Procollagen III Aminoterminal Propeptide Research Articles

Inflammation and Fibrosis in Sleep-Disordered Breathing after Acute Myocardial Infarction.

After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurrence of heart failure after AMI. We hypothesize that sleep-disordered breathing (SDB) promotes inflammation and myocardial fibrosis, leading to reduced myocardial salvage. Therefore, in patients with first-time AMI successfully treated with percutaneous coronary intervention (PCI), we aimed to investigate whether circulating levels of high-sensitivity C-reactive protein (hs-CRP) and PIIINP are elevated in patients with SDB compared to patients without SDB. This cross-sectional analysis included a total of 88 eligible patients with first AMI and PCI pooled from two prospective studies and stratified according to the apnea-hypopnea index (AHI, with SDB: AHI ≥ 15 h-1). We analyzed circulating levels of hs-CRP and PIIINP 3-5 days after PCI. Patients with SDB had significantly higher levels of hs-CRP (18.3 mg/L [95% CI, 8.0-42.6] vs. 5.8 mg/L [95% CI, 4.2-19.8], p = 0.002) and PIIINP (0.49 U/mL [95% CI, 0.40-0.60] vs. 0.33 U/mL [95% CI, 0.28-0.43], p < 0.001). In a multivariable linear regression model accounting for important clinical confounders, SDB significantly predicted circulating levels of hs-CRP (p = 0.028). Similarly, only SDB was independently associated with PIIINP (p < 0.001). Only obstructive but not central AHI correlated with circulating levels of hs-CRP (p = 0.012) and PIIINP (p = 0.006) levels. The presence of obstructive SDB after AMI was independently associated with increased circulating levels of hs-CRP and PIIINP. Our results emphasize the important role of SDB as a common comorbidity and indicate increased inflammation and myocardial fibrosis in these patients.

A Phase 1 study for safety and pharmacokinetics of BIO101 (20-hydroxyecdysone) in healthy young and older adults.

Sarcopenia is an age-related skeletal muscle disorder characterized by loss of muscle mass and strength leading to mobility disability. 20-Hydroxyecdysone (20E) is a polyhydroxylated plant steroid that demonstrates pharmacological effects in many disease animal models including ageing/sarcopenia. BIO101 is a 20E purified investigational drug (≥97%) that previously demonstrated good toxicology profiles in rat and dog. BIO101 is evaluated in healthy young and older adults in a Phase 1 study. This study is a Single Ascending Dose (SAD) followed by a 14-day Multiple Ascending Dose (MAD). In SAD, BIO101 was administered orally to 16 young adults at doses from 100 to 1400mg and to 8 older adults (age ≥65years) at 1400mg. In MAD, doses of 350mg once daily (qd), 350mg twice daily (bid) and 450mg bid were administered to 10 older adults. The primary objective was to evaluate safety and pharmacokinetics (PK), including dosing of circulating metabolites. Pharmacodynamic effects were investigated with regard to myostatin, procollagen-III-amino-terminal propeptide (PIIINP), myoglobin, creatine-kinase Muscle Brain (CKMB), renin and aldosterone plasma/serum levels. BIO101 showed a good safety profile with only mild to moderate adverse events and a satisfactory pharmacokinetic profile. In SAD, at 100mg to 1400mg, mean Cmax and areas under the curve increased less than dose-proportionally. Mean half-life was short (2.4-4.9h), and mean renal clearance was comparable in all doses (4.05-5.05L/h). Mean plasma exposure was slightly lower in older adults (22% lower for Cmax and 13%-15% lower for AUCs) compared with young subjects. In MAD, 350 and 450mg bid led to a slight accumulation over 14days (mean ratio of accumulation [Rac] of 1.31 in both cohorts). Reduction of biomarkers (myoglobin, CK-MB) mean serum levels (vs. baseline) was observed at 450mg bid. Two major metabolites of 20E (14-deoxy-20-hydroxyecdysone and 14-deoxypoststerone) were identified and quantified. BIO101 shows a good safety and pharmacokinetic profile that led to the selection of doses for the subsequent interventional clinical trials of Phase 2 in age-related sarcopenia (SARA-INT) and Phase 3 in Covid-19 (COVA).

Analysis of current status of quantitative detection of biomarkers for liver fibrosis in Clinical labs in China.

AimTo explore the quality control and implementation of the quantitative detection of liver fibrosis biomarkers, laminin (LN), collagen IV (Col Ⅳ), procollagen III amino‐terminal propeptide (PⅢNP), hyaluronic acid (HA), and cholyglycine (CG), in China.MethodsTwo quality control products were measured in different laboratories using different measurement methods and reagents, and the acquired results were subjected to analysis. The quantitative detection technique was based on the conventional assessment criteria, with a target value ±30% being employed.ResultsHundred labs were involved in the External Quality Assessment with 88 laboratories completing the assessment, and the pass rates were 84%, 80.2%, 67.5%, 77.3%, and 58.3% for HA, LN, PⅢNP, Col Ⅳ, and CG, respectively. Chemiluminescence immunoassay was used most for HA (90.1%), LN (90.1%), PⅢNP (87.9%), and Col Ⅳ (82.9%) determination, whereas the chemiluminescence immunoassay (31.6%), latex‐enhanced immunoturbidimetry (36.7%), and homogeneous enzyme immunoassay (26.7%) were used for CG determination. The coefficients of variation for HA, LN, PⅢNP, Col Ⅳ, and CG in different laboratories were 3.3%–19.49%, 1.74%–38.81%, 1.97%–41.29%, 2.85%–41.69%, and 2.71%–41.8%, respectively.ConclusionThe clinical quantitative detection of liver fibrosis biomarkers is highly performed in China. The existing problems are that there are many manufacturers producing reagents and instruments, the quality of reagents is uneven, the specificity and sensitivity of reagents are greatly different, the comparability of results of various systems is poor, and the accuracy and consistency between different systems are lacking. All above underscores the critical importance of EQA in improving and monitoring the identification of biomarkers for liver fibrosis.

Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis-A Pilot Study.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Urinary procollagen III aminoterminal propeptide/creatinine (PIIINP/Cr) ratio and transforming growth factor beta/creatinine (TGF-β/Cr) ratio in children with idiopathic nephrotic syndrome on corticosteroid and cyclosporine A treatment

Idiopathic nephrotic syndrome is a common nephropathy in children basically treated with corticosteroids and, in some cases, with cyclosporin A. There are concerns that proteinuria itself and cyclosporin A could cause renal fibrosis via activation of transforming growth factor beta (TGF-β), which may stimulate deposition of collagen type III, synthesised as procollagen III amino terminal propeptide (PIIINP). The aim of this study was to assess urinary TGF-β and PIIINP to creatinine (Cr) ratio as markers of renal fibrosis in children with idiopathic nephrotic syndrome put on corticosteroid and cyclosporin A treatment. Materials and methods: The study comprised 20 children with idiopathic nephrotic syndrome in remission on prednisone, aged 6.87 years [interquartile range (IQR): 6.37]; 21 children with idiopathic nephrotic syndrome in remission on cyclosporin A, aged 9.66 years (IQR: 5.0); and 21 healthy subjects, aged 7.16 years (IQR: 9.0). First morning urinary PIIINP/Cr and TGF-β/Cr were obtained and compared with Mann–Whitney U test, with the level of significance at p ≤ 0.05. Results: PIIINP/Cr ratio was significantly elevated in the cyclosporin A group [3.44 (2.5) vs. 1.12 (0.96) μg/mmol], p = 0.000, as well as in the prednisone group when compared to controls [1.33 (1.58) vs. 1.12 (0.96) μg/mmol], p = 0.042. The TGF-β/Cr ratio was significantly higher only in the cyclosporin A group when compared to controls [4.03 (3.25) vs. 2.33 (1.62) μg/mmol], p = 0.004. Conclusions: Increased urinary PIIINP/Cr ratio in children with idiopathic nephrotic syndrome either on steroid or on cyclosporin A therapy may suggest that renal fibrosis is a process generally involved in idiopathic nephrotic syndrome. Elevated urinary TGF-β/Cr and PIIINP/Cr ratios in patients with idiopathic nephrotic syndrome on cyclosporin A may reflect nephrotoxicity of this drug.

Combined administration of microdoses of growth hormone and erythropoietin: Effects on performance and evaluation of GH detection capability using anti-doping methods.

The combination of growth hormone (GH) and recombinant erythropoietin (rEPO) is thought to be used particularly in endurance sports. Our objective was to reproduce a 2-week administration of rEPO microdoses alone or in combination with GH microdoses (three times a week) on healthy and athletic male subjects and to evaluate if GH had any additional effects compared to EPO treatment alone. The effects of the treatments on hematological parameters and VO2max were studied as well as the detection of GH in serum. While the rEPO microdose regimen was associated with a significant increase in reticulocytes, no clear elevation in hemoglobin concentration (HGB) was observed. Using a correction by plasma volume did not reveal more effects of EPO on HGB. Our results did not show any additional effect when the GH microdoses were co-administered. In addition, no clear increase in VO2max was observed after treatment, with an elevation in only half the subjects in both groups (EPO and EPO+GH). A clear effect of GH on insulin-like growth factor I (IGF-I) was seen but it was lower on procollagen III amino-terminal propeptide (P-III-NP). GH detection using the direct isoform test identified only one subject 24 hours after receiving GH. The GH biomarker test combining IGF-I and P-III-NP was not able to detect the GH administration. However, a longitudinal follow-up of the intraindividual variations showed a significant increase in IGF-I 24 and 48 hours after GH administration in most subjects, while the effect of GH microdoses on P-III-NP was less straightforward.

Urinary procollagen III aminoterminal propeptide and β-catenin – New diagnostic biomarkers in solitary functioning kidney?

Purpose: We aimed at evaluating urinary levels of procollagen III aminoterminal propeptide (PIIINP) and β-catenin and the relationship between these markers and clinical and laboratory variables in children with a solitary functioning kidney (SFK).Patients and methods: The study group consisted of 98 (M/F: 62/36) children with an SFK with a median age of 8 years. An age-matched control group contained 54 healthy peers. Urinary levels of procollagen III aminoterminal propeptide and β-catenin were measured using a commercially available immunoassay kit.Results: The urinary values of PIIINP (UPIIINP) were significantly increased in patients with SFK versus controls (p < 0.01). Our analysis revealed no significant differences in urinary β-catenin levels between the SFK patients and control subjects (p > 0.05). Only urinary PIIINP levels were correlated to renal function tests, such as serum creatinine, urea, uric acid, and estimated glomerular filtration rate (p<0.05).Conclusions: An increased urinary level of PIIINP may indicate early kidney impairment in children with SFK. Urinary β-catenin does not seem to play any important role as a marker of renal function in children with SFK. Further long-term studies are required in order to evaluate the clinical usefulness of these markers and their predictive value of chronic kidney disease (CKD) progression.

Peptide selection for the quantification of P-III-NP in human serum by mass spectrometry.

Procollagen III amino-terminal propeptide (P-III-NP) is currently monitored in human doping control as a biomarker for growth hormone administration and also in clinical diagnostics using immunoassays. Drawbacks to this approach have been highlighted and research is ongoing to develop a mass spectrometric method to complement these methods. However, a lack of traceable reference material, the presence of post-translational modifications (PTMs), and small blood concentration complicate the development of targeted analytical methods for P-III-NP quantification. Tryptic digest products of P-III-NP were assessed by liquid chromatography/mass spectrometry (LC/MS). In silico digestion was used to predict P-III-NP peptides for MS analysis; however, these excluded PTMs. With a priori knowledge of PTMs, we associated experimental P-III-NP peptides with those derived by in silico digestion. Synthesized P-III-NP peptides, hT1 (human) and T5 (human/bovine), were used to develop sensitive micro- and nano-flow LC/MS methods to analyse P-III-NP originating from human serum semi-quantitatively. P-III-NP peptides, T1 and T5, were identified using high-resolution accurate MS (HRAMS). PTMs modified the mass of observed peptides. N-terminal pyroglutamation (pE) in T1 and several hydroxylated prolines (hP) in T5 (G-X-hP motif) were observed. With PTM, hT1 and T5 were observed in a digest of immuno-captured P-III-NP by LC/MS. Using a semi-quantitative approach, hP-III-NP at basal concentrations of 2ng/mL (50pmol) could be estimated from a 200-μL sample volume. Consideration of PTMs is needed to identify P-III-NP peptides produced by digestion with trypsin. The information presented here now gives the most appropriate peptide sequences for synthesizing suitable reference materials required for quantification of human P-III-NP in blood and evidences methodology that is sufficiently sensitive to develop a quantitative method.

Extracorporeal Shockwave Lithotripsy Could Lead to a Prolonged Increase in the Renal Fibrotic Process of Up to 2 Years.

This prospective study aimed to evaluate the effect of ramping and pause protocols on renal fibrosis, blood pressure control, and renal function in patients receiving extracorporeal shockwave lithotripsy (SWL). This study prospectively recruited 320 patients with solitary radiopaque renal stones <15 mm in size. Patients were randomized to receive one of four shockwave protocols: (1) standard protocol (no ramping or pause); (2) ramping protocol alone; (3) ramping and pause protocols; or (4) pause protocol alone. Spot urine samples were collected before and for 2 years after treatment to monitor the levels of the renal fibrosis marker procollagen III aminoterminal propeptide (PIIINP) by blinded research staffs. Blood pressure and serum creatinine levels were also monitored during follow-up. The four groups had comparable baseline data and treatment parameters. Significant increases (p < 0.05) in the urinary PIIINP levels from 6 weeks until 18 months after SWL were observed among all patients and in individual groups. PIIINP levels peaked at 1 year after SWL and gradually decreased to the baseline at 2 years. At the 2-year follow-up point, the overall serum creatinine levels remained significantly elevated (76.21-80.01 μmol/L, p < 0.001). Twenty (9.95%) patients developed new-onset hypertension and another 43 (36.4%) experienced worsening blood pressure control. However, no differences were observed among the four treatment groups. SWL led to significant increases in renal fibrosis marker levels for up to 18 months after treatment. However, no differences in changes in renal fibrosis marker and serum creatinine levels and worsening of blood pressure control were observed with respect to the use of either ramping or pause treatment protocols.

MP54-17 A PROSPECTIVE STUDY ON THE EFFECT OF SHOCKWAVE LITHOTRIPSY ON RENAL FIBROSIS

You have accessJournal of UrologyStone Disease: Shock Wave Lithotripsy1 Apr 2016MP54-17 A PROSPECTIVE STUDY ON THE EFFECT OF SHOCKWAVE LITHOTRIPSY ON RENAL FIBROSIS Chi-Fai Ng, Sylvia Luke, Chi-Hang Yee, Kim Lee, John Yuen, and Danny Gohel Chi-Fai NgChi-Fai Ng More articles by this author , Sylvia LukeSylvia Luke More articles by this author , Chi-Hang YeeChi-Hang Yee More articles by this author , Kim LeeKim Lee More articles by this author , John YuenJohn Yuen More articles by this author , and Danny GohelDanny Gohel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.587AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There was limited information on the effect of shockwave lithotripsy (SWL) on renal fibrosis. Therefore, we investigate the effect of SWL on renal fibrosis, using urinary procollagen III aminoterminal propeptide (PIIINP) level as a surrogate marker for renal fibrotic process, in human subjects after one section of SWL. Moreover, the role of two renal protective protocols, low-energy shockwave pretreatment protocol and pause-protection protocol, on renal fibrotic process would also be assessed. METHODS 320 patients with a solitary radiopaque renal stone < 15mm, were recruited prospectively for this study. Patients were randomized to receive one of four shockwave (SW) protocols: (1) receiving 80% power (19.2 kV) from beginning until the end of treatment; (2) receiving the first 100 SWs at 40% power (9.6 kV), followed by SWs at 80% power until the end of treatment; (3) receiving 100 shocks at 40% power, followed by a 3-minute pause and then further SWs at 80% power until the end of treatment; and (4) receiving 100 shocks at 80% power, followed by a 3-minute pause and then further SWs at 80% power until the end of treatment. Spot urine samples were collected before and after treatment for two year, for marker measurement. RESULTS Baseline information and treatment parameters of the four groups were comparable. There was no difference between the baseline PIIINP levels among the four treatment groups. There was a significant rise in PIIINP level from 6-weeks until 18 months after SWL for the whole group, as well as individual groups (p<0.05). The level of PIIINP reached a peak at 1-year after SWL and then gradually came back to baseline level at 2-year after SWL. (Figure 1) CONCLUSIONS SWL resulted in a prolonged increase in renal fibrotic process, which was similar in patients treated with different protective treatment protocols. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e733 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Chi-Fai Ng More articles by this author Sylvia Luke More articles by this author Chi-Hang Yee More articles by this author Kim Lee More articles by this author John Yuen More articles by this author Danny Gohel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease

ObjectivesFibrosis is a predominant feature of IgG4-related disease (IgG4-RD). B-cell depletion induces a prompt clinical and immunological response in patients with IgG4-RD, but the effects of this intervention on fibrosis...

Evaluation of Serum Procollagen Aminoterminal Propeptide III, Laminin, and Hydroxyproline as Predictors of Severe Fibrosis in Patients with Chronic Hepatitis C

In an attempt to identify biochemical analytes that could enhance the discrimination between the patients with severe liver fibrosis (F3‐F4) and mild fibrosis (F1‐F2) based on absolute values of biochemical markers, we measured 12 analytes, including procollagen III aminoterminal propeptide (PIIINP), laminin, proline, hydroxylproline, glycine, AST, ALT, alkaline phosphatase, albumin, total bilirubin, total protein, and prothrombin time in 252 individuals with chronic hepatitis C infection (CHC). PIIINP and laminin were determined by radio‐immunoassay; the degraded amino acids were determined using high performance liquid chromatography. Statistical analyses were performed by logistic regression, and receiver operating characteristic (ROC) curves. The best linear combination of blood markers was selected by multivariate discriminant analysis (MDA) for construction of the fibrosis discriminant score (FDS). FDS, an index of five markers (PIIINP, laminin, hydroxyproline, prothrombin activity, and AST/ALT) correctly classified 82% of the patients with severe liver fibrosis at a discriminant cut‐off score=−0.5 (i.e., less than −0.5 indicated severe liver fibrosis and greater than −0.5 indicated mild liver fibrosis with sensitivity (76%) and specificity (89%). This result was reproduced in a validation study with no significant difference. In conclusion, FDS is useful for identifying severe liver fibrosis in patients with CHC.

Pravastatin therapy increases procollagen I N-terminal propeptide (PINP), a marker of bone formation in post-menopausal women

Background: The aim of our study was to evaluate whether pravastatin treatment affected biochemical markers of bone turnover. Methods: Thirty-six hypercholesterolemic post-menopausal women, not on hormonal replacement therapy, were selected from a population study evaluating factors affecting cholesterol response to pravastatin. After a 6-week period on a 30% fat diet, participants received treatment with 20 mg/day of pravastatin during a 16-week follow-up period. Pre- and post-treatment samples were analyzed for procollagen I aminoterminal peptide (PINP) and bone alkaline phosphatase (bAP) as markers of bone formation, carboxyterminal telopeptide of collagen I (CTX) as a marker of bone resorption, and procollagen III aminoterminal propeptide (PIIINP) as a marker of fibrogenesis. Results: Total cholesterol decreased from 7.26±0.83 to 6.1±0.77 mmol/l with pravastatin treatment. PINP levels significantly increased (from 33.6±13 to 37.4±16, p=0.03) without changes in bAP or CTX. Individual changes in PINP correlated with individual reduction in cholesterol levels ( r=0.337, p=0.04). There was no significant change in PIIINP concentration. Conclusions: Pravastatin treatment increased PINP levels, a marker of bone formation, in hypercholesterolemic, post-menopausal women, without affecting bone resorption. PIIINP concentration, a marker of liver fibrogenesis, was not affected by the treatment.

Alveolar lavage fluid (ALF) of normal volunteer subjects: cytologic, immunocytochemical, and biochemical reference values

Objective: Pooled bronchoalveolar lavage fluid (BALF), the return of lavage, contains both bronchial and alveolar material which differ from each other. Artifacts may be created by filtering, centrifuging and washing cells before cytopreparation. This study presents reference values of healthy volunteers for the alveolar sample, ALF, cytopreparation being performed without filtration or centrifugation. Methods: Eighteen healthy, non-smoking volunteers underwent a standard bronchoalveolar lavage using 10 aliquots of 20 ml of saline. Excluding the return of the first and second aliquots, the rest were pooled and examined cytologically, immunocytochemically and biochemically. The mean, standard deviation, and 95% confidence limits were calculated for the following variables: amount of return, estimated content of epithelial lining fluid (ELF), total and differential cell counts on filter and cytocentrifuge (CCF) preparations, computed cell counts per unit volume of ALF, distribution of lymphocyte subgroups CD3 + CD2, CD4, CD8, CD19, CD25 and CD57, and the ratio of CD4 to CD8, the amounts of lymphocytes in the same subgroups per volume of ALF, and the concentrations of total protein, albumin, immunoglobulins A, G and M, hyaluronic acid, eosinophilic cationic protein (ECP), procollagen III aminoterminal propeptide (PCP) and β 2-microglobulin in ALF and in ELF, as well as the ratios of the concentrations of the solutes in ALF to the same in serum. Results: The 95% confidence limits of means for the most important variables were as follows: estimated ELF content 0·42–0·74%; total cells in ALF 76·6–143·0 × 10 61 −1; distribution of inflammatory cells on filter and CCF slides: macrophages 74·9–83·6 and 81·4–90·1%, lymphocytes 13·1–22·5 and 8·1–16·4%, and neutrophils 1·0–4·1 and 0·7–2·7%, respectively; distribution of lymphocyte subsets: CD3 + CD2 85·6–90·6%, CD4 44·3–53·1%, CD8 26·9–35·8%; concentration of solutes in ALF: total protein 44·8–61·3 mg l −1, albumin 15·4–22·2 mg l −1, IgA 1·8–3.4 mg l −1, IgG 3·1–6·1 mg l −1, IgM 0·05–0·26 mg l −1, hyaluronic acid 8·8–11·1 μg l −1, ECP 0·19–0·77 μg l −1, PCP 0·005–0·058 μg l −1, β 2-microglobulin 62·2–81·5 μg l −1. Conclusions: Our results show that excluding the bronchial sample from ALF of volunteer subjects and omitting filtering and washing before cytopreparation produces cytologic, immunocytochemical and biochemical reference values with reasonable 95% confidence limits to be used in clinical settings.

Collagen III aminoterminal propeptide in gingival crevicular fluid before and after periodontal treatment.

The amount of procollagen III aminoterminal propeptide (PIIINP) in crevicular fluid (CF) was measured from three periodontitis patients before treatment (scaling, root planing, and curettage) and 2, 5, 10, 20, and 40 days after treatment. CF was collected by placing two paper strips in each pocket for 5 s, after which the amount of fluid was measured. Control samples were collected from three subjects with minimal gingival inflammation. PIIINP was extracted into saline solution and determined by a radioimmunological method. Plaque Index, Papilla Bleeding Index, and pocket depth were recorded before and 40 days after treatment. Forty days after treatment clinical parameters indicated healing. The CF PIIINP mean concentration was 162 micrograms/l (range 0-430) in the pretreatment samples. Ten days after treatment, PIIINP mean concentration was 1400 micrograms/l (range 1000-9000). After this, the concentration gradually decreased, reaching the pretreatment level 40 days after treatment. Most of the control samples showed undetectable amounts of PIIINP. It was suggested that elevated PIIINP concentrations in CF after periodontal treatment reflected increased type III collagen synthesis in gingiva. PIIINP concentrations before treatment reflected the rate of type III collagen turnover in inflamed periodontal tissues. It was further suggested that CF PIIINP has clinical value as an indicator of the healing process of inflamed gingiva.

Serum Concentrations of Extracellular Matrix Components

Laminin, hyaluronic acid (HA), procollagen III amino-terminal propeptide (PIIINP), and procollagen I carboxy-terminal propeptide (PICP) concentrations were measured by radioimmunoassay or radiometric assay in sera from 21 patients with glycogen storage disease (GSD). Laminin was increased in 16 of 29 samples from the six children with GSD I, 25/43 from the seven with GSD III, and 3/19 from the eight with GSD IX; laminin correlated with serum aspartate aminotransferase and gamma-glutamyltransferase but not with serum triglycerides, cholesterol, lactate, or urate. HA was increased in 20% of samples from GSD I, 58% from GSD III, and in none from GSD IX; HA correlated with serum lactate and urate but not with liver function tests, serum cholesterol, or triglycerides. Serum PIIINP was increased in only eight samples and PICP in only one; children with poor linear growth had low PIIINP and PICP. Immunostaining studies of nine liver biopsies taken at diagnosis showed increased laminin and PIIINP staining in portal tracts, fibrous septa, and around sinusoids in periportal regions; children with a greater degree of immunostaining did not always show significantly higher values of serum laminin or PIIINP. We speculate that raised serum laminin may reflect fibrogenesis (but not necessarily established fibrosis) in response to tissue damage in GSD, raised HA may reflect disturbed sinusoidal endothelial cell function, and low PIIINP and PICP impaired somatic growth rather than intrahepatic pathology.

Serum Concentrations of Extracellular Matrix Components

SummaryLaminin, hyaluronic acid (HA), procollagen III amino‐terminal propeptide (PIIINP), and procollagen I carboxy‐terminal propeptide (PICP) concentrations were measured by radioimmunassay or radiometric assay in sera from 21 patients with glycogen storage disease (GSD). Laminin was increased in 16 of 29 samples from the six children with GSD I, 25/43 from the seven with GSD III, and 3/19 from the eight with GSD IX; laminin correlated with serum aspartate aminotransferase and γ‐glutamyltransferase but not with serum triglycerides, cholesterol, lactate, or urate. HA was increased in 20% of samples from GSD I, 58% from GSD III, and in none from GSD IX; HA correlated with serum lactate and urate but not with liver function tests, serum cholesterol, or triglycerides. Serum PIIINP was increased in only eight samples and PICP in only one; children with poor linear growth had low PIIINP and PICP. Immunostaining studies of nine liver biopsies taken at diagnosis showed increased laminin and PIIINP staining in portal tracts, fibrous septa, and around sinusoids in periportal regions; children with a greater degree of immunostaining did not always show significantly higher values of serum laminin or PIIINP. We speculate that raised serum laminin may reflect fibrogenesis (but not necessarily established fibrosis) in response to tissue damage in GSD, raised HA may reflect disturbed sinusoidal endothelial cell function, and low PIIINP and PICP impaired somatic growth rather than intrahepatic pathology.

Serum Hyaluronic Acid and Procollagen III Amino Terminal Propeptide in Chronic Renal Failure

Elevated serum concentrations of hyaluronic acid (HA) and procollagen III amino terminal propeptide (PIIINP) have been found in various diseases characterized by altered metabolism of collagen. In the present study, their serum levels were measured in 105 renal patients and 22 normal controls. Median HA concentrations were 23 micrograms/l in controls, 47 micrograms/l in patients with chronic renal failure (CRF, not on dialysis; p less than 0.001), 75 micrograms/l on CAPD (p less than 0.001) vs. controls, p = 0.045 vs. CRF), and 167 micrograms/l on hemodialysis (p less than 0.001 vs. controls, CRF, and CAPD), respectively. The values correlated positively with age but not with renal function or the type of renal disease. In hemodialysis patients, HA correlated with the duration of renal replacement therapy and serum beta 2-microglobulin but not with serum alkaline phosphatase or C-terminal parathormone. Serum HA did not change significantly during hemodialysis treatment and was independent of the type of dialyzer membrane material. Median PIIINP values were 2.7 micrograms/l in controls, 4.4 micrograms/l in patients with CRF (p less than 0.001), 6.9 micrograms/l on CAPD (p less than 0.001 vs. controls, p = 0.022 vs. CRF), and 8.6 micrograms/l on hemodialysis (p = 0.001 vs. controls, NS vs. CRF or CAPD). Values correlated with HA only in patients on CAPD but they did not correlate with age, renal function or duration of renal replacement therapy. It is concluded that renal failure, especially long-term dialysis treatment, is associated with elevated serum concentrations of HA and--to a minor degree--PIINP. Thus, they may be a sign of altered connective tissue metabolism in patients on long-term dialysis.