Biomedical subjects

Juha Risteli

Publications and source records attributed to Juha Risteli.

At least 19 recordsLinked to original sources

PubMed2006

Pimecrolimus cream 1% in the treatment of lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin condition, which most commonly causes dysuria, pruritus and soreness of the vulval and perianal areas. Potent topical corticosteroids are used for the treatment of LS, but it is well known that they inhibit collagen synthesis and cause skin atrophy as a side effect. METHODS: The present pilot study evaluated the efficacy and safety of pimecrolimus cream 1% applied twice daily for up to 6 months in 29 women with severe LS. RESULTS: Of the 26 subjects who completed the follow-up period, 42% (11/26) were in complete remission with relief from itchiness, pain and inflammation. A 3.5-fold increase in type I collagen synthesis and a 7.5-fold increase in type III collagen synthesis of the affected areas was detected after 2 months of pimecrolimus treatment. There were no systemic adverse reactions, although mild local skin reactions were reported by 50% of the patients. Blood concentrations of pimecrolimus were checked in 10/26 patients (39%) and were undetectable in all cases. CONCLUSIONS: Patient-applied 1% pimecrolimus cream is safe and effective for the treatment of LS.

Adult↗

PubMed2006

Extracellular matrix proteins and myofibroblasts in granulomas of sarcoidosis, atypical mycobacteriosis, and tuberculosis of the lung.

Sarcoidosis, atypical mycobacteriosis, and tuberculosis are common diseases of human lung with a typical feature of formation of granulomas. The structure of granulomas has not been elucidated completely. We studied the expression of tenascin-C, precursor proteins of collagens I and III, and the presence of myofibroblasts in granulomas of sarcoidosis, atypical mycobacteriosis, and tuberculosis of human lung. Twenty-five histologic samples of lung were analyzed by immunohistochemistry using antibodies to tenascin-C and aminoterminal propeptides of collagens I and III. To identify the myofibroblast-type cells in granulomas, the sections were also stained with antibodies against alpha-smooth muscle actin, vimentin, and desmin. In every case, tenascin-C and precursor proteins of collagens I and III were expressed around granulomas. Precursor protein of collagen I was expressed also within them. In tuberculosis and atypical mycobacteriosis, expression of tenascin-C and precursor protein of collagen I was stronger than in sarcoidosis. The cells demarcating granulomas and, thus, colocalizing with tenascin-C and both collagen precursors were positive for alpha-smooth muscle actin and vimentin, which suggests that these cells are myofibroblasts. They were also more abundantly present in tuberculosis and atypical mycobacteriosis, as suggested by alpha-smooth muscle actin staining. We concluded that tenascin-C and precursor proteins of collagens I and III are expressed around granulomas in sarcoidosis, atypical mycobacteriosis, and tuberculosis of the lung; and furthermore, their expression colocalize with the expression of myofibroblasts. Our results further point to the fact that fibrogenesis and matrix turnover is stronger in tuberculosis and atypical mycobacteriosis than in sarcoidosis.

Actins↗

PubMed2006

Localization of precursor proteins and mRNA of type I and III collagens in usual interstitial pneumonia and sarcoidosis.

The aim of this study was to assess and compare the accumulation and distribution of newly synthesized type I and III collagens in usual interstitial pneumonia (UIP) and pulmonary sarcoidosis. Lung biopsies from 10 patients with UIP and 13 patients with sarcoidosis were investigated by immunohistochemical technique and mRNA in situ hybridization. The antibodies for the aminoterminal propeptide of type I procollagen and the aminoterminal propeptide of type III procollagen (PINP and PIIINP, respectively) were used. When compared to healthy lung, levels of type I pN- and type III pN-collagens were increased in both of these disorders. Type I procollagen was mostly present as intracellular spots in newly formed fibrosis in UIP while type III pN-collagen was expressed extracellularly underneath metaplastic alveolar epithelium. Type I procollagen was present intracellularly within and around the granulomas of sarcoidosis, whereas type III pN-collagen was expressed extracellularly, mainly around the granulomas. mRNAs of both collagens colocalized with the precursor proteins. We conclude that the expression of precursor proteins and mRNA of type I and type III collagens is increased in UIP and sarcoidosis, reflecting mainly active synthesis of these collagens in different areas of the lung.

Collagen Type I↗

PubMed2006

Type I and type III collagen synthesis and composition in the valve matrix in aortic valve stenosis.

Changes in the collagenous matrix may contribute to the pathogenesis and progression of human aortic valve stenosis (AS). To evaluate the significance of collagen I and III in the pathogenesis of AS, we studied their synthesis in diseased valves. Type I and type III collagen mRNA expression and the immunohistochemical localization of the collagen antigens were studied from 36 AS and 2 normal aortic valves. The concentrations of propeptides and telopeptide structure of type I (PINP, PICP, and ICTP) and those of III collagens (PIIINP and IIINTP) were measured by radioimmunoassays in soluble tissue extracts and trypsin-solubilized calcified and non-calcified matrices of 11 AS and 24 healthy aortic valves of different ages. The synthesis of type I collagen, localized in the myofibroblasts adjacent to calcified nodules, was two- to three-fold in the AS samples compared to the controls. The proportion of collagen in the total protein fraction was 90% in the healthy valves, 50% in the non-calcified matrix, and 10% in the calcified matrix of AS valves. In the calcified valves, the ICTP content was six-fold compared to the age-matched controls and two-fold compared to the young control group. In the controls, the amount of ICTP in type I collagen decreased with age (r=-0.908, p<0.001) and was replaced by other cross-linked C-telopeptide structure. The concentration of type III collagen decreased during aging (r=-0.753, p<0.001). The decrease in total collagen content, despite the increase in type I collagen synthesis indicates an increase in collagen turnover in AS. The calcification of the aortic valves is accompanied by increased amount of ICTP in type I collagen.

Adolescent↗

PubMed2006

Action of topical thyroid hormone analogue, triiodothyroacetic acid in reversing glucocorticoid-induced skin atrophy in humans.

The present study concerns the effect of topical treatment with a cream formulation of triiodothyroacetic acid (TRIAC) in comparison with a placebo preparation in producing a reversal of skin atrophy induced by long-term employment of topical glucocorticoid therapy in humans. A total of 39 patients with clinically verified skin atrophy due to long-term use of topical potent glucocorticoids were randomized. The changes in skin thickness, elastic fibers, and hyaluronic acid were evaluated by means of sonography and histology. After 8 weeks' treatment, the skin thickness measured by sonography increased by 16% in the epidermis, 8% in the dermis, and epidermis + dermis in the placebo group. In the TRIAC 0.1% group, the corresponding values were 24% ( p=0.063) in the epidermis, 28% ( p=0.042) in the dermis, and 25% ( p=0.039) in the epidermis + dermis. After 8 weeks, in the placebo group, the skin thickness measured by biopsy increased by 5% in the epidermis, epidermis + dermis, and 6% in the dermis. In the TRIAC 0.1% group, the corresponding values were 31% ( p=0.041) in the epidermis, 46% ( p=0.041) in the dermis and 44% ( p=0.043) in the epidermis + dermis. After 8 weeks, the elastic fibers of moderately irregular and thickened fibers increased by 56% in the placebo group and 100% ( p=0.043) in the TRIAC 0.1 group. This study indicates that topical treatment with TRIAC appears to reverse glucocorticoid-induced skin atrophy under the narrow conditions tested.

Administration, Topical↗

PubMed2005

Treatment of hypertrophic scars and keloids with a radiofrequency device: a study of collagen effects.

BACKGROUND AND OBJECTIVE: To determine the efficacy and safety of the ThermaCool TC radiofrequency system for treatment of hypertrophic and keloid scars and evaluate treatment associated collagen changes. MATERIALS AND METHODS: Six subjects with hypertrophic and four with keloid scars were treated with the ThermaCool device: one-third of the scar received no treatment (control), one-third received one treatment and one-third received two treatments (4-week interval). Scars were graded before and then 12 and 24 weeks after treatment on symptoms, pigmentation, vascularity, pliability, and height. Biopsies were taken from four subjects with hypertrophic scars and evaluated with hematoxylin and eosin (H & E) staining, multiphoton microscopy, and pro-collagen I and III immunohistochemistry. RESULTS: No adverse treatment effects occurred. Clinical and H & E evaluation revealed no significant differences between control and treatment sites. Differences in collagen morphology were detected in some subjects. Increased collagen production (type III > type I) was observed, appeared to peak between 6 and 10 weeks post-treatment and had not returned to baseline even after 12 weeks. CONCLUSION: Use of the thermage radiofrequency device on hypertrophic scars resulted in collagen fibril morphology and production changes. ThermaCool alone did not achieve clinical hypertrophic scar or keloid improvement. The collagen effects of this device should be evaluated further in order to optimize its therapeutic potential for all indications.

Adult↗

PubMed2005

Human mesenchymal stem cell derived osteoblasts degrade organic bone matrix in vitro by matrix metalloproteinases.

Some recent studies have suggested that cells of mesenchymal origin might participate in the organic bone matrix dissolution. In the present study, collagen synthesis and degradation by human mesenchymal stem cell (MSC) derived cells were studied at early stage of osteoblast differentiation using a special two-stage in vitro culture model. In this model, cells were cultured on bovine bone slices, which were first resorbed by osteoclasts. Synthesis of type I collagen was markedly enhanced when mesenchymal cells were cultured on bone matrix. After thorough osteoclast removal, MSC derived cells were capable of degrading the organic bone matrix, and caused a release of type I collagen degradation product (ICTP) into the culture medium. This was inhibited by matrix metalloproteinase (MMP) inhibitor, while cysteine proteinase inhibitor or estrogen had no inhibitory effect. Western blot analysis or gelatin zymography confirmed the presence of MMP-2, -8, -13 and -14, but not MMP-1 or -9, in the differentiated cells. 17beta-Estradiol was found to increase the expression of MMP-2 and -14 by these cells. Finally, scanning electron microscopy showed that the differentiating human MSCs were capable of degrading organic bone matrix remnants from the bottom of the resorption lacunae. These data support the hypothesis that collagen cleavage by the same cells that are subsequently responsible for bone formation is MMP mediated process and is an important step coupling bone formation into bone resorption.

Animals↗

PubMed2005

Anthropometrics and biochemical markers in men.

The relation between anthropometric components and biochemical markers has not been previously studied. To clarify the role of anthropometric factors in bone metabolism in men, 145 randomly selected subjects 40 to 70 yr of age from a population-based cohort were studied. Pearson's r and multiple regression analysis were used to assess the relation between anthropometrics (weight, body mass index [BMI], percentage of body fat, fat-free weight, and fat freeBMI), biochemical markers, and bone mineral density (BMD) at the spine and femoral neck, as well as between BMD and each biochemical marker (serum bone formation marker procollagen amino-terminal propeptide [PINP],urinary bone resorption marker amino-terminal telopeptide [NTx], and the ratio of PINP to NTx. Of the anthropometric factors, fat-free BMI had the highest association with the markers (r = -0.21 to -0.35, p < 0.05) and explained a higher percent of both spine BMD and NTx variance than weight. Body fat did not correlate with the BMD measures. Urinary NTx was a better indicator of current BMD status than PINP or the ratio of PINP to NTx, with the highest association with BMD at the sites tested (r = -0.20 to -0.29). NTx levels were statistically significantly different between men with normal and osteoporotic BMD at the femoral neck.

Absorptiometry, Photon↗

PubMed2005

Sensitive immunoassays for the autoantibodies reacting against citrullinated carboxy-terminal telopeptides of type I and type II collagens in patients with rheumatoid arthritis.

We developed sensitive assay methods for autoantibodies recognizing the citrullinated synthetic peptides derived from type I and type II collagens in patients with rheumatoid arthritis (RA). These peptides were tested with the chemiluminescence method (Nichols Advantage System). In 44 RA patients out of 120, the sera showed increased binding of citrullinated synthetic C-telopeptide derived from the alpha1 chain of type I collagen (p=0.003 compared to controls). For a corresponding C-telopeptide pair from the alpha1 chain of type II collagen, 35 patient sera bound the citrullinated peptide more strongly than the arginine peptide, but the difference compared to the controls was not significant (p=0.074). Correlation between the two carboxy-telopeptides was r=0.473 (p<0.001). The anti-CCP assay (antibodies against citrullinated filaggrin sequence-derived peptides) was positive in 59% of our RA patients. There was no relationship between the anti-CCP results and the antibodies against collagen C-telopeptides, but both are increased in RA patients. We demonstrated autoantibodies in RA patients that bound citrullinated C-telopeptides derived from type I and type II collagen antigens. The peptide sequences detected (-YYXA and -YMXA) were different from that based on the cyclic filaggrin antigen (-STXG-, where X represents citrulline).

Adult↗

PubMed2005

Estrogen responsiveness of bone formation in vitro and altered bone phenotype in aged estrogen receptor-alpha-deficient male and female mice.

OBJECTIVE: Although the beneficial effects of estrogen on bone are well known, the roles of estrogen receptors (ERs) in mediating these effects are not fully understood. METHODS: To study the effects of long-term ER alpha deficiency, bone phenotype was studied in aged ER alpha knockout (ERKO) mice. In addition, ERKO osteoclasts and osteoblasts were cultured in vitro. DESIGN AND RESULTS: Histomorphometric analysis showed that the trabecular bone volume and thickness were significantly increased and the rate of bone formation enhanced in both male and female ERKO mice in comparison to the wild-type animals. In ERKO males, however, the bones were thinner and their maximal bending strengths decreased. Consistent with previous reports, the bones of knockout mice, especially of female mice, were shorter than those of wild-type mice. In addition, the growth plates were totally absent in the tibiae of aged ERKO females, whereas the growth plate cartilages were detectable in wild-type females as well as in all the males. Analysis of cultured bone marrow cells from 10- to 12-week-old mice demonstrated that 17 beta-estradiol could stimulate osteoblastic differentiation of bone marrow cells derived from ERKO mice relatively to the same extent as those derived from wild-type mice. This was demonstrated by increases in synthesis of type I collagen, activity of alkaline phosphatase and accumulation of calcium in cultures. Total protein content was, however, reduced in ERKO osteoblast cultures. CONCLUSIONS: These results show altered bone phenotype in ERKO mice and demonstrate the stimulatory effect of estrogen on osteoblasts even in the absence of full-length ER alpha.

Animals↗

PubMed2004

Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio.

Previous reports indicate that mice deficient for cathepsin K (Ctsk), a key protease in osteoclastic bone resorption, develop osteopetrosis due to their inability to properly degrade organic bone matrix. Some features of the phenotype of Ctsk knockout mice, however, suggest the presence of mechanisms by which Ctsk-deficient mice compensate for the lack of cathepsin K. To study these mechanisms in detail, we generated Ctsk-deficient (Ctsk-/-) mice and analyzed them at the age of 2, 7, and 12 months using peripheral quantitative computed tomography, histomorphometry, resorption marker measurements, osteoclast and osteoblast differentiation cultures, and gene expression analyses. The present study verified the previously published osteopetrotic features of Ctsk-deficient mice. However, these changes did not exacerbate during aging indicating the absence of Ctsk to have its most severe effects during the rapid growth period. Resorption markers ICTP and CTX were decreased in the media of Ctsk-/- osteoclasts cultured on bone slices indicating impaired bone resorption. Ctsk-/- mice exhibited several mechanisms attempting to compensate for Ctsk deficiency. The number of osteoclasts in trabecular bone was significantly increased in Ctsk-/- mice compared to controls, as was the number of osteoclast precursors in bone marrow. The mRNA levels for receptor activator of nuclear factor (kappa)B ligand (RANKL) in Ctsk-/- bones were increased resulting in increased RANKL/OPG ratio favoring osteoclastogenesis. In addition, expression of mRNAs of osteoclastic enzymes (MMP-9, TRACP) and for osteoblastic proteases (MMP-13, MMP-14) were increased in Ctsk-/- mice compared to controls. Impaired osteoclastic bone resorption in Ctsk-/- mice results in activation of osteoblastic cells to produce increased amounts of other proteolytic enzymes and RANKL in vivo. We suggest that increased RANKL expression mediates enhanced osteoclastogenesis and increased protease expression by osteoclasts. These observations underline the important role of osteoblastic cells in regulation of osteoclast activity and bone turnover.

Animals↗

PubMed2004

Synthesis and maturation of type I and type III collagens in endometrial adenocarcinoma.

OBJECTIVE: The structure and distribution of type I and type III collagens in the extracellular matrix of malignant endometrium was evaluated for their roles in the development and progression of this neoplasm. STUDY DESIGN: Collagen synthesis and deposition in endometrial adenocarcinomas was determined by immunohistochemical analysis of type I and type III procollagen and verified by computer-assisted morphometry and in situ hybridization. RESULTS: In the stroma of well-differentiated adenocarcinomas increased intracellular collagen synthesis was observed in fibroblastic cells as well as increased extracellular formation of newly synthesized type I and type III procollagen. Collagen maturation was also rapid. In moderately differentiated tumors, destruction and dissolution occurred around invading islets, concomitantly with decreased deposits of both collagens, despite increases in corresponding mRNAs. In poorly differentiated neoplasms, solid epithelial islets coexisted with sparse and distinctly collagen-positive stroma. Poorly differentiated neoplasms also contained tumor cells exhibiting intracellular collagen staining as well as in situ hybridization signals. In highly malignant papillary adenocarcinomas, the tumor cells induced distinctly increased collagen synthesis and deposition of newly synthesized collagen but not the mature cross-linked protein. CONCLUSIONS: In malignancy, compression of surrounding stroma and a fibroproliferative response with increased collagen synthesis and deposition may prevent tumor growth. In more advanced lesions, stromal dissolution may permit tumor spread and in highly malignant lesions an abnormal stroma may promote neoplasm progression.

Adenocarcinoma↗

PubMed2004

Hexose sugars differentially alter collagen gene expression and synthesis in fibroblasts derived from granulation tissue, hypertrophic scar and keloid.

Clinical observations have suggested that sugar and honey enhance granulation tissue formation and in vitro studies have shown that monosaccharide sugars stimulate mesenchymal and endothelial cells. In this study, the effects of glucose, fructose, galactose and mannose on type I and type III collagen gene expression and synthesis were studied in granulation tissue, hypertrophic scar and keloid fibroblast cultures. Glucose elevated both type I and type III collagen mRNAs in hypertrophic scar fibroblasts. Fructose increased type III collagen mRNA almost sevenfold in granulation tissue fibroblasts. Galactose caused an increase in type I and type III collagen mRNAs in granulation tissue fibroblasts and hypertrophic scar fibroblasts but, in contrast, mannose decreased type I and type III collagen levels in hypertrophic scar and keloid fibroblasts. Analysis of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) revealed that glucose decreased the amount of PINP in granulation tissue and keloid fibroblasts, whilst fructose decreased the amount in all the fibroblast cell lines studied. Galactose caused a decrease in the synthesis of type I collagen in all cell lines but a decrease was seen in type III collagen only in hypertrophic scar fibroblasts. Mannose decreased the amount of PINP in all cell lines but a decrease in the amount of PIIINP was seen only in granulation tissue fibroblasts. The effect of sugars on the ratio type I/type III collagen was negligible or decreasing with the exception of galactose, which increased the ratio in hypertrophic scar fibroblasts. The results suggest that glucose, fructose and galactose have no significant value in the stimulation of collagen synthesis in vitro. Mannose may have value in the prevention or treatment of abnormal scars.

Cells, Cultured↗

PubMed2004

Type I and III collagen protein precursors and mRNA in the developing human lung.

Extracellular matrix proteins have a prominent role in both ontogenesis and fibrogenesis in the human lung. The aim of this study was to analyse the expression of newly formed precursor proteins and mRNA of collagen types I and III in developing human lung tissues from 12 to 40 weeks of gestation, and also in neonatal disorders such as respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). Lung tissues were obtained at autopsy from 60 non-malformed cases. All tissues were analysed by immunohistochemistry and 24 were also investigated by mRNA in situ hybridization. The precursor proteins and mRNA of both collagens were expressed in abundance in pulmonary arteries and veins during all developmental periods. In RDS and BPD, precursor proteins and mRNAs of both collagen types were increased within alveolar walls. The cells in these locations showed alpha-smooth muscle actin, vimentin, and variable desmin immunoreactivity. Collagen I and III precursor proteins and mRNA were also observed in pleura, bronchi, bronchioles, and around chondrocytes during all developmental periods and in diseased lung. In conclusion, collagens I and III were expressed in a similar way in and around various cell types in the developing lung and their expression was increased within alveolar walls in RDS and BPD. Myofibroblast-type cells appeared to produce mRNA for both types of collagen in alveoli.

Actins↗

PubMed2004

Differently cross-linked and uncross-linked carboxy-terminal telopeptides of type I collagen in human mineralised bone.

In bone matrix, type I collagen is stabilised by covalent cross-links formed between adjacent collagen molecules; the majority of which is believed to be immature, divalent bonds. For studying these immature forms in detail, we have developed an immunoassay for a synthetic peptide SP 4 that is analogous with and detects a linear epitope within the C-telopeptide of alpha1-chain of type I collagen. The SP 4 assay, together with the ICTP assay, which is specific for the trivalently cross-linked C-telopeptide, was used for the isolation of the differently cross-linked C-telopeptide structures of the alpha1-chain of type I collagen present in mineralised human bone. Amino acid analysis, peptide sequencing and MALDI-TOF mass spectrometry were used to identify and characterise each of the isolated structures. The cross-link content of each isolated peptide was identified. In the trivalent ICTP peptide, only 40% was cross-linked with pyridinoline, the remainder of the cross-links being currently uncharacterized. The divalent peptides contained only previously characterised cross-linking structures. Most of the divalent cross-links were dihydroxylysinonorleucine (DHLNL), with minor amounts of hydroxylysinonorleucine (HLNL). The relative proportion of the HLNL cross-link was slightly higher in the divalent alpha1Calpha2H peptide. A substantial amount of uncross-linked telopeptide structures was also found. Previous studies, where direct chemical cross-link analyses have been used to assess the maturity of cross-linking, have inferred that bone contains more divalently than trivalently cross-linked C-telopeptides. The immunochemical peptide approach used in this study may help to detect presently uncharacterized, trivalent cross-links, the presence of which is strongly suggested in this study. It also provides additional information regarding the extent and maturity of tissue type I collagen cross-linking in health and disease.

Adult↗

PubMed2004

Plasma B-type natriuretic peptide reflects left ventricular hypertrophy and diastolic function in hypertension.

BACKGROUND: Hypertension is associated with changes in concentrations of vasoactive peptides and procollagen propeptides, but their relationships with left ventricular hypertrophy and cardiac function are unclear. METHODS: We measured plasma levels of atrial natriuretic peptide (ANP), its amino terminal propeptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-1 (ET-1), and serum levels of the aminoterminal propeptide of type I procollagen (PINP) and the aminoterminal propeptide of type III procollagen (PIIINP) and echocardiographic parameters in 97 patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial. RESULTS: Median values (reference values) of the peptides were: ANP 11.2 (6.9-14.9) pmol/l, NT-proANP 351 (143-311) pmol/l, BNP 1.1 (0.4-7.2) pmol/l, ET-1 8.7 (1.2-5.0) pmol/l, PIIINP 2.8 (1.7-4.2) microg/l and PINP 29 (19-84) microg/l. Plasma BNP levels in patients with left ventricular hypertrophy (1.2 pmol/l) and patients with echocardiographic signs of diastolic dysfunction (1.5 pmol/l) were greater than those in patients without hypertrophy (0.7 pmol/l) and normal diastolic parameters (0.9 pmol/l) (p<0.05). BNP was the only biochemical parameter that independently predicted interventricular septal diastolic diameter (p<0.05), left ventricular mass index (p<0.01) and ratio of the velocity-time integrals of the E and A waves of the mitral inflow in a stepwise logistic regression analysis (p<0.05). CONCLUSIONS: The results show that BNP reflects the remodelling process in hypertension.

Adult↗

PubMed2004

Radiation-induced changes in skin type I and III collagen synthesis during and after conventionally fractionated radiotherapy.

BACKGROUND AND PURPOSE: To measure local changes of collagen metabolism in irradiated breast skin and systemic changes in serum during and after radiotherapy and correlate these changes with skin thickness, erythema and palpable subcutaneous induration. PATIENTS AND METHODS: Aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively) were measured from skin suction blister fluid (SBF) in 21 breast cancer patients with breast conserving surgery and conventionally fractionated radiotherapy (RT) to a total dose of 50Gy. Suction blisters were induced in the operated and contralateral breast skin before RT, at 2.5 weeks, at the end of RT, and at 1, 4, 7, 12 and 24 months post-treatment. Blood samples for serum were taken simultaneously with SBF induction. Skin thickness of the suction blister sites was measured with a high-frequency ultrasound device. The investigated sites were scored for erythema at the end of RT and palpable subcutaneous induration at 1 and 2 years post-treatment. RESULTS: In SBF the mean levels of PINP and PIIINP of the operated breast before RT were about 3-4 times higher than those in the contralateral breast due to the operation-related wound healing. The synthesis of PINP in irradiated breast after RT increased 7.7-fold (P < 0.001) 4 months post-irradiation. The PIIINP synthesis was at maximum at 1 month post-irradiation (P < 0.001). Both synthesis stayed elevated until 2 years. The level of PINP correlated significantly with the palpable skin induration at 1 and 2 years (P = 0.038 and P = 0.003, respectively). The skin thickness of the irradiated breast was highest at 4 months post-treatment and significantly elevated until 1 year. The skin thickness correlated with the PINP level until 7 months and with PIIINP between 4 and 18 months. The PINP/PIIINP ratio reached the maximum at 4 months and stayed elevated until 2 years. No change in mean serum level of PINP was found during or after RT. CONCLUSIONS: We demonstrated a maximum and elevated levels for PINP and PIIINP skin collagen metabolism determined from SBF during the 2 years' follow-up. Elevated levels of PINP and PIIINP correlated with the thickening of the skin and subcutaneous induration but not with erythema.

Adult↗

PubMed2004

Early degradation and serum appearance of type I collagen fragments after myocardial infarction.

Although extracellular matrix-degrading enzymes matrix metalloproteinases (MMPs) are activated within minutes after myocardial infarction (MI), the time course of early MI-induced type I cardiac collagen degradation has not been assessed, nor has the ability of MMP inhibitor compounds, such as doxycycline (DOX), to limit these events. The objective of this study was to assess serum biomarker evidence of myocardial type I collagen degradation early (<48 h) after coronary occlusion (CO) and determine the capacity of DOX to ameliorate its release. CO studies were performed in untreated and DOX pre-treated pigs. Treated animals received DOX at 30 mg/kg/d. Radioimmunoassays were performed for serum levels of C-terminal telopeptide of collagen type I (ICTP) fragments. ICTP groups peaked by 6 h after MI. However, in DOX-treated animals, ICTP values returned to normal by 8 h. Average serum concentrations for ICTP values from 0 to 48 h post-MI were significantly inhibited by DOX treatment. In conclusion, serum biomarker results indicate that type I collagen degradation occurs within minutes after MI and that DOX likely reduces its degradation.

Animals↗