Synthesis of type I collagen in healing wounds in humans.

To quantify wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube for 7 postoperative days and their concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured with specific radioimmunoassays. The mean concentration of PICP in would fluid on day 1 was 207 +/- 92 (SD) micrograms/L, and on day 2 908 +/- 469 micrograms/L (p less than 0.001, signed rank test). On day 7, the mean concentration reached was 380 times higher than that of day 1 (79,330 +/- 54,151 micrograms/L). Only one peak of PICP antigenicity, corresponding to the intact propeptide as set free during synthesis of type I procollagen, was detected on Sephacryl S-300 gel filtration analysis of wound fluid samples. The mean concentration of PIIINP was 70 +/- 61 micrograms/L on day 1, 86 +/- 88 micrograms/L on day 2, and 180 +/- 129 micrograms/L on day 3 (p less than 0.001 when compared with day 1). Finally on day 7, a 250-fold concentration (17,812 +/- 9839 micrograms/L), compared with day 1, was reached. Methods described in the present paper allow separate and repetitive quantification of the synthesis of both type I and type III procollagen during human wound healing.     

Synthesis of collagen types I and III in reincised wounds in humans

The problem of the biochemical quantification of long term human wound healing was approached by measuring collagen synthesis in reincisions using specific radioimmunoassays for the wound fluid concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP). First-day wound fluid PICP concentration after reincising a 3 week old scar was 25 times higher than the mean value in 20 reference standard incisions but scars older than 3 months did not show this difference. Wound fluid taken in subsequent days demonstrated that the initial acceleration of synthesis disappeared by the fourth day. When wound fluid PIIINP was assessed, high concentrations were found in reincisions of wounds for up to 5 months after the previous operation. The acceleration was also lost more slowly during the first postoperative week. The duration of a high rate of type I collagen synthesis compares well with studies in experimental wounds which show increased gain of strength if they are made not more than 6 weeks after previous surgery. The longer activity of the metabolism of type III collagen related antigens could reflect their function in the regulation of collagen fibril formation.     

Markers of collagen synthesis and degradation in urogenital tissue from women with and without stress urinary incontinence

AIMS: Multiparity and obesity are risk factors for stress urinary incontinence (SUI), but collagen synthesis and metabolism in the urogenital tissue itself may also affect its function and control of micturition. Whether changes in synthesis or degradation of collagen are part of the etiology of SUI is not known and published studies show diverging results. The aims of the present study was to investigate collagen turnover in urogenital tissue in women with SUI (n=71) and in urologically healthy women (n=31). METHODS: Markers of collagen synthesis and breakdown, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP), and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and peripheral serum. RESULTS: In the total clinical material SUI patients were significantly older, had a significantly higher body mass index (BMI) and significantly lower serum PICP and tissue ICTP levels than the controls. When healthy controls were compared with SUI patients matched for age, BMI, parity, and hormonal/menopausal status (31 women in each group), the SUI patients had significantly lower serum concentrations of PICP and significantly lower tissue concentrations of PIIINP and ICTP than the controls. Within the total material of SUI patients, post-menopausal women with weak and strong HRT and pre-menopausal women had significantly lower S-ICTP concentrations than untreated post-menopausal patients. Significant negative correlations to parity were found for T-PIIINP and T-PICP and to BMI for T-ICTP. CONCLUSIONS: The low tissue collagen marker levels in women with SUI suggest a reduced collagen turnover, which may negatively affect tissue strength and elasticity.     

Rapid Induction of Meningeal Collagen Synthesis in the Cerebral Cisternal and Ventricular Compartments after Subarachnoid Hemorrhage

Summary. Procollagen propeptides in the lumbar CSF increase after subarachnoid hemorrhage (SAH), and elevated concentrations have been detected as early as on day 8. We studied here the timing and localization of the induction of meningeal collagen synthesis during the first week after SAH by analysing cisternal and ventricular CSF samples. We obtained 29 cisternal and 10 ventricular CSF samples at operation from patients with SAH between days 1 and 9 after onset. The carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured using radio-immunoassays. The concentrations of PICP and PIIINP in the cisternal CSF were elevated as early as on day 2 after SAH. PICP increased in a sigmoidal fashion (R²=0.39, p<0.001), while PIIINP increased linearly (R²=0.28, p=0.003) and was approximately 3-fold higher on day 9 than initially. PICP was twice as high (p=0.02) in the cisternal than in the ventricular CSF after SAH and PIIINP was 4-times higher (p=0.007). Interestingly, the concentrations were similar in a patient with intraventricular bleeding. The cisternal compartment contributed to the propeptides in the CSF more than did the ventricular compartment, but the latter also appeared to have a definite potential for fibroproliferative reaction. Meningeal collagen synthesis was induced rapidly within the first few days after SAH suggesting that therapeutic attempts to inhibit the fibroproliferative reaction should be started as early as possible.     

Effect of jaundice and its resolution on wound re-epithelization, skin collagen synthesis, and serum collagen propeptide levels in patients with neoplastic pancreaticobiliary obstruction

BACKGROUND: Wound and anastomotic healing is considered to be delayed in patients with obstructive jaundice. The study was designed to find out whether the healing of experimental suction blister wounds, skin collagen synthesis, and serum procollagen levels are affected by obstructive jaundice, and if biliary drainage may cause any alterations in these processes. PATIENTS AND METHODS: Suction blisters were induced on 24 patients with obstructive jaundice caused by neoplastic pancreaticobiliary obstruction and 17 control patients with the corresponding condition without jaundice, to compare healing parameters and collagen synthesis between the groups. A second set of suction blisters were induced on 13 formerly jaundiced patients after the resolution of jaundice and on 14 control patients, to find out whether drainage or time modifies healing or collagen synthesis. By using this model, it is possible to evaluate the re-epithelization and inflammation on wound healing and to assess the baseline skin collagen synthesis. The healing of suction blisters was followed up by measuring water evaporation and blood flow in the wound. Blister fluids and serum samples were collected to study collagen propeptides. RESULTS: Healing of the blister wound was unaffected by obstructive jaundice. Drainage had no effect on healing. The baseline synthesis of type I and type III collagen in the skin was decreased in jaundiced patients. Biliary drainage improved the synthesis. Serum type III procollagen propeptide levels were elevated in jaundiced patients, but began to normalize after drainage. CONCLUSION: Healing of an experimental blister wound is not disturbed by obstructive jaundice. The decreased baseline skin collagen synthesis is partly restored by the resolution of jaundice. The results indicate that cell protein synthesis is disturbed earlier than cell dynamics in obstructive jaundice. The elevated serum PIIINP levels, which are most likely to be related to early fibrosis in liver, decreased after drainage.     

Serology of abnormal fracture healing: the role of PIIINP, PICP, and BsALP

OBJECTIVE: To determine whether poorly healing tibial shaft fractures exhibit a serological response of bone-specific alkaline phosphatase (BsALP), collagen I carboxy-terminal propeptide (PICP), collagen III amino-terminal propeptide (PIIINP), and collagen I carboxy-terminal telopeptide (ICTP) different from that of normally healing fractures. DESIGN: Prospective. PARTICIPANTS: Twenty consecutive patients with isolated tibial shaft fractures with or without fracture of the fibula. MAIN OUTCOME MEASUREMENTS: Assays of BsALP, PICP, PIIINP, and ICTP were performed with serum samples taken at standard intervals from twenty-four hours to twenty weeks after fracture. Fracture healing was assessed at five, ten, fourteen, and twenty weeks for clinical and radiological evidence of union. RESULTS: Seventeen fractures united within the twenty-week study period. The three fractures exhibiting delayed union demonstrated significantly lower PICP levels and marginally lower BsALP levels at twenty weeks. PIIINP levels were significantly higher in these three fractures at ten weeks. There was no difference in ICTP between the seventeen united and the three ununited fractures. CONCLUSIONS: This study identified three serological features of a poor healing response in tibial shaft fractures. First, matrix collagen I and III production in the first ten weeks of healing was adequate, with evidence of significantly increased production of type III collagen. Second, there was no serological evidence of a deficient osteoblast response, as indicated by normal levels of BsALP and PICP, during this early period. Third, evidence of a deficient osteoblast response appeared only at twenty weeks after injury.     

Types I and III procollagen extension peptides in serum respond to fracture in humans

Summary Markers of types I and III collagen turnover were measured in serial blood samples in 16 patients with a Colles' fracture. The collagen markers were the carboxy-terminal extension peptide of type I procollagen (PICP) and the amino-terminal extension peptide of type III procollagen (PIIINP). Significant increases were found of PIIINP within 1 week and of PICP within 2 weeks. This sequential appearance of PIIINP and PICP was found to be in agreement with the appearance of types III and I collagen during early fracture healing as demonstrated in previous animal experimental studies. PICP had levelled off after 9 months, whereas PIIINP remained elevated. Osteocalcin, a serum marker of osteoblast activity, increased within 1 week and levelled off after 9 months. Correlations betwen the change in osteocalcin and those in PICP and PIIINP, respectively, were weak. These new biochemical markers may prove relevant as non-invasive markers of normal and pathological fracture healing in humans.     

Aminoterminal propeptide of type III procollagen in serum during wound healing in human beings

The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum as an indicator of tissue repair was studied in 71 surgical patients undergoing minor, moderate abdominal, major abdominal, or hip surgery. An increase in serum PIIINP concentrations took place within the first week, and its magnitude was related to the extent of the soft-tissue operations. After the hip replacement, the maximum PIIINP concentration was reached somewhat later. Very high levels of serum PIIINP were seen in three patients with serious wound infections. The serum PIIINP antigenicity consisted both before and after surgery of equal proportions of two forms, one corresponding to the propeptide as set free during synthesis of new collagen and the other being larger and probably derived from turnover of type III collagen fibers. The proportion of the latter form was accentuated in infection. In contrast, in the wound the form derived from synthesis of type III collagen predominated. These results suggest that the postoperative increase in serum PIIINP levels is partly the result of tissue repair and partly the result of whole-body turnover of type III collagen.     

Endocrine status and markers of collagen synthesis and degradation in serum and urogenital tissue from women with and without stress urinary incontinence

AIMS: To investigate possible differences in androgen/estrogen status between patients with stress urinary incontinence (SUI) and healthy women's and to study possible associations between circulating estrogens and androgens on the one hand and collagen synthesis and metabolism in urogenital tissue on the other. METHODS: Markers of collagen turnover, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP), and the amino-terminal propeptide of procollagen III (PIIINP), were assayed in urogenital tissue homogenates and estradiol-17beta (E2), total testosterone (T), and sex-hormone-binding globulin (SHBG) were assayed in peripheral serum from 58 patients with SUI and 30 urologically healthy women. Apparent concentrations of free testosterone (fT) were calculated from T, SHBG, and a fixed albumin value. RESULTS: Significant positive correlations were found between E2 and PICP in controls and between E2 and ICTP in SUI patients without exogenous hormones. Significant negative and sometimes strong correlations were found between serum T and fT on the one hand and all three collagen turnover markers on the other. These correlations were strengthened when parity and/or body mass index (BMI) were reduced. No correlations between T and fT and collagen turnover markers were found in the controls. There were no significant differences between any of the groups in serum E2, T, or fT. CONCLUSION: Estrogens may increase collagen turnover in urogenital tissue, however, the clinical significance of this is still unclear. Androgens may affect urogenital tissue negatively by slowing down collagen turnover, probably by inhibition of matrix metalloprotease (MMP) synthesis and/or activity. Urogenital tissue in SUI patients and in urologically healthy women may differ in androgen sensitivity.     

Aminoterminal propeptide of type III procollagen in healing wound in humans.

For quantitative analysis of wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube and their concentration of the aminoterminal propeptide of type III procollagen was measured with a specific radioimmunoassay. Peritoneal fluid, collected through an abdominal drain, and serum were also analyzed. At day 1 after operation, the mean concentration of the propeptide was 30 times higher than the mean preoperative serum level (2.5 micrograms/L). A significant increase (p less than 0.001) occurred at day 3 in the wound and at day 2 in peritoneal fluid. At day 5 the mean wound concentration (2670 micrograms/L) was 1000 times higher than the serum level. In serum a small but significant increase (p less than 0.05) was found at days 5 and 30. The increase in wound fluid resulted from the intact, liberated propeptide, indicating that the results reflect the synthesis of type III collagen deposited in the wound. This procedure offers a quantitative tool for wound healing studies. Other extracellular matrix components can also be measured, the sequential pattern of their appearance can thus be assessed, and disturbances and treatment effects in wound healing can be detected.     

Changes in collagen metabolites in serum after cemented hip and knee arthroplasty

Summary Markers of types I and III collagen turnover were measured in serial blood samples collected preoperatively and 60 days after surgery in 13 patients undergoing cemented total hip arthroplasty and 11 patients undergoing cemented total knee arthroplasty. The markers were the carboxyterminal extension peptide of type I procollagen (PICP) and the aminoterminal extension peptide of type III procollagen (PIIINP). The course of serum PICP and serum PIIINP in the two treatment groups were uniform. Serum PICP showed an initial fall on day 4, thereafter increasing up to days 14–28 and was still elevated on day 60. Serum PIIINP was increased on day 4, reaching its maximum on days 14–21, and thereafter declined but remained elevated above initial values. Serum osteocalcin, a serological marker of osteoblast activity, showed no significant changes in the two treatment groups during the observational period. We suggest that the changes in serum PICP and serum PIIINP reflect collagen formation in healing soft connective tissue 60 days after cemented hip or knee arthroplasty.     

Are Bone Turnover Markers Capable of Predicting Callus Consolidation During Bone Healing?

The aim of this study was to determine the ability of the following bone turnover markers to monitor the course of callus consolidation during bone healing: Carboxy-terminal propeptide of procollagen type I (PICP), skeletal alkaline phosphatase (sALP), and amino-terminal propeptide of type III procollagen (PIlINP). Since interfragmentary movements have been proven to possess the ability to document the progression of bone healing in experimental studies, correlations between bone turnover markers and interfragmentary movements in vivo were investigated. Therefore, two different types of osteosyntheses representing different mechanical situations at the fracture site were compared in an ovine osteotomy model. Blood samples were taken preoperatively and postoperatively in weekly intervals over a nine-week healing period. At the same intervals, interfragmentary movements were measured in all sheep. After nine weeks, animals were sacrificed and the tibiae were evaluated both mechanically and histologically. Wide interindividual ranges were observed for all bone turnover markers. The systemic PICP level did not increase with callus consolidation. The bone-healing model seemed to influence the systemic level of PIIINP and sALP but no general correlation between bone turnover markers and interfragmentary movements could be detected. No differences between the different types of osteosyntheses and thus the different mechanical situations were observed. All analyzed markers failed as general predictors for the course of callus consolidation during bone healing.     

Collagen types I and III propeptides as markers of healing in chronic leg ulcers. A noninvasive method for the determination of procollagen propeptides in wound fluid--influence of growth hormone.

A noninvasive method allowing measurements of the propeptides of collagen type III (PIIINP) and type I (PICP) in ulcer washings was developed. The response to topical human growth hormone was examined. Fourteen patients with venous ulcers were treated sequentially with human growth hormone (0.1, 0.25, and 1 IU/cm2/day), each dose for 1 week, followed by 1 week washout. On alternate days, three and two times during treatment and washout periods, respectively, the ulcers were washed and incubated for 30 minutes with sterile water. No changes in healing rates in relation to growth hormone application were observed. In contrast, PIIINP increased significantly to 168% (154% to 184%) (mean, 95% confidence interval) and 195% (179% to 218%) 5 and 9 days, respectively, after start of treatment, (p < 0.01). Propeptides of collagen type I reached a significant increase, to 196% (172% to 232%), in the fourth week, (p < 0.01). The areas under the curves of PICP and PIIINP correlated significantly with the healing rates (r = 0.57, p = 0.04; and r = 0.64, p = 0.01, respectively). The authors conclude that propeptide measurements may be useful markers of healing in clinical studies.     

Collagen type I metabolism after bone surgery

This study follows the postoperative course of serum collagen type I metabolites in patients after uncomplicated implantation of a cemented total hip endoprothesis (TEP; n = 12, mean age: 69.3 years), a cemented hemiendoprothesis (HEP; n = 13, mean age 79.7 years), a dynamic condylar or hip screw (DCS/DHS; n = 12, mean age 75.1 years) and osteosynthetic treatment of a Weber B or C fracture (OS; n = 17, mean age 54.3 years). The course of the propeptide of human type I procollagen (PICP) as an anabolic marker as well as of I-carboxyterminal telopeptide (ICTP) as a catabolic marker of bone metabolism was characterized. Measurements were done preoperatively and weekly for 3 weeks after surgery. The concentrations of both markers increased and reached a maximum in the 2nd or 3rd week after surgery. However, the PICP values differed, depending on the kind of surgical intervention and the type of bone healing. Secondary fracture healing with formation of callus occurred in the DCS/DHS group, which developed the highest median PICP concentrations (initial 83 μ g/l, second week 337 μg/l; P < 0.001). In contrast, the primary bone healing in the OS group showed increasing ICTP but unchanged PICP concentrations. Patients in the cemented TEP and HEP groups as a kind of artificial bone healing had comparable concentrations. To consider the effective metabolism of collagen type I, the PICP/ICTP ratio was calculated. Although the median PICP and ICTP concentrations of the studied groups differed, the PICP/ICTP ratios were similar. In comparison to 54 young and healthy volunteers (median PICP/ICTP ratio: 37), the ratios of the studied groups were still normal but low (median ratios: < 20). This could be an effect of decreasing collagen type I metabolism with age. Although the results are in agreement with animal studies and histomorphometric investigations, the clinical use of PICP and ICTP determination as a tool for the detection of complicated bone healing is limited by the marked interindividual variability and the uncertain bone specificity. Received: 2 April 1998     

Do serological tissue turnover markers represent callus formation during fracture healing?

Serological parameters of bone and fibrous tissue turnover were demonstrated to monitor the course of fracture healing. The aim of this study was to evaluate the correlation between the serological parameter levels during fracture healing and callus development in a standardised ovine model of fracture healing. Two years old female sheep received a standardised 3 mm tibial bone defect stabilised by an external fixator. The serological levels of the C-terminal propeptide of procollagen type I (PICP), bone specific alkaline phosphatase (bALP), total alkaline phosphatase (tALP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), calcium, phosphate and the N-terminal peptide of procollagen type III (PIIINP) were observed over a 9-week healing period. The course of fracture healing was monitored radiographically, and the callus composition was evaluated histologically at 2, 3, 6 and 9 weeks post-surgery. The serological results were compared with an untreated control group. Additionally, the maximum values during healing were compared with juvenile values to gauge the level of the serological response. The histological and radiographical results demonstrated callus formation without complications. All serological parameters showed broad inter-individual variations, and the response to the standardised fracture scenario was strongly individual. Maximum values during fracture healing did not reach the juvenile levels. The fractured as well as the control animals showed significant changes in the parameter levels. No correlations were observed between the histological course of healing and the course of bone formation markers whilst the TRAP level was reduced during bony callus formation. The PIIINP level increased when the amount of soft callus tissue decreased during healing. The observed bone formation markers were not suitable as general markers to detect the course of fracture healing, whilst PIIINP was able to reflect soft callus degradation.     

Increased amount of type III pN-collagen in AAA when compared with AOD.

OBJECTIVE: the extent of the processing of type III procollagen to type III collagen was determined in nine human abdominal aortic aneurysms (AAA), and compared with ten samples of aortoiliac occlusive disease (AOD). METHODS: the aminoterminal propeptide (PIIINP) and telopeptide (IIINTP) of type III procollagen and collagen, respectively, were immunologically measured in the soluble and insoluble fractions of the extracellular matrix. The assay for PIIINP in the insoluble matrix was further validated. RESULTS: the insoluble matrices of AAAs contained at least 12 times more incompletely processed type III pN-collagen than AOD specimens (0.74% and 0.061%, respectively). Also, the soluble extracts of AAAs tended to contain more non-processed type III pN-collagen than free, properly cleaved aminoterminal propeptide. CONCLUSIONS: the larger amount of type III pN-collagen suggests an alteration in the metabolism of type III collagen in AAAs. This may partially explain the decreased tensile strength of the aortic tissue.     

血小板源伤口愈合因子促糖尿病大鼠伤口组织胶原合成机制的研究

目的 探讨外源性血小板源伤口愈合因子（PDWHF）促糖尿病大鼠伤口合成胶原与内源性转化生长因子-β（TGF-β1）基因表达的关系。方法 33只雄性SD大鼠,分为正常组（A组n＝9）、糖尿组（n＝24）。四氧嘧啶诱导糖尿病组大鼠血糖值大于1．8g/L1、2天后,在每组大鼠背部造成两块直径为1．8 cm的全层皮肤伤口。术后当天及以后连续6天,每天一次,糖尿病组大鼠一侧伤口局部应用PDWHF（100μg/伤口）作为治疗组（B组）,另一侧伤口作为对照组（C组）。斑点杂交法测定伤后不同天数伤口组织中TGF－β1、Ⅰ型（α1）前胶原mRNA水平量。结果 伤后5、7天,B组伤口组织TGF－β1mRNA水平量是C组的4倍和5．6倍,经统计学处理有非常显著性差异（P＜0．01）,但低于A组（P＜0．05）;伤后10天,三组间TGF-β1mRNA水平量无明显差异。伤后5、7天及10天,B组I型（α1）前胶原mRNA水平量明显高于C组,分别为2．1、1．8和2．3倍有非常显著性差异（P＜0．01）;但伤后5、7天仍明显低于A组（P＜0．05）,伤后10天,两组间差异消失。结论 PDWHF促进糖尿病大鼠伤口内源性TGF－β1基因表达是其增强I型（α1）前胶原合成的重要原因。     

Dose-response effect of short-term calcitriol treatment on bone and mineral metabolism in normal males

To evaluate the effects of short-term treatment with calcitriol on biochemical markers of calcium and bone metabolism, 36 normal male volunteers (aged 21–54 years) were randomized to oral treatment for 7 days with either (A) calcitriol, 1 μg twice daily, (B) calcitrol, 0.5 μg twice daily, or (C) placebo twice daily. Serum calcium increased slightly in a dose-dependent manner (maximal increase 2.5%, p < 0.05) followed by a heavy increase in both 24 h (max. 156.1%, p < 0.001) and fasting urinary calcium excretion (max. 123.1%, p < 0.001), and a striking reduction in serum PTH (max. −43.1%, p < 0.001). Biochemical markers of osteoblast activity and bone formation increased immediately in a dose-dependent manner [serum osteocalcin (max. 37.8%, p < 0.03) and serum procollagen type I C-terminal propeptide (PICP) (max. 26.0%, p < 0.05)], whereas there was no effect on serum bone alkaline phosphatase. Calcitriol treatment had no effect on biochemical markers of bone resorption [serum C-terminal telopeptide of type I collagen (ICTP) and fasting urinary excretion of hydroxyproline/creatinine (OHP)]. Extraosseous collagen matrix synthesis was not affected evaluated by serum procollagen type III N-terminal propeptide (PIIINP). In the follow-up period (15 weeks) no unequivocal changes were observed. The fast and protracted increase in biochemical markers of osteoblast activity and bone formation, without affecting bone resorption and extraosseous connective tissue metabolism points toward a selective effect of calcitriol on bone matrix formation.     

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.     

The aminoterminal propeptide of type III procollagen and basement membrane components in serum during wound healing in man

The aim of this study was to investigate if the serum concentrations of antigens related to basement membrane components and to the interstitial type III collagen reflect the sequential and transitional synthesis of basement membranes and of type III collagen in wound granulation tissue. The aminoterminal propeptide of type III collagen, the 7S domain of type IV collagen and the P1 fragment of laminin were determined in 11, 10 and 6 patients, respectively, during wound healing following intraabdominal surgery. No change was observed in the type III propeptide level at the first postoperative day. During further follow-up (mean 71 days, range 21-155 days), the propeptide levels showed a transitional increase, with a maximum at day 10. A sequential pattern was observed in the increase of the serum concentrations, as the maximum increase of the basement related antigens in serum occurred within the first 7 postoperative days. This is in accordance with observations of an early formation of basement membranes in blood vessels, preceding deposition of interstitial collagens in granulation tissue. The results support the assumption that the serum concentrations of connective tissue related antigens may be valuable markers of wound healing in man.