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Biomedical subjects

L Risteli

Publications and source records attributed to L Risteli.

At least 55 records · Page 3Linked to original sources
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↗
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↗
PubMed1996

Changes in interstitial collagen metabolism during acute myocardial infarction treated with streptokinase or tissue plasminogen activator.

Collagen plays a specific role in the maintenance of vascular integrity and in the thrombosis and scar formation processes. Therefore we found it interesting to study the changes in interstitial collagen metabolism during acute myocardial infarction treated with thrombolytic agents. Changes in collagen synthesis were evaluated by obtaining assays of the serum concentrations of the carboxyterminal propeptide of type I procollagen. Except fibrin plasmin is capable of degrading extracellular matrix components including collagen, and this capability was evaluated by monitoring the serum concentrations of the aminoterminal propeptide of type III procollagen. Twenty-four patients with suspected acute myocardial infarction and indications for thrombolytic therapy were randomized to receive either streptokinase (n = 11) or tissue plasminogen activator (n = 13). The patient groups were identical in their clinical characteristics. Serum levels of the aminoterminal propeptide of type III collagen increased rapidly on infusion of the thrombolytic agents, with the maximal mean increases of 44% and 16% in the streptokinase and TPA-treated groups, respectively. Levels of the carboxyterminal propeptide of type I collagen did not change during the thrombolytic therapy. A transient decrease occurred in the type I propeptide concentration at postinfarction day 2, and this decrease was followed by a secondary increase at days 4 to 6 in both patient groups studied. We conclude that thrombolytic agents stimulate the breakdown of interstitial collagen and that the collagen-degrading activity of TPA is lower than that of streptokinase. This factor may contribute to the relatively higher rethrombosis rate seen after TPA, because exposed collagen in the affected vascular wall stimulates thrombosis formation. On the other hand, increased collagen degradation followed by inhibition of collagen synthesis in the infarcted myocardium might increase the risk for cardiac rupture, especially after streptokinase treatment.

Antithrombins↗
PubMed1996

Effect of inhaled beclomethasone on serum markers of collagen metabolism in postmenopausal asthmatic women.

The use of inhaled corticosteroids in bronchial asthma has widened, but there is a lack of data on their effect on bone collagen synthesis and degradation. This paper reports the effect of three dose levels (200, 1000 and 2000 micrograms day-1, 3 weeks each) of inhaled beclomethasone on specific characteristics of bone collagen metabolism in seven postmenopausal women with new asthma without any previous corticosteroid therapy. Serum aminoterminal (PINP) propeptide of human type I procollagen was seen, after an initial increase, to decrease significantly (from 42.2 to 35.5 micrograms l-1, P = 0.001) with the higher doses of inhaled beclomethasone, but no statistical change was found in the carboxyterminal propeptide (PICP) or type I collagen crosslinked telopeptide (ICTP). This data shows that type I collagen synthesis may be disturbed when using high-dose inhaled corticosteroids. However, further studies are needed to assess the effects of inhaled beclomethasone on the ability of the osteoblasts to form bone matrix, and on the density of bone during a longer treatment period with inhaled corticosteroids.

Administration, Inhalation↗
PubMed1996

Type I and type III collagen metabolites in adult osteosarcoma patients.

Three biochemical markers of collagen metabolism were measured in 39 osteosarcoma patients. The pretreatment values did not predict outcome, and the markers showed no consistent change upon development of metastases. Both the age of the patients and the multimodality therapy affected the collagen metabolites. These findings emphasise the need for cautious interpretation of tumour-associated markers.

Adolescent↗
PubMed1996

Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma.

Thirty-six patients with bone metastases included in a trial of supportive calcitonin on the treatment response to systemic therapy were monitored by conventional radiography, conventional indicators of bone metabolism [alkaline phosphatase (AP), osteocalcin (gla), urinary hydroxyproline excretion (OHP), urinary calcium (uCa), serum calcium (sCa)] and collagen metabolites (ICTP, the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen; PICP, the carboxy-terminal propeptide of type I procollagen; and PIIINP the amino-terminal propeptide of type III procollagen). All patients had been on the same systemic treatment for at least 3 months at the start of the trial. There was a positive correlation between the concentrations of ICTP and PICP at baseline (Spearman's rank-order correlation coefficient rs = 0.62). Both ICTP and PICP showed statistically significant correlations to the other markers of bone metabolism (except sCa and uCa) as well as to the number of bone metastases on bone scans. Reduction in ICTP correlated significantly with the treatment response at three months (rs = - 0.57). while PICP showed a borderline negative correlation to therapy response (rs = - 0.37). Of all the biochemical parameters studied the changes in ICTP showed the best correlation with the treatment response. PICP and ICTP changes in patients with progressive disease differed significantly from those in patients with responding and stable metastases, whereas no difference was found between responders and stable patients.

Antineoplastic Agents↗
PubMed1996

Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women.

The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L-1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.

Administration, Cutaneous↗
PubMed1996

Mechanism of collagen network stabilization in human irreversible granulomatous liver fibrosis.

BACKGROUND & AIMS: Cross-linking participates in the increased stability of collagen towards proteolytic degradation. Liver collagen cross-linking by pyridinoline, from the lysyl oxidase pathway, and by pentosidine, issued from glycation, was investigated to determine their respective contribution to collagen stabilization in patients with an irreversible liver fibrosis caused by the parasitic granulomatous disease alveolar echinococcosis. METHODS: Liver pyridinoline and pentosidine were analyzed by high-performance liquid chromatography, and urinary pyridinoline was analyzed by immunoassay. Cross-linked type I collagen was localized by immunohistochemistry with an antibody against the C-terminal part of the molecule, involved in pyridinoline formation, that was measured in serum by radioimmunoassay. RESULTS: In contrast to pyridinoline, pentosidine decreased in fibrotic lesions. Cross-linked I collagen was located predominantly in collagen bundles in the periparasitic granuloma. Serum pentosidine and urinary pyridinoline levels did not differ significantly from controls, but the serum concentration of the C-terminal telopeptide of type I collagen increased significantly. CONCLUSIONS: Lysyl oxidase-mediated cross-linking is the major process contributing to the stabilization of collagen in granulomatous fibrosis, and glycation is not significantly involved in it. The changes induced by alveolar echinococcosis in liver collagen metabolism are associated with an increase in serum C-telopeptide of type I collagen.

Amino Acids↗
PubMed1996

Changes in bone markers in children with asthma during inhaled budesonide and nedocromil treatments.

We evaluated serum and urinary markers of bone turnover in 14 children with asthma during inhaled budesonide and nedocromil treatments. Both the markers of formation (serum carboxy- and amino-terminal propeptides of type I procollagen and serum osteocalcin) and the markers of degradation (serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links) decreased (p < 0.05) during budesonide treatment for 6 months. During inhaled nedocromil treatment (for the following 6 months), the markers returned to the normal levels. These transient decreases in the markers of both formation and degradation of bone suggest that inhaled budesonide may slightly decrease the bone turnover rate. However, normal "coupling" between formation and degradation seemed to operate, e.g. a change in one resulted in a corresponding change in the other, so that net bone loss did not necessarily occur.

Anti-Asthmatic Agents↗
PubMed1996

Collagen synthesis activity in the aqueous humour of eyes with glaucoma surgery: a pilot study.

AIMS: The purpose of this pilot study was to test whether the rate of collagen synthesis is measurable in the aqueous humour samples in reoperated and previously unoperated eyes. METHODS: The material consisted of 28 eyes of 27 patients, aged 5 to 82 years, in whom aqueous humour samples were obtained during eye surgery. Fifteen patients had no history of previous eye surgery (control group) while 12 patients were re-operated (study group). The carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured by specific immunoassays in the aqueous humour samples. RESULTS: The mean concentration of PIIINP in the study group (8.4 (SD 12.5) micrograms/l) was statistically significantly larger than that of the control group (0.4 (0.4) micrograms/l) (p < 0.0037). The respective values for PICP were 98.8 (SD 177.7) micrograms/l in the study group and 0.7 (SD 2.8) micrograms/l in the control group (p < 0.0005). The eyes in the study group which were re-operated within 1 year showed values increased 20-fold compared with the eyes in the control group and those eyes in the study group which had had their previous operation more than a year ago. In three eyes aqueous humour samples were also obtained from the encapsulated Molteno bleb and showed values increased 12-fold compared with those from the anterior chamber. CONCLUSIONS: PICP and PIIINP immunoassays are suitable for measuring the rate of collagen synthesis in the aqueous humour and may be useful in studies on pharmacological modulation of wound healing in glaucoma surgery.

Adolescent↗
PubMed1996

Increased degradation of type I collagen in patients with inflammatory bowel disease.

To assess the mechanisms of osteopenia in inflammatory bowel disease (IBD), the serum markers of bone formation (osteocalcin and carboxyterminal propeptide of type I procollagen (PICP)) and bone degradation (carboxyterminal telopeptide of type I collagen (ICTP)), the bone mineral density (BMD) of the lumbar spine and the proximal femur and calcium intake of 150 unselected IBD patients and 73 healthy controls were investigated. The patients had higher ICTP values (3.69 (SD 1.40) microgram/l) than the healthy controls (3.25 (1.00) microgram/l, p = 0.035), but no differences in serum PICP and osteocalcin between these groups were detected. In the patients, the ICTP, PICP, and osteocalcin values did not have any significant correlation with BMD, but the patients with ICTP values above 3.6 microgram/l had significantly lower Z scores than those with lower ICTP. In the controls, however, a positive correlation between serum ICTP and BMD was found. The ulcerative colitis patients with total colitis had higher values of ICTP (3.96 (1.58) microgram/l) than those with a left sided disease (3.04 (0.86) micrograms/l, p = 0.009). The patients with a history of clinically active disease (n = 20) had higher ICTP (4.58 (1.55) microgram/l) and osteocalcin (12.56 (5.64) microgram/l) values than the patients (n = 130) with quiescent disease (ICTP 3.56 (1.33), p = 0.002, and osteocalcin 9.76 (3.62), p = 0.017). Increased serum osteocalcin, PICP, and ICTP concentrations and reduced BMD Z scores were found in a subgroup of Crohn's disease patients with a history of an active disease (n = 11). Raised serum ICTP and normal values of osteocalcin and PICP in IBD patients show increased breakdown of type I collagen without a compensatory increase in its synthesis suggesting an increased rate of bone degradation as a probable mechanism for osteopenia in IBD. Raised ICTP values are related to reduced bone mineral densities.

Adult↗
PubMed1996

Effects of an inhaled steroid (budesonide) on skin collagen synthesis of asthma patients in vivo.

Skin atrophy has been observed after prolonged use of inhaled corticosteroids. We therefore studied the effect of inhaled budesonide and nedocromil in patients with asthma on concentrations of procollagen propeptides in suction blister fluid reflecting skin collagen synthesis in vivo. Both types I and III procollagen propeptide concentrations decreased significantly after 6 wk of either 1,600 micro g/day (n=10) or 400 micro g/day (n=9) of inhaled budesonide but not in control subjects using inhaled nedocromil 16 mg/day (n=9). The reduction in mean propeptide concentrations ranged from 39 to 63%; the effects of the two budesonide doses did not differ significantly. Thus, even a low dose of inhaled corticosteroid represses skin collagen synthesis within a relatively short period.

Administration, Inhalation↗
PubMed1996

Expression of mRNAs for type I and type III procollagens in serous ovarian cystadenomas and cystadenocarcinomas.

Malignant ovarian tumors induce a strong fibro-proliferative reaction characterized by the active production of type I and type III procollagen both locally in the ovary as well as more remotely in the peritoneal cavity. Our purpose was to determine the origin of the increased collagen production observed in serous ovarian tumors with different histological grades of malignancy, ie, whether the malignant cells or the stromal fibroblasts are responsible for the synthesis of collagen fibers. We visualized the mRNAs corresponding to the pro alpha 1(I) and pro alpha 2(I) chains of type I procollagen and the pro alpha 1(III) chain of type III procollagen by in situ hybridization. Strong signals for both chains of type I procollagen were seen in stromal fibroblasts next to tumor cell islets, whereas the reaction was weak or absent near benign ovarian cysts. In poorly differentiated tumors, the signals were particularly abundant and occasionally also seen in the neoplastic cells themselves. Type III procollagen mRNA expression was similar, although somewhat less distinct. These findings indicate that the production of interstitial procollagens is related to the degree of malignancy and neoplastic activity of tumors. The formation of collagen in well differentiated ovarian tumors is a function of stromal fibroblasts, whereas in poorly differentiated tumors, aberrant expression of one or several chains of type I and type III procollagens in the neoplastic cells is also likely to take place.

Antisense Elements (Genetics)↗
PubMed1996

Immunoassay for intact amino-terminal propeptide of human type I procollagen.

We have developed quantitative immunoassays for the intact, trimeric amino-terminal propeptide of human type I procollagen (PINP) and its Col1 domain. Intact PINP was isolated from the pleural fluids of cancer patients by a combination of ion-exchange, gel-filtration, and reversed-phase chromatographies. The amino-terminal Col1 domain of PINP was isolated after bacterial collagenase treatment of the heat-denatured trimeric propeptide. For the intact PINP assay we used a polyclonal antibody with only 1.2% cross-reaction with the monomeric Col1 domain. In human serum, this assay detects only one peak of PINP antigenicity that has the size of known intact PINP. Under similar conditions, an assay for the Coll domain of PINP recognized two circulating antigens. The biological relevance was further verified in wound fluid. Interassay and intraassay CVs were 3.1-9.3% for values within the reference intervals (mean +/- 2SD) for intact PINP in serum, which were 19-84 microg/L for women and 20-76 microg/L for men.

Adult↗
PubMed1995

Immunohistochemical study of type I collagen and type I pN-collagen in benign and malignant ovarian neoplasms.

BACKGROUND: Type I collagen is a major constituent of the interstitial connective tissue. Although ovarian carcinoma is known to induce the expression of type I collagen in the peritoneal cavity, the distribution and metabolic activity of this collagen in ovarian tumor tissue are not known. METHODS: The distributions and staining intensities of different molecular forms of type I collagen in ovarian neoplasms were studied immunohistochemically with antibodies to the aminoterminal propeptide of type I procollagen (PINP) and the cross-linked carboxyterminal telopeptide of type I collagen (ICTP), reflecting the presence of newly synthesized and old, cross-linked type I collagen, respectively. RESULTS: A regular pattern of moderately staining, relatively uniform fibers was observed in the stroma of benign serous and mucinous cystadenomas, indicating limited participation in tumor growth. The staining was accentuated subepithelially in borderline epithelial neoplasms and in well differentiated cystadenocarcinomas, suggesting induction of the stromal collagen synthesis by the tumor cells. Fewer degraded collagen fibers were found in moderately differentiated carcinomas, most likely because of enzymatic degradation of the stroma surrounding the neoplasms during tumor spread. Strongly staining, irregular collagen fibers occurred closely around islets of tumor cells in undifferentiated malignant neoplasms and in metastases of ovarian carcinomas; also, intracellular staining was present in part of the malignant cells. In most cases, the staining reactions obtained with the two different antibodies were similar, probably indicating rapid processing of the newly synthesized type I collagen (indicated by PINP) to a maturely cross-linked form (indicated by ICTP). CONCLUSIONS: Synthetic and degradative processes are typical of the collagenous matrix in malignant ovarian tumors. Aberrant expression of type I collagen may occur in anaplastic ovarian carcinomas.

Adult↗
PubMed1995

Responses of type I and type III collagen synthesis after replacement of the hip joint.

Liberation of the carboxy-terminal propeptide of type I procollagen (PICP) and the amino-terminal propeptide of type III procollagen (PIIINP) into body fluids reflects synthesis of the respective collagen types. Here, we followed PICP and PIIINP in serum with specific radioimmunoassays after hip surgery. Preoperative median of S-PICP was 112 micrograms/liter (range 87 to 154, n = 9), the 1-day median being 58 micrograms/liter (33 to 79). The corresponding medians for S-PIIINP were 4.4 micrograms/liter (3.5 to 7.0) and 3.3 micrograms/liter (2.0 to 3.5). The medians reached their maximums 14 days after surgery, 172 micrograms/liter (122 to 440) for S-PICP and 12.4 micrograms/liter (8.0 to 15.4) for S-PIIINP, after which the preoperative values were slowly approached over several months. Comparable results were found in a greater sample (n = 50). Our results indicate that the synthesis of structural collagen is inhibited immediately after surgery, but the inhibition is soon overcome by active collagen synthesis at the site of trauma. Collagen metabolism remains activated for several months after surgery.

Collagen↗