets the mean levels of the four collagen metabolites were approximately twofold higher than in the healthy children, despite a wide variation of individual values. Mean intact PINP was 812 +/- 279 versus 403 +/- 189 microg/liter; PICP was 573 +/- 265 versus 348 +/- 299 microg/liter; PIIINP was 16.8 +/- 8.6 versus 10.8 +/- 3.6 microg/liter, and ICTP was 28.4 +/- 17.2 versus 11.9 +/- 4.1 microg/liter (all P < 0.001), in rachitic and healthy children, respectively. Healthy children younger than 3 years had higher levels of all the collagen metabolites than those between 3 and 5 years (all P < 0.05). Alkaline phosphatase was greater in rickets than in the healthy group (P < 0.001) whereas mean osteocalcin levels were slightly lower (P = 0.009). 1,25(OH)2D correlated with all the collagen propeptides, but not with ICTP in the healthy children. No such correlations were found in rickets, where there was a poor inverse correlation between 1,25(OH)2D and ICTP. These data suggest that collagen turnover is elevated in cases of calcium-deficiency rickets, where vitamin D status is adequate, possibly indicating increased turnover of undermineralized osteoid.

Bone Development↗
PubMed1997

Systemic therapy with estrogen or estrogen with progestin has no effect on skin collagen in postmenopausal women.

OBJECTIVES: To investigate the effect of estrogen alone or combined with progestin on the amount and synthesis of skin collagen in postmenopausal women. METHODS: Forty-three early postmenopausal women were enrolled into this open, non-randomized parallel-groups study. Fifteen women received a continuous oral dose of 2 mg of 17 beta-estradiol and 1 mg of norethisterone acetate daily and 14 women an oral dose of 2 mg estradiol valerate daily. Fourteen subjects served as controls. The histology and type I and III procollagen immunohistochemistry of the skin, skin thickness, the amount of total collagen determined by a colorimetric method and the synthesis of type I and III collagens determined by analysing procollagen propeptides in the suction blister fluid were studied before the treatment and at 6 and 12 months. The proportional area of elastic fibers and the thickness of the epidermis were assessed from the sections obtained before the treatment and at 12 months, with computerized image analysis. RESULTS: Skin thickness, the amount and rate of collagen synthesis, the proportional area of elastic fibers and the thickness of the epidermis were not affected by either 17 beta-estradiol and 1 mg of norethisterone acetate or 2 mg of estradiol valerate. No histological or immunohistological changes were detected in the skin specimens during the 12-month treatment period compared to the baseline or to the skin specimens of the control group. CONCLUSIONS: A 1-year treatment with systemic estrogen alone or combined with progestin does not change the amount of collagen or the rate of collagen synthesis in postmenopausal women.

Administration, Oral↗
PubMed1997

Very low rate of type I collagen synthesis and degradation in newly diagnosed children with acute lymphoblastic leukemia.

In children with acute lymphoblastic leukemia (ALL), the metabolism of type I collagen, the major collagen of bones, may be changed at diagnosis and during early chemotherapy. In the present study, bone formation and degradation rates were evaluated longitudinally in 35 children with ALL, using two serum markers of bone collagen formation: the amino-terminal (PINP) and carboxyterminal (PICP) propeptides; and a marker of degradation: the carboxyterminal telopeptide of type I collagen (ICTP). These serum markers were determined at diagnosis, during induction treatment (at 1, 4, and 6 weeks), and during consolidation treatment (at 8 and 12 weeks). The changes in the serum markers suggested that, at diagnosis, type I collagen turnover (i.e., both synthesis and degradation) was remarkably low. The median serum levels of PINP, PICP, and ICTP were -2.6 SDS (standard deviation score), -1.5 SDS, and -2.5 SDS, respectively. The PICP and PINP levels declined further during the first week of therapy (p < 0.001), whereas the ICTP levels had risen by end of the induction phase (p < 0.05). By the end of the 12 week interval, the concentrations of the formation and degradation markers had returned to normal (p < 0.01). Our findings suggest that ALL is accompanied by low turnover of bone collagen. The abnormalities are at first aggravated, but then corrected, by treatment.

Adolescent↗
PubMed1997

Concomitant i.v. and oral clodronate in the relief of bone pain--a double-blind placebo-controlled study in patients with prostate cancer.

Fifty-seven patients with advanced prostate cancer resistant to first-line hormonal therapy were treated with estramustine and additionally randomized for treatment with clodronate or placebo. Clodronate treatment was started with 5 days intravenous administration (300 mg day[-1]) and followed by oral treatment (1.6 g day[-1]) for 12 months. Skeletal pain relief was only about 10% better in the clodronate than in the placebo group. The results do not support the superiority of combined intravenous and oral treatment with clodronate compared with oral administration only.

Administration, Oral↗
PubMed1997

Effect of hydrocortisone, methylprednisolone aceponate and momethasone furoate on collagen synthesis in human skin in vivo.

BACKGROUND: Topical corticoids decrease de novo collagen synthesis in the human skin. OBJECTIVE: We studied the effect of three corticoids, hydrocortisone (HC), methylprednisolone aceponate (MPA) and momethasone furoate (MMF) on the de novo synthesis of type I and III collagens. METHODS: Fifteen healthy male volunteers treated four areas marked on their abdominal skin for 1 week. HC was applied twice a day, MPA and MMF once a day plus vehicle once a day and vehicle twice a day. After the treatment, suction blisters were induced on the treated areas, the suction blister fluid (SBF) was collected and procollagen propeptides of type I and III procollagens (PINP, PIIINP, respectively) were analyzed by radioimmunological assays. The protein concentration in SBF was determined by a colorimetric method. RESULTS: All the corticoids studied decreased the procollagen propeptide concentrations in SBF. HC decreased PINP concentration by 66%, MPA by 68% and MMF by 72%. HC decreased PIIINP by 62%, MPA by 68% and MMF by 72%. The protein concentration in SBF was decreased by 11-15% by these topical corticoids. CONCLUSION: HC decreases the concentration of procollagen propeptides in human skin in males to nearly the same extent as MPA and MMF.

Administration, Topical↗
PubMed1997

Propeptide levels of type III and type I procollagen in the serum and bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis.

No single test is available to reliably assess the activity or prognosis of pulmonary sarcoidosis. In this study, we have evaluated two procollagen markers, aminoterminal propeptide of type III procollagen (PIIINP) and carboxyterminal propeptide of type I procollagen (PICP) in serum and bronchoalveolar lavage fluid (BALF) and compared them to other disease markers of pulmonary sarcoidosis, such as serum level of angiotensin converting enzyme (S-ACE) or serum interleukin-2 receptor (S-IL-2R). Bronchoalveolar lavage was performed in 40 sarcoidosis patients without (stages 0-I) and 20 patients with lung parenchymal involvement (stages II-III), as well as in 17 controls. Serum (S)- and BALF-PIIINP and PICP, S-ACE, S-IL-2R, BALF-albumin, BALF-lymphocytes and mast cells were determined in these patients. BALF-PIIINP was clearly and S-PIIINP slightly elevated in sarcoidosis compared to the controls. Similarly BALF-PICP, but not S-PICP, was significantly higher in sarcoidosis. BALF-PIIINP, but not BALF-PICP correlated with S-ACE and S-IL-2R levels. Patients with lung parenchymal disease had higher S-ACE and BALF-PIIINP, but neither S-IL-2R, S-PIIINP nor S- or BALF-PICP were elevated. S-PIIINP and S-IL-2R but not S-ACE were higher in symptomatic than nonsymptomatic patients. Symptomatic patients with parenchymal disease had elevated BALF-PIIINP whereas in the symptomatic nonparenchymal group S-PIIINP was elevated. In conclusion, this is the first study to evaluate carboxyterminal propeptide of type I procollagen in sarcoidosis and showed elevated levels in bronchoalveolar lavage fluid. In contrast to the levels of bronchoalveolar lavage fluid aminoterminal propeptide of type III procollagen, levels of carboxyterminal propeptide of type I procollagen did not correlate with serum level of angiotensin converting enzyme and serum interleukin-2 receptor levels, suggesting that carboxyterminal propeptide of type I procollagen may be less suitable disease marker in sarcoidosis than aminoterminal propeptide of type III procollagen. However, the role of carboxyterminal propeptide of type I procollagen as an indicator of fibrogenesis must be further studied.

Adult↗
PubMed1997

Collagen metabolites in the prediction of response to GH therapy in short children.

To evaluate the role of collagen metabolites in the prediction of the response to GH treatment we measured the serum concentrations of the C-terminal propeptide of type I procollagen (PICP) and the N-terminal propeptide of type III procollagen (PIIINP) with specific RIAs in 35 short children (16 boys) before and after 5 days, 5 weeks and 3 months of GH therapy. The mean age of the children was 10.3 years (range 1.9-16.4 years) and the bone age ranged from 1.2 to 12.5 years (mean 7.6 years). The initial mean relative height (RH) was -3.6 SDS (range -6.6 to -2.4 S.D.). Nineteen children were found to have GH deficiency (GHD; peak GH responses in two pharmacological tests < 10 micrograms/l), while the remaining 16 were considered to have undefined short stature (USS). The children were treated with recombinant human GH (0.1 U/kg given subcutaneously at bedtime 6-7 times/week). The increases in RHI over the first 6 and 12 months of therapy were used as response measures. There was already a significant increase (P < 0.001) in both the serum PICP and PIIINP levels at 5 days, and the concentrations continued to rise up to 3 months, PICP levels rising less than the PIIINP levels. In the whole group the RHI over 6 months correlated most strongly with the absolute PICP concentrations at 3 months (rS = 0.59; P < 0.05), while the absolute PIIINP concentrations at 3 months showed the strongest relation to the one year RHI (rS = 0.69; P < 0.001). In the GHD group the 6 month RHI was most strongly related to the absolute PICP concentration at 3 months (rS = 0.59; P < 0.05). In the USS group the absolute PICP concentrations at 3 months correlated most strongly with the one year RHI (rS = 0.82; P < 0.01). Significant correlations were also observed between the absolute PIIINP levels at 3 months and the 6 month RHI (rS = 0.60; P < 0.05) and 12 month RHI (rS = 0.76; P < 0.01) in this group. These results show that GH therapy results in an unequivocal increase in circulating concentrations of PICP and PIIINP. The serum PICP and PIIINP concentrations may be of value in the prediction of the long-term response to GH therapy.

Adolescent↗
PubMed1997

Increased levels of type I and III collagen and hyaluronan in scleroderma skin.

The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin of patients. The median value of suction blister PIIINP from the transition zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was localized to the dermis by immunohistochemical techniques. PICP and HA levels in blisters from the transition zone were 87% and 53%, respectively, above the levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from the transition zone were 67% and 63%, respectively, higher than the levels measured in healthy volunteers. In plasma from scleroderma patients levels of PIIINP and HA were 38% and 127% higher, respectively, than in plasma of healthy volunteers. The plasma PICP level was not significantly higher in scleroderma patients. Finally, PICP, PIIINP and HA levels were several times higher in suction blister fluid than in plasma. The data indicate that a fibrogenetic process takes place in the transition zone of scleroderma. The method may be used to monitor the progression of scleroderma skin lesions in vivo.

Adult↗
PubMed1997

Role of estrogen deficiency in pathogenesis of secondary hyperparathyroidism and increased bone resorption in elderly women.

Whether the increased bone resorption and secondary hyperparathyroidism in elderly women is due to aging or to estrogen deficiency is unclear. To address this issue, we measured serum intact parathyroid hormone (PTH) and biochemical markers in serum and urine samples from 30 premenopausal women (32 +/- 0.5 years, mean age +/- SE), 30 estrogen-deficient postmenopausal women (74.2 +/- 0.6 years), and 30 elderly women (73.8 +/- 0.6 years) receiving long-term estrogen treatment. Because of the first and third groups were comparable in estrogen status but not in age, whereas the second and third groups were comparable in age but not in estrogen status, the independent effects of age and estrogen deficiency could be assessed quantitatively. Mean values were higher in the estrogen-deficient postmenopausal women than in the premenopausal women for serum PTH (by 33%, p < .01) and for bone resorption markers [by 50% p < .001) for urine cross-linked N-teleopeptide of type I collagen (NTx); 34% (p < .001) for urine pyridinoline (Pyd); and 36% (p < .001) for urine deoxypyridinoline (Dpd)]. However, mean values for serum PTH in the postmenopausal women receiving estrogen treatment did not differ from those in the premenopausal women, and mean values for bone resorption markers were not different (urine NTx and Pyd) or were lower [urine Dpd, by -12%, (p < .005)]. These findings suggest that late consequences of estrogen deficiency rather than age-related processes per se are the principal causes of the secondary hyperparathyroidism and increased bone resorption in elderly women.

Adult↗
PubMed1997

Assays of type I procollagen domains and collagen fragments: problems to be solved and future trends.

The biochemical possibilities for developing specific assays for type I collagen metabolism are described. Type I collagen synthesis can be assessed either by the analysis of the carboxyterminal or aminoterminal propeptides, which are in principle produced in a molar ratio of 1:1. However, in clinical situations altered behaviour can be found, the reasons for which may be altered clearance or even the existence of variant forms of type I collagen. Type I collagen degradation can be specifically detected by analysis of either cross-linked carboxy- or aminoterminal telopeptides or by the cross-links themselves liberated during the degradation processes. The heterogeneity of the cross-links and the constituent chains of the cross-linked peptides in different tissues and possibly in different clinical situations introduce problems, which should be studied and resolved in the future.

Biomarkers↗
PubMed1997

Effect of topical tretinoin on non-sun-exposed human skin connective tissue: induction of tenascin but no major effect on collagen metabolism.

The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cream on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatments, suction blisters were induced and amino-terminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) (experiments 1 and 3) and carboxy-terminal propeptide of type I procollagen (PICP) (experiment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) were assayed by the zymography method in experiment 2. In experiment 3, histology, immunohistochemistry of type I and III procollagens, tenascin, mRNA levels of type I collagen alpha 1-chain [alpha 1 (I)], interstitial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the levels of alpha 1 (I) collagen mRNA by a quantitative polymerase chain reaction method were studied. The proportional area of elastic fibres visualized in Verhoeff-stained sections was analysed by computerized digital image analysis. The results indicated that treatment with topical tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical staining, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone-17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was found after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the inhibitory effect of a potent corticoid on collagen propeptides.

Abdomen↗
PubMed1996

Monitoring the action of clodronate with type I collagen metabolites in multiple myeloma.

In our previous double-blind trial, we reported that clodronate reduced the incidence of bone lesions, fractures, pain and hypercalcaemia in multiple myeloma. Recently, it has been assumed that the antiresorptive effect of bisphosphonates on the osteoclasts is mediated through the osteoblasts. We therefore determined, in 244 patients of the same trial, serum assays of aminoterminal propeptide of type I procollagen (PINP) and type I collagen degradation product (ICTP). PINP is an early synthesis product of proliferating osteoblasts, in comparison to the alkaline phosphatase (AP) which is secreted by differentiated osteoblasts during the maturation phase of collagen. ICTP circulates in serum when old bone is resorbed. Our results indicate that after 25 months, the PINP levels decreased in the clodronate group (from 68.9 +/- 4.4 micrograms/l to 37.2 +/- 3.5 micrograms/l; P < 0.001) but not in the control group (from 61.5 +/- 3.2 micrograms/l to 69.3 +/- 7.5 micrograms/l; P < NS). The fall in the ICTP levels was markedly steeper in the patients receiving clodronate (from 8.38 +/- 0.80 micrograms/l to 4.58 +/- 0.32 micrograms/l; P < 0.01) than placebo (from 7.84 +/- 0.53 micrograms/l to 6.45 +/- 0.95 micrograms/l; P = NS). A significant difference between the study groups was seen at 4 months in the PINP, at 7 months in the ICTP and at 13 months in the AP levels, suggesting that clodronate affected through the proliferating osteoblasts, the osteoclasts, and through the osteoclasts, the differentiated osteoblasts. High baseline ICTP, PINP and AP levels indicated a poor prognosis. The decrease of the markers by clodronate was more marked in survivors than in non-survivors.

Aged↗