Biomedical subjects

J Risteli

Publications and source records attributed to J Risteli.

At least 73 records · Page 4Linked to original sources

PubMed1999

The extracellular matrix in skin tumor development-a morphological study.

The development of cancer involves epithelial-stromal interactions. Alterations in the synthesis and deposition of type I and III collagens are related to the tumor morphology. Skin carcinogenesis in experimental animals provides a reliable model for the development of neoplasia. Ultraviolet (UV) irradiation is the main etiological factor for epidermal dysplasia and malignant tumors in man, but also for dermal degeneration. Non-neoplastic dermal changes and skin tumors induced by ultraviolet irradiation and 7,12-dimethylbenz(a)anthracene were investigated in various mouse strains with different susceptibilities to tumor formation. UVB irradiation resulted in an increased immunoreactivity of collagens in the dermis, in comparison with 7,12-dimethylbenz(a)anthracene. Increased synthesis and deposition of type I and III collagens were found in the stroma adjacent to benign alterations. In well-differentiated squamous cell carcinomas, a similar induction of collagen synthesis and deposition was observed. The destruction of fibrillary structures was more pronounced during the decrease of differentiation from moderately to poorly differentiated squamous cell carcinomas. Anaplastic carcinomas with spindle cell morphology displayed a delicate meshwork of reticular fibers and collagen III, and abnormal expression of mRNA for collagens in some malignant cells with epithelial characteristics. The underlying stroma reacts to the development of epithelial tumors in a reproducible way, which is related to the carcinogenic agent involved.

Animals↗

PubMed1999

The value of synovial fluid analysis in the assessment of knee joint destruction in arthritis in a three year follow up study.

OBJECTIVES: To assess the predictive significance of synovial fluid (SF) analysis for progressive radiological knee joint destruction in arthritis. METHODS: Altogether 55 patients with arthritis and knee joint effusion were included in the study. The diagnosis was rheumatoid arthritis (RA) for 44 of them, chronic seronegative spondylarthropathy for seven and juvenile rheumatoid arthritis for four. The mean age of the patients was 51.8 (SD 14.9, range 19-82) years, and the mean duration of disease 10.9 (SD 9.2, range 0.5-37) years. In addition to the routine laboratory tests, different markers of collagen synthesis and breakdown in serum and SF were assessed. The radiological grade of the knee joint was assessed by Larsen's method at the baseline and after a three year follow up. RESULTS: During the follow up, Larsen's grade deteriorated in 22 (40%) patients. These patients had a significantly higher median level of cross linked carboxyterminal telopeptide of type I collagen (ICTP) in SF at entry than those who had a stable index (p = 0.035). Serum ICTP did not have any predictive value for a specific joint. The median levels of total SF leucocytes (p = 0.012) and the subgroup of polymorphonuclear leucocytes (p = 0.018) were higher in the patients with a stable Larsen's index. However, the relation of SF leucocyte level to radiological progression could not be confirmed in the RA group. CONCLUSION: It is concluded that SF analysis may help in the identification of patients with inflammatory arthritis who are at risk for progressive destruction in a particular joint. A high total SF leucocyte level is not necessarily associated with a poor prognosis. Instead, a high SF ICTP level seems to reflect accelerated bone degradation.

Adult↗

PubMed1999

Complete processing of type III collagen in atherosclerotic plaques.

The extent of processing of type III collagen is assessed, and the proportions of type I and III collagens are estimated in atherosclerotic plaques obtained from the carotid artery, common femoral artery, and aorta. The fraction of type III collagen that had retained its amino-terminal propeptide (pN-collagen) was 42% in the soluble extract but only 0.0081% in the insoluble residue. Taken together, only 0.011% of the type III collagen in whole plaques was in the form of type III pN-collagen. Together with the small amounts of the free propeptides of type I procollagen, this finding indicates a low rate of collagen turnover. The amounts of solubilized telopeptides of type I and III collagens were measured, after heat denaturation and trypsin digestion of the collagenous helix, by specific immunoassays for the corresponding trypsin-generated antigens. The mean proportion of type III collagen was 61% (95% confidence interval, 58% to 65%) in the carotid and femoral artery plaques and 56% (95% confidence interval, 44% to 68%) in the aortic specimens. The completely processed and cross-linked type III collagen seems to be the major collagen type in atherosclerotic plaques.

Adult↗

PubMed1999

Type III and type I procollagen markers in fibrosing alveolitis.

Deposition of types I and III collagen is a typical feature in the development of pulmonary fibrosis. We assessed the propeptides of these procollagens as prognostic markers in 18 patients with fibrosing alveolitis. We analyzed the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) from samples of bronchoalveolar lavage fluid (BALF) and serum, and also estimated their concentrations in epithelial lining fluid (ELF) by the urea method. The level of PIIINP in serum (p < 0.05), BALF (p < 0.05), and ELF (p < 0.05), and the levels of PICP in BALF (p < 0.001) and ELF (p < 0.001) but not in serum, were significantly increased in the patients with fibrosing alveolitis as compared with 17 controls who had been investigated for minor respiratory symptoms. In the BALF and ELF of patients with fibrosing alveolitis, PICP but not PIIINP had significant negative correlations with the specific diffusion coefficient for carbon monoxide (DLCO/ VA). The amino-terminal propeptide of type III procollagen and the carboxy-terminal propeptide of type I procollagen in BALF correlated significantly with one another. During the follow-up period of 6 yr, seven of the 18 patients with fibrosing alveolitis died of the disease, 3 others died of malignancy, and one patient died from an unknown cause. DLCO (p < 0.05) differed significantly between the surviving patients and those who died of fibrosing alveolitis, and detectable PIIINP in BALF predicted death from fibrosing alveolitis (p = 0.05). In conclusion, these results show that PIIINP in BALF, ELF, and serum, and PICP in BALF and ELF, are increased in patients with fibrosing alveolitis. A high level of PICP in BALF, and especially in ELF, suggests a chronic process and increased synthesis of type I collagen in the lungs, whereas PIIINP in BALF and ELF suggests active disease and a poor prognosis.

Biomarkers↗

PubMed1999

Diurnal variation in concentrations of various markers of bone metabolism in dogs.

OBJECTIVE: To evaluate diurnal variation in concentrations of selected markers of bone metabolism in dogs. ANIMALS: Ten 3- to 4-year-old ovariectomized Beagles. PROCEDURE: Blood and urine samples were obtained in the morning before dogs were fed (8 AM) and then at 2-hour intervals for 24 hours. This procedure was repeated 2 weeks later. Concentrations of osteocalcin (OC) and carboxy terminal telopeptide of type-I collagen (ICTP) were measured in serum, using a radioimmunoassay; concentrations of hydroxyproline (HYP), pyridinoline (PYD), and deoxypyridinoline (DPD) were analyzed in urine. Hydroxyproline concentration was measured by means of a colorimetric test, whereas PYD and DPD concentrations were quantified by use of high-performance liquid chromatography. RESULTS: In both parts of the study, HYP concentrations increased significantly, compared with values before feeding, until 8 hours after feeding; HYP concentrations then returned to prefeeding values. Concentrations of DPD and PYD decreased from before feeding until 2 PM and then increased until 8 PM. The ICTP concentrations slowly decreased until 4 PM but returned to prefeeding values thereafter. In both parts of the study, concentrations of OC decreased during the day and then increased to reach values similar to those obtained before feeding. CONCLUSIONS: Changes in the concentrations of bone markers were detected throughout the day in the dogs of this study. Increase in HYP concentration most likely was related to feeding. As documented for bone resorption and formation in other species, circadian rhythms were evident for concentrations of DPD, PYD, and OC. Investigators should consider the time of sample collection when measuring these markers.

Alkaline Phosphatase↗

PubMed1999

Type I and III collagen metabolites as predictors of clinical outcome in epithelial ovarian cancer.

We evaluated the significance of biochemical tumor markers, ie, aminoterminal propeptide of type III procoliagen, trivalently cross-linked COOH-terminal telopeptide of type I collagen (ICTP), aminoterminal propeptide of type I procollagen, and CA 125 in the prediction of ovarian cancer outcome and compared them with several classical indicators of prognosis. The concentrations of biochemical markers were determined from the preoperative serum specimens of 55 patients with epithelial ovarian cancer. In the univariate analysis, all biochemical markers except PINP and all conventional prognostic indicators except histological subtype correlated significantly with survival. In the multivariate Cox analysis of biochemical markers, serum ICTP remained the only significant prognostic indicator of overall survival. Among all variables, clinical stage and ICTP were the only independent and significant determinants of prognosis. Because the content of trivalently cross-linked, mature type I collagen (the breakdown of which is detectable in the ICTP test) in malignant ovarian cancer tissue has been reported to be lower and that of bivalently cross-linked and non-cross-linked collagen has been reported to be higher than in benign tumors, the source of excess ICTP in the circulation of ovarian cancer patients is most likely the degradative damage of soft tissues surrounding the progressively growing malignant lesions. The serum ICTP concentration can thus be regarded as an indicator of the invasion of ovarian cancer. Such information is not available by conventional methods. Therefore, the ICTP test will improve the accuracy of predicting clinical outcome in this disease.

Adult↗

PubMed1998

Type I procollagen synthesis is regulated by steroids and related hormones in human osteosarcoma cells.

Change in the synthesis of type I collagen, the major extracellular matrix component of skin and bone, are associated with normal growth, tissue repair processes, and several pathological conditions. Expression of the COL 1A1 gene is regulated by transcriptional and post-transcriptional mechanisms. However, the hormonal regulation of type I collagen synthesis in human bone has not been well characterized. We have studied the influence of calcitriol, dexamethasone, retinoic acid, and estradiol on the COL 1A1 gene expression by determining the secretion of the C-terminal propeptide (PICP) and the levels of alpha 1(I) procollagen mRNA in cultured human MG-63 and SaOs-2 osteoblast-like osteosarcoma cells. Similar experiments were also performed with respect to expression of the nuclear proto-oncogenes, c-fos and c-jun, in MG-63 cells. In MG-63 cells, calcitriol stimulated the synthesis and secretion of PICP. The alpha 1(I) procollagen mRNA level was elevated with no effect on message stability, indicating a transcriptional mechanism of regulation. In contrast, dexamethasone treatment was accompanied by an accelerated rate of alpha 1(I) procollagen mRNA turnover, observed as decreased amounts of the message and the secreted PICP, implying a posttranscriptional regulation. Retinoic acid, in turn, decreased the levels of alpha 1(I) procollagen mRNA and secreted PICP by slowing down transcription of the COL1A1 gene without any effect on message stability. The ability of these hormones to regulate the alpha 1(I) transcripts was sensitive to puromycin treatment, suggesting an involvement of an induced mediator protein in the action of the hormones on the COL1A1 gene. Both dexamethasone and calcitriol rapidly but transiently increased the expression of the c-fos and c-jun proto-oncogenes. Neither proto-oncogene responded to retinoic acid treatment with significant changes in mRNA levels. Estradiol treatment was found to have no influence on type I procollagen synthesis. In SaOs-2 cells, which are not as well differentiated as the MG-63 cells, calcitriol and dexamethasone did not influence type I procollagen synthesis. Retinoic acid as well as estradiol reduced collagen gene expression in these cells. These findings suggest that hormonal effects on type I procollagen synthesis may depend on the maturational state of the osteoblastic cells that express different regulatory factors and receptors, resulting in, in each case, a finely adjusted rate of gene expression.

Administration, Topical↗

PubMed1998

Aberrant type I and type III collagen gene expression in human breast cancer in vivo.

Increased synthesis and degradation of extracellular matrix components are associated with breast cancer development. This study evaluated type I and type III procollagen mRNA expression and the corresponding protein synthesis and maturation, as well as the tissue distribution of these collagens, in benign breast lesions, infiltrating ductal carcinomas, and their metastases by in situ hybridization and immunohistochemistry. In the benign lesions, the type I and type III collagen bundles were regularly organized and the expression of the corresponding mRNA was weak, indicating a relatively slow collagen turnover. In the malignant tumours, increased expression of type I and type III procollagen mRNAs was observed in the fibroblastic cells of the stroma; the malignant epithelial cells did not participate. The staining of corresponding newly-synthesized pN-collagens showed aberrant bundles in the invasive front of the malignant tumours. Newly-synthesized type I and type III procollagens were occasionally observed in fibroblastic cells, particularly in grade 2 and grade 3 tumours. Metastases of breast carcinoma resembled poorly differentiated primary tumours with respect to their collagen synthesis and deposition. The increased synthesis of fibrillar type I and type III procollagens may serve as a pathway for tumour invasion. The enhanced synthesis is associated with the formation of aberrant collagen bundles, which may be more readily degradable and may thus facilitate breast tumour invasion.

Biomarkers, Tumor↗

PubMed1998

Collagen metabolism and growth in prepubertal children with asthma treated with inhaled steroids.

OBJECTIVE: To investigate growth and markers of collagen and bone metabolism in prepubertal children with asthma. STUDY DESIGN: We measured growth velocity over 12 months and markers of collagen types I and III synthesis (PINP, PICP, PIIINP), collagen type I degradation (ICTP), and bone metabolism (bone-specific alkaline phosphatase and osteocalcin) on one occasion in 56 prepubertal children with stable asthma, 39 of whom were treated with inhaled budesonide or beclomethasone. Collagen data were compared with normal control values. RESULTS: Children treated with inhaled steroids had reduced collagen synthesis (PINP, PIIINP) compared with control subjects (p = 0.038, p = 0.045), although PICP was increased (p = 0.05). Carboxyterminal telopeptide of type I collagen was reduced in patients treated with inhaled steroids (p < 0.0005) compared with nonsteroid-treated patients. Serum osteocalcin but not bone-specific alkaline phosphatase was significantly reduced in children treated with inhaled steroids (p < 0.02). Significant correlation was observed between PIIINP and ICTP and growth velocity. CONCLUSION: Collagen turnover is reduced in children with asthma receiving long-term inhaled steroid treatment. Markers of collagen synthesis provide a more accurate reflection of growth disturbance than osteocalcin and bone-specific alkaline phosphatase.

Administration, Inhalation↗

PubMed1998

Synthesis and breakdown of fibrillar collagens: concomitant phenomena in ovarian cancer.

The synthesis and degradation of type I and type III interstitial collagens releases several antigenic metabolites, whose measurement allows the metabolism of connective tissue to be evaluated under a variety of different conditions. In this study we investigated the influence of benign and malignant ovarian neoplasms on the metabolism of these collagens. The study population comprised patients with benign (n = 53), borderline (n = 6) or malignant (n = 36) ovarian neoplasms. We quantified the serum, cyst fluid and peritoneal/ascitic fluid concentrations of the amino-terminal propeptide of type I (PINP) and III (PIIINP) procollagens, indicators of the synthesis of type I and III collagen, respectively and the cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), an indicator of type I collagen degradation. Macrophage colony-stimulating factor 1 (CSF-1) concentration was also assayed as its serum level is increased in ovarian cancer and CSF-1 may be involved in the regulation of collagen metabolism. The concentration of each antigen was significantly higher in patients with malignant tumour than with benign neoplasm in each comparison, except for ICTP in peritoneal fluid and for CSF-1 in cyst fluid. The high ascitic fluid concentration of PINP, PIIINP or CSF-1 correlated with malignancy, and the low cyst fluid concentration of any of the four markers was indicative of benign tumour. Levels of CSF-1 did not correlate with the levels of any of the markers of collagen turnover. The concentration of PINP in ascites was about 50 times higher and in cyst fluid about eight times higher than that in the serum from patients with malignant tumour, whereas the respective ratios for ICTP were only 2.5 and 1.3. In such patients, the ratio of ascitic fluid to serum concentration was also about 80-fold higher for PIIINP and about 20-fold higher for PINP than for ICTP. The different distributions of PIIINP, PINP and ICTP suggests dominance of synthetic processes or retarded elimination of PIIINP and PINP in ovarian cancer. In advanced malignancies, the accumulation of PINP and PIIINP in abdominal space, possibly due to increased synthesis and/or failed resorption, may promote ascites formation. This study shows that both accelerated synthesis and breakdown of fibrillar collagens are characteristic of ovarian malignancy, and suggests that measurements of cyst fluid or ascitic fluid concentrations of collagen metabolites or CSF-1 could be used in the differential diagnosis of benign and malignant ovarian neoplasms.

Adult↗

PubMed1998

Demonstration of increased collagen synthesis in irradiated human skin in vivo.

Fibrosis is a common side-effect of radiation therapy. As a complex network of cytokines and other mediators plays a central role in the process leading to fibrosis, we used an in vivo method to measure skin collagen synthesis, taking into account the physiological conditions. We determined suction blister (i.e. interstitial) fluid concentrations of types I and III procollagen propeptides, reflecting types I and III collagen synthesis, in irradiated and unirradiated skin of breast cancer patients 1-5 years after surgery and radiation therapy, hence using the patients as their own controls. The mean concentrations of the measured collagen markers were approximately two times higher in the irradiated skin than in the unirradiated contralateral breast skin. The difference slowly diminishes with time. These results indicate that abundant collagen synthesis in the irradiated skin continues several years after discontinuation of the radiation therapy, leading to fibrosis. The method outlined here offers a new in vivo perspective to study events leading to radiation fibrosis.

Aged↗

PubMed1998

Aminoterminal propeptide of type I procollagen (PINP) correlates to bone loss and predicts the efficacy of antiresorptive therapy in pre- and post-menopausal non-metastatic breast cancer patients.

The aim of this study was to determine the correlation between changes in collagen metabolites (ICTP, mature cross-linked carboxy-terminal telopeptide of type I collagen; PINP, the amino-terminal propeptide of type I procollagen) and bone mineral density (BMD) in 206 pre- and post-menopausal breast cancer patients with non-metastatic disease. All patients received adjuvant cancer treatment--premenopausal patients chemotherapy and post-menopausal patients anti-oestrogens. In addition, the patients were also randomized to receive oral clodronate 1600 mg daily for 3 years. BMD was measured at baseline and at 1 and 2 years, the collagen metabolites at baseline and at 1 year. There was a highly significant negative correlation between the changes in PINP and BMD in lumbar spine and femoral neck from baseline to 12 months in all patients (r(s) = -0.68, P < 0.0001, and -0.45, P < 0.0001, respectively), and in pre- and post-menopausal patients separately. The changes in PINP levels at 12 months predict further changes in BMD at 24 months (r = -0.70, P < 0.0001, and -0.51, P < 0.0001, respectively). ICTP and BMD changes correlated significantly only in lumbar spine of premenopausal patients who developed rapid bone loss due to chemotherapy-induced amenorrhoea (r(s) = -0.34, P = 0.0003). The PINP levels at 12 months were significantly lower in the clodronate group than in the control group (P < 0.0001). Our results indicate that PINP is a sensitive marker of bone turnover rate. Changes in PINP levels significantly predicted changes in BMD and correlated with the antiresorptive efficacy of clodronate treatment.

Bone Density↗

PubMed1998

Circulating type I collagen degradation products: a new serum marker for clinical severity in patients with scleroderma?

Systemic sclerosis (SSc; scleroderma) results in the excessive deposition of extracellular matrix components in affected organs. This is partly due to enhanced synthesis; however, the role of degradative processes in this disease is still poorly understood. Sera of 32 patients with SSc (22 with the diffuse, 10 with the limited form) and of six patients with morphoea were assessed using radioimmunoassays for the cross-linked carboxy terminal telopeptide of type I collagen (ICTP) and for the amino terminal propeptide of type I procollagen (PINP) reflecting type I collagen degradation and synthesis, respectively. In 27 of the 32 patients with SSc, the concentration of ICTP was above the upper limit of the normal value (4.6 micrograms/L) and the mean level was clearly elevated at 7.92 micrograms/L. The ICTP concentration correlated with the skin score measuring the extent of the lesions, whereas no such correlation was found for PINP. The ICTP antigen in serum, studied by immunoblotting, had a molecular weight of about twice that of the trypsin-generated fragment isolated from human bone collagen. The mean concentration of serum PINP was 43.9 micrograms/L and no patient exceeded the upper limit of the normal range (80 micrograms/L). We report here for the first time that the concentration of the type I collagen degradation product ICTP in serum shows a close correlation with the extent of skin fibrosis in patients with SSc. We conclude that the increased deposition of type I collagen in this disease is accompanied by an increased turnover of this molecule, indicating a more complex derangement of synthetic and degradative processes than previously acknowledged.

Adult↗

PubMed1998

Type I and type III procollagen propeptides in amniotic fluid of normal pregnancies and in a case of mild osteogenesis imperfecta.

BACKGROUND: The propeptides derived from type I and III procollagens, PICP, PINP and PIIINP, indicate the synthesis of the corresponding collagens. Their circulating concentrations reflect the growth velocity in infants and children METHODS: We measured these propeptides in 145 samples of amniotic fluid of normal pregnancy. In addition, we have analysed an amniotic fluid and serum sample from a mother with osteogenesis imperfecta, and later the infant's serum sample was also collected for procollagen propeptide analysis. RESULTS: High concentrations of propeptides, 100-1000 times higher than those in adult serum, were found in early second trimester, decreasing significantly towards term, reflecting the decreased foetal growth rate. Interestingly, the amino-terminal propeptide of type I procollagen, PINP, decreased more that the corresponding carboxy-terminal propeptide, PICP, although both are in principle derived from the same protein. At both stages of pregnancy, the discrepant ratio of PICP to PINP indicated a molar excess of PINP. Abnormally low concentrations of PICP and PINP with normal PIIINP concentrations measured in amniotic fluid and in the serum indicated decreased synthesis of type I procollagen in a foetus/infant with mild osteogenesis imperfecta. CONCLUSIONS: Our data show a decrease in collagen synthesis with the stage of pregnancy and lower values of type I procollagen propeptides in a case of OI.

Adult↗

PubMed1998

Low incidence of osteoporosis in a two year follow-up of early community based patients with rheumatoid arthritis.

52 patients with early rheumatoid arthritis (RA) were followed with regular measurements of bone mineral density (BMD) and serum markers of type I collagen metabolism in order to determine whether they develop osteoporosis during the first two years of the disease course and if the changes in type I collagen metabolites reflect the alterations in BMD. The mean percentage BMD change over the first year of follow-up was -0.91 for lumbar spine (LS) and -0.76 for femoral neck (FN); the corresponding figures from 0 to 24 months was -1.3 and -0.8, respectively. During the follow-up, only five patients developed osteoporosis by the Z-score definition (<-1). If defined by T-score (<-2.5) none of the patients developed osteoporosis. The BMD change correlated neither with the clinical parameters of disease activity nor with the markers of collagen metabolism. However, the BMD change in FN was associated with the cumulative corticosteroid dose (r=-0.31, p <0.05, 95% CI -0.54 to -0.04). Reasons for the lack of accelerated bone loss in our series are open to various interpretations. This series was community based and most of the patients had mild RA. The patients were also actively treated and their physical function did not deteriorate.

Adult↗

PubMed1998

New lethal disease involving type I and III collagen defect resembling geroderma osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV.

We describe the clinical findings and biochemical features of a male child suffering from a so far undescribed lethal connective tissue disorder characterised by extreme hypermobility of the joints, lax skin, cataracts, severe growth retardation, and insufficient production of type I and type III procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy syndrome, and geroderma osteodysplastica, as these disorders show some symptoms and signs shared with our patient. The child died because of failure of the connective tissue structures joining the skull and the spine, leading to progressive spinal stenosis. The aortic valve was translucent and insufficient. The clinical symptoms and signs, together with histological findings, suggested a collagen defect. Studies on both skin fibroblast cultures and the patient's serum showed reduced synthesis of collagen types I and III at the protein and RNA levels. The sizes of the mRNAs and newly synthesised proteins were normal, excluding gross structural abnormalities. These findings are not in accordance with any other collagen defect characterised so far.

Adult↗

PubMed1998

Effects of long-term inhaled corticosteroids on skin collagen synthesis and thickness in asthmatic patients.

There are only a few studies on the adverse effects of inhaled corticosteroids on the skin in asthmatic patients. Therefore, we evaluated the effect of inhaled corticosteroids on de novo collagen synthesis of skin and bone, skin thickness and the total amount of skin collagen. Twenty seven consecutive new asthmatic patients, on a moderate dose of budesonide or beclomethasone dipropionate, were invited to take part in this prospective study. Radioimmunological analyses of aminoterminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) in suction blister fluid (SBF) of skin and in serum and carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carbox terminal telopeptide of type I collagen (ICTP) in serum were performed at entry and after 3 and 6 months of inhaled corticosteroid treatment. Ultrasound measurements of skin thickness at two sites were performed at entry, at 3 and 6 months and after 1-2 yrs of inhaled corticosteroid treatment in 20 patients, six of whom had been prescribed one or more courses of oral corticosteroids. Skin hydroxyproline of punch biopsies was determined to measure the total amount of skin collagen (males, at entry and at 6 months). Skin thickness and the total amount of skin collagen on the abdomen were unchanged after 1-2 yrs of inhaled corticosteroid use. A slight decrease was observed in the upper arm skin thickness, especially in those subjects who had received inhaled plus oral corticosteroids. The procollagen propeptide concentrations (PINP, PIIINP) were markedly decreased in SBF at 3 months and remained at this level at 6 months. In serum, a slight decrease was seen in the PINP, PIIINP and ICTP concentrations at 3 and 6 months. In conclusion, inhaled corticosteroids decrease the collagen synthesis of skin and bone, but skin thickness and the total amount of collagen in skin are not changed markedly after 1-2 yrs of treatment.

Administration, Inhalation↗

PubMed1998

Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy.

OBJECTIVE: To study whether levothyroxine (LT4) suppressive therapy exposes patients with differentiated thyroid cancer (TC) to an increased risk of osteoporosis. DESIGN AND METHODS: Markers of bone formation (serum alkaline phosphatase (ALP), osteocalcin (OC), type I procollagen carboxyterminal (PICP) and aminoterminal (PINP) propeptide) and resorption (serum type I collagen carboxyterminal telopeptide (ICTP) and urine hydroxyproline (HOP)), as well as serum intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25(OH)2-D) were measured in 29 patients (25 women, 4 men) with a median age of 45 years, and in 38 age- and sex-matched controls. In a subgroup of 14 patients the measurements were repeated after 5 weeks' interruption of LT4 therapy. Since the primary treatment of TC the patients had used TSH suppressive doses of LT4 (a mean daily dose of 215 microg) for 9 to 11 years. The bone mineral density (BMD) of patients and controls was measured by dual energy X-ray absorptiometry. RESULTS: When on T4 therapy, patients had significantly higher mean levels of ALP (+21%, P < 0.05), OC (+35%, P < 0.01), PICP (+10%, P < 0.05), PINP (+46%, P < 0.001), ICTP (+21%, P < 0.05), and HOP (+37%, P < 0.001) compared with controls. After stopping treatment, OC (-42%, P < 0.001), PINP (-7%, P < 0.05), and ICTP (-54%, P < 0.001) decreased, whereas PICP (+24%, P < 0.001) and 1,25(OH)2D (+29%, P < 0.01) increased. BMD of the lumbar spine and the upper femur was similar in patients and controls. CONCLUSIONS: Patients with differentiated TC have high bone turnover when on LT4 suppressive therapy, After withdrawing treatment both bone formation and resorption decrease acutely. During development of hypothyroidism, serum PICP and PINP, which form from the same type I procollagen molecule and should change similarly, behaved differently. This may be due to different effects of hypothyroidism on their removal through separate receptors in the liver.

Adult↗