Serum PICP Concentrations Research Articles

Fragmented QRS complexes are a marker of myocardial fibrosis in hypertensive heart disease.

Carboxy-terminal propeptide of type 1 procollagen (PICP) is a marker of extracellular collagen synthesis. Fragmented QRS (fQRS) on a 12-lead electrocardiogram (ECG) has been demonstrated as a marker of myocardial fibrosis. The present objective was to investigate the association between serum PICP concentration and presence of fQRS on ECG in hypertensive patients. Consecutive patients with previously or newly diagnosed hypertension were included. fQRS was defined as the presence of additional R-wave (R'), or notching of R- or S-waves, or the presence of fragmentation in 2 contiguous ECG leads. Serum PICP levels were measured by ELISA method. The study group consisted of 90 hypertensive patients (74% females, with a mean age of 54.7±8.5 years). Of these patients, 47 (52.2%) had fQRS on ECG. Age (p=0.121) and gender distribution (p=0.625) were similar in patients with or without fQRS. Receiver operating characteristic curve analysis yielded a strong predictive ability of PICP levels for the presence of fQRS (area under the curve: 0.850; 95% CI: 0.772-0.929; p<0.0001). In multivariate logistic regression analysis, PICP levels were strongly and independently associated with the presence of fQRS (OR: 1.938; 95% CI: 1.398-2.688). Serum PICP level is a strong and independent predictor of fQRS. Discriminative performance of serum PICP levels for the presence of fQRS is high. The present results are the first to demonstrate that fQRS may indicate myocardial fibrosis in patients with hypertension.

Relationship between stages of the estrous cycle and bone cell activity in Thoroughbreds

To investigate the relationship between stage of estrous cycle and bone cell activity in Thoroughbreds. Blood samples collected from forty-seven 2-year-old Thoroughbred mares in training for racing. Blood samples were collected monthly (in April through September) from the mares. Stage of estrus was determined by assessing serum progesterone concentration. Bone cell activity was determined by measuring concentrations of 2 markers of bone formation (osteocalcin and the carboxy-terminal propeptide of type I collagen [PICP]) and a marker of bone resorption (the cross-linked carboxy-terminal telopeptide of type I collagen [ICTP]) in sera. When the relationship between stage of the estrous cycle and markers of bone cell activity was examined, serum concentrations of both osteocalcin and ICTP were significantly higher in mares that were in the luteal phase, compared with mares that were at other stages of the estrous cycle. Stage of estrus did not affect serum PICP concentration. Results indicate that bone cell activity in Thoroughbred mares fluctuates during the estrous cycle; serum concentrations of markers of bone formation and bone resorption are increased during the luteal phase. Further studies are required to determine whether these changes are of clinical importance and increase the risk of injury for mares in training during the breeding season. As in humans, stage of estrus must be considered as a source of uncontrollable variability in serum bone marker concentrations in horses.

The relation between myocardial cyclic variation of integrated backscatter and serum concentrations of procollagen propeptides in hypertensive patients

Cyclic variation of integrated backscatter (IBS), or CVIBS, provides a noninvasive method to measure myocardial collagen deposition and ischemia in hypertensive patients. We hypothesized that serum procollagen propeptides can offer additional values to CVIBS for evaluating cardiac changes related to fibrosis or ischemia. A total of 21 patients were enrolled in this study and were divided into three groups according to the presence of hypertension and serum carboxyterminal propeptide of type I procollagen (PICP) concentration; these were: 7 hypertensive patients with PICP ≥ 127 μg/L (group 1), 7 hypertensive patients with PICP < 127 μg/L (group 2), 7 normotensive subjects with PICP < 127 μg/L (group 3). In addition to PICP, serum aminoterminal propeptide of type III procollagen (PIIINP), stress 201thalium scintigraphy and CVIBS were examined. Phase-compensated amplitudes of CVIBS at mid posterior and mid anteroseptal segments were significantly lower in group 1 ( p < 0.05). Patients with fixed 201thallium perfusion defects had lower phase-compensated amplitudes of CVIBS at mid anteroseptal segment and higher PIIINP concentrations ( p < 0.05). In conclusions, decrease of myocardial phase-compensated amplitude accompanied with increase of serum PICP concentration may be indicative of the underlying fibrotic process of hypertensive myocardium. Decrease of this CVIBS parameter with increase of serum PIIINP implies concomitant myocardial ischemia. (E-mail: lun0630@ha.mc.ntu.edu.tw)

Discrepant expression of carboxy- and aminoterminal propeptides of type I procollagen predicts poor clinical outcome in epithelial ovarian cancer

Objective The metabolism and prognostic value of serum concentrations of the aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen and the PICP:PINP ratio in relation to the carboxyterminal telopeptide of type I collagen (ICTP) in ovarian cancer were evaluated. Methods Fifty patients with epithelial ovarian cancer were evaluated with serial measurements of serum concentrations of PICP, PINP, and ICTP before the operation and at 3-month intervals during the first year after the operation. For statistical analysis the patients were divided into two groups according to clinical outcome (alive vs dead) and clinical behavior (fast progression vs others). Results The serum PINP concentration before the operation was increased and the PICP/PINP ratio was lowered in patients with poor prognosis (PP) compared to those with good prognosis (GP) and in patients with fast progression compared to others. The serum PICP concentration did not differ between the groups. The circulating ICTP concentration was significantly higher in the PP-group than in the GP group. In Kaplan–Meier analysis the PICP:PINP ratio divided the PP and GP patients ( P = 0.0004). In multivariate regression analysis, the independent prognostic variables were clinical stage ( P = 0.014, 95% confidence interval (CI) 1.31–11.19) and preoperative serum ICTP concentration ( P = 0.048, CI 1.01–5.91). When serum ICTP concentration was excluded from the equation, the PICP:PINP ratio ( P = 0.012, CI 1.29–7.83), together with clinical stage ( P = 0.013, CI 1.31–10.37), was found to be an independent prognostic variable. When the early and advanced stage patients were analyzed separately, the PICP:PINP ratio was a significant prognostic variable in multivariate analysis in early stage patients and in advanced stages during the first 4 years of follow-up. Conclusion A low PICP:PINP ratio was associated with fast progression and poor clinical outcome in ovarian cancer. Evaluation of the PICP:PINP ratio together with ICTP may be valuable in predicting the clinical outcome of ovarian cancer.

Effects of IGF-I combined with GH on glucocorticoid-induced changes of bone and connective tissue turnover in man.

Chronic glucocorticoid therapy results in negative bone and connective tissue balance. To assess the effects of GH and a combination of IGF-I and GH, 24 healthy male volunteers received in a double blind fashion either recombinant human GH (0.3 IU/kg per day s.c.), or a combination of GH (0.3 IU/kg per day s.c.) and IGF-I (80 microgram/kg per day s.c.) or placebo (saline s.c.) during 6 days of methylprednisolone (0.5 mg/kg per day) treatment. Methylprednisolone decreased serum osteocalcin concentrations during placebo treatment from 32.9+/-2.1 to 9.0+/-1.4 microgram/l (P<0.0001), indicating diminished osteoblast activity, and procollagen type I (PICP) and procollagen type III (PIIINP) to 46 and 70% of baseline respectively (P<0.005), indicating diminished bone (PICP) and soft tissue collagen synthesis (PIIINP). Urinary excretion of pyridinoline, deoxypyridinoline and hydroxyproline increased during treatment with methylprednisolone alone, indicating increased bone resorption (P<0.05 or less). The combination of GH and IGF-I resulted in a significant blunting of the methylprednisolone effect on serum PICP and PIIINP concentrations (P<0.005 or less vs placebo); this effect was in part due to IGF-I, since serum PICP concentrations decreased less in the combination group than during GH treatment alone (P<0.05). In the groups receiving GH and GH combined with IGF-I, urinary hydroxyproline excretion increased more when compared with methylprednisolone alone (P<0.05 or less). These findings demonstrate that only the combination of GH and IGF-I, but not GH alone, markedly counteracts diminished bone and body collagen synthesis caused by glucocorticoids, whereas connective tissue resorption is enhanced during treatment with GH alone and in combination with IGF-I.

Time-dependent changes of serum carboxy-terminal peptide of type I procollagen and carboxy-terminal telopeptide of type I collagen concentrations in patients with acute myocardial infarction after successful reperfusion: correlation with left ventricular volume indices

To test the hypothesis that in patients with acute myocardial infarction (AMI), changes in the concentrations of the serum carboxy-terminal peptide of type I procollagen (PICP) and the carboxy-terminal telopeptide of type I collagen (ICTP) reflect extracellular matrix reformation and degradation, respectively, in the infarct healing processes, we measured these serum concentrations by RIA and compared their values with left ventricular (LV) indices obtained by left ventriculography. We studied 13 consecutive patients with their first AMI who underwent successful reperfusion. Blood samples were taken the day of admission and on days 2, 3, 4, 5, 7, and 14. LV volume indices were determined at 1 month after AMI, when LV remodeling was almost completed. The serum concentrations of both PICP and ICTP changed in a time-dependent manner. The average serum PICP concentration was lower than 1 SD below the mean control values on days 2 and 3 and increased thereafter, returning to the lower end of the control range at day 14. The area under the curve (AUC) for PICP was significantly correlated with the LV end systolic (ES) and end diastolic (ED) volume indices and LV ejection fraction for the first 14 days after AMI. The serum PICP on days 5-14 was inversely correlated or tended to be correlated with the LVES and LVED volume indices. The average serum ICTP concentrations on admission were within the control range, began to increase on day 2, and reached maximal concentrations on day 5, remaining at a plateau concentration until day 14. Although the AUC of ICTP for 14 days, the ICTP concentrations on days 1 and 14, and the minimal and maximal concentrations were significantly correlated with creatine kinase (CK) release and the period from AMI onset to the peak CK time, the concentrations were not significantly correlated with any LV indices except for the concentration on day 4, which was weakly correlated with the LVES volume index. The serum concentrations of PICP showed a significant time-dependent change that correlated with LV indices, indicating that PICP may provide additional information for evaluating the healing process because it affects LV remodeling after AMI. Although the serum concentration of ICTP changed in association with CK release, the ICTP concentration was found to be a poor indicator for LV indices.

Carboxy-terminal propeptide of human type I collagen and pyridinium cross-links as markers of bone growth in infants 1 to 18 months of age

Serum carboxy-terminal propeptide of human type I collagen (PICP) concentrations, as a marker for bone formation, and urinary pyridinium (Pyd) cross-link concentrations, as a marker of bone resorption, were determined in 66 healthy infants aged 1-18 months who are being studied longitudinally. We hypothesized that there would be a positive correlation of growth velocity, increase in bone area, and bone mass accretion rates with PICP and Pyd cross-link concentrations. Since osteocalcin is currently used as a marker of bone formation, serum osteocalcin concentrations were also measured. Mean serum PICP and urinary Pyd cross-link concentrations were significantly greater than adult concentrations. Future growth velocity, increase in bone area, and bone mass accretion rates were not associated with PICP, Pyd cross-link, or osteocalcin concentrations. Growth velocity during the 3 months preceding sample collection correlated with serum PICP, Pyd/kg, and osteocalcin concentrations (r = 0.474, p < 0.001; r = 0.379, p < 0.001; and r = 0.516, p < 0.001, respectively). Previous increase in bone area correlated with serum PICP concentrations (r = 0.359, p = 0.01). The relationship between the infant's previous bone mass accretion rate and PICP was of borderline significance (r = 0.281, p = 0.055). In summary, normative data for PICP, Pyd cross-link concentrations, and parameters of bone growth are provided for infants 1-18 months of age and indicate that these markers reflect past and current bone metabolism and may be helpful in monitoring bone disorders in infants.

Serum Levels of the Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen and Laminin Are Elevated in Graves' Disease but Not in Toxic Nodular Goiter

We determined serum levels of laminin, carboxyterminal cross-linked telopeptide, and carboxyterminal propeptide of type I collagen (ICTP and PICP) in 27 patients with Graves' disease (GD) and in 31 patients with toxic nodular goiter (TNG). Elevated levels of soluble laminin and ICTP were observed in patients with GD prior to treatment (mean ± SD concentration 1444 ± 404 and 8.6 ± 3.5 ng/ml, respectively), compared to patients with TNG (476 ± 103 and 4.2 ± 1.5 ng/ml) and normal controls (492 ± 112 and 3.1 ± 1.3 ng/ml, n = 34). In contrast, serum PICP concentrations were not different between patients with GD or TNG and normal controls. In GD patients serum ICTP and laminin levels decreased during thiamazole treatment and normalized within 4 and 8 weeks of therapy. There was no correlation between serum ICTP and laminin levels and serum levels of thyroid hormones and/or autoantibodies, respectively. Serum ICTP and laminin could be markers for alterations of extracellular matrix during GD and release of matrix components in the circulation and/or reflect an impaired clearance.

Effects of infusion of parathyroid hormone and primary hyperparathyroidism on formation and breakdown of type I collagen

The influence of chronic and acute exposure to parathyroid hormone (PTH) on formation and breakdown of type I collagen, using two recently developed radioimmunoassays for serum PICP (the carboxyterminal propeptide of type I procollagen) and serum ICTP (the carboxyterminal telopeptide of type I collagen), have been evaluated. Fasting morning values were obtained from 18 women with primary hyperparathyroidism (HPT) and an equal number of age-matched, healthy controls. A 24-hour infusion of synthetic human parathyroid hormone (PTH 1-38) was performed in 14 healthy females. The patients with HPT had higher values for serum ICTP than the controls (6.0 +/- 3.0 and 4.1 +/- 2.1 micrograms/liter; P < 0.05), whereas the serum PICP concentrations were not different (170 +/- 72 and 151 +/- 65 micrograms/liter; n.s.). During infusion of PTH in healthy subjects, there was an increase of the serum ICTP concentrations (from 3.6 +/- 1.3 to 4.4 +/- 1.8 micrograms/liter; P < 0.001) whereas those of serum PICP decreased (from 185 +/- 78 to 118 +/- 42 micrograms/liter; P < or = 0.0001). The increase of serum ICTP during infusion of PTH was positively related to the increase of serum calcium and other indices of bone resorption, i.e., fasting urinary excretions of hydroxyproline and calcium. The decrease of serum PICP was also related to the changes of serum ICTP and hydroxyproline in urine, serum calcium, and alkaline phosphatase but not to osteocalcin, an established marker of osteoblastic activity. The findings support the fact that serum ICTP is a valuable method for evaluating bone resorption and is also easy to perform.(ABSTRACT TRUNCATED AT 250 WORDS)

TYPE-I AND TYPE-III PROCOLLAGEN METABOLITES AND CA 125 IN EPITHELIAL OVARIAN-CANCER

The clinical courses of 24 patients with advanced epithelial ovarian cancer were monitored with serial serum CA125, PIIINP and PICP determinations before, during and after treatment. Initial serum CA125, PIIINP and PICP concentrations were pathologic in 93%, 80% and 11% of the cases, respectively. Eight patients responded to therapy with complete remission and 16 patients died of the malignancy. Initial serum PIIINP concentration, but not that of CA125 or PICP, was significantly lower in responders than in nonresponders. The pathologic serum CA125 and PIIINP levels of the responders decreased to normal within two months, whereas in patients with a poor prognosis they remained elevated. Serum CA 125 and PIIINP responded to progression with an increase and to remission with a decrease. The changes in the serum PICP concentration took place predominantly within the reference interval. In seven patients with progressive malignancy, it increased to a pathologic level during the final stage of the disease. Our results indicate that extensive ovarian malignancy strongly affects the metabolism of type I and type III collagens. The PIIINP assay is clinically useful. PIIINP and PICP determinations also have potential to increase our understanding of the mechanisms of invasion and spread of malignant tumours.