RESUMO
BACKGROUND: As a component of the thyroid hormones (THs), iodine is vital for normal neurodevelopment during early life. However, both deficient and excess iodine may affect TH production, and data on iodine status in young children are scarce. OBJECTIVES: To describe iodine nutrition (iodine status and intake) in children ≤2 y of age in Innlandet County (Norway) and to describe the associations with maternal iodine nutrition. METHODS: A cross-sectional study was performed in a representative sample of mother-child pairs selected from 30 municipalities from November 2020 until October 2021. Iodine status [child urinary iodine concentration (UIC), maternal UIC, and breast milk iodine concentration (BMIC)] was measured. Child's iodine intake was estimated using 2 24-h dietary recalls (24-HR) and a food frequency questionnaire. The Multiple Source Method was used to estimate the usual iodine intake distributions from the 24-HR assessments. RESULTS: The median UIC in 333 children was 145 µg/L, indicating adequate iodine status according to the WHO cutoff (100 µg/L). The median usual iodine intake was 83 µg/d. Furthermore, 35% had suboptimal usual iodine intakes [below the proposed Estimated average requirement (72 µg/d)], whereas <1% had excessive usual iodine intakes [above the Upper intake level (200 µg/d)]. There was a positive correlation between children's iodine intake and BMIC (Spearman rank correlation coefficient r = 0.67, P < 0.001), and between children's UIC and BMIC (r = 0.43, P < 0.001), maternal UIC (r = 0.23, P = 0.001), and maternal iodine intake (r = 0.20, P = 0.004). CONCLUSION: Despite a median UIC above the cutoff for iodine sufficiency, more than a third of the children had suboptimal usual iodine intakes. Our findings suggest that many children will benefit from iodine fortification and that risk of iodine excess in this age group is low.
Assuntos
Iodo , Feminino , Humanos , Pré-Escolar , Estudos Transversais , Estado Nutricional , Leite Humano/química , NoruegaRESUMO
BACKGROUND: Obstetric anal sphincter injury (OASI) is a common and severe complication of vaginal delivery and may have short- and long-term consequences, including anal incontinence, sexual dysfunction and reduced quality of life. The rate of OASI varies substantially between studies and national birth statistics, and a recent meta-analysis concluded that there is a need to identify unrecognized risk factors. Our aim was therefore to explore both potential modifiable and non-modifiable risk factors for OASI. METHODS: We performed a case-control study in a single center maternity clinic in South-Eastern Norway. Data were extracted retrospectively from an institutional birth registry. The main outcome measure was the occurrence of the woman's first-time 3rd or 4th degree perineal lesion (OASI) following singleton vaginal birth after 30 weeks' gestation. For each woman with OASI the first subsequent vaginal singleton delivery matched for parity was elected as control. The study population included 421 women with OASI and 421 matched controls who gave birth during 1990-2002. Potential risk factors for OASI were assessed by conditional logistic regression analyses. RESULTS: The mean incidence of OASI was 3.4% of vaginal deliveries, but it increased from 1.9% to 5.8% during the study period. In the final multivariate regression model, higher maternal age and birthweight for primiparous women, and higher birthweight for the multiparous women, were the only non-modifiable variables associated with OASI. Amniotomy was the strongest modifiable risk factor for OASI in both primi- (odds ratio [OR] 4.84; 95% confidence interval [CI] 2.60-9.02) and multiparous (OR 3.76; 95% CI 1.45-9.76) women, followed by augmentation with oxytocin (primiparous: OR 1.63; 95% CI 1.08-2.46, multiparous: OR 3.70; 95% CI 1.79-7.67). Vacuum extraction and forceps delivery were only significant risk factors in primiparous women (vacuum: OR 1.91; 95% CI 1.03-3.57, forceps: OR 2.37; 95% CI 1.14-4.92), and episiotomy in multiparous women (OR 2.64; 95% CI 1.36-5.14). CONCLUSIONS: Amniotomy may be an unrecognized independent modifiable risk factor for OASI and should be further investigated for its potential role in preventive strategies.
Assuntos
Canal Anal , Complicações do Trabalho de Parto , Canal Anal/lesões , Estudos de Casos e Controles , Feminino , Humanos , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/etiologia , Complicações do Trabalho de Parto/prevenção & controle , Gravidez , Qualidade de Vida , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Adolescents are recommended to get 8-10 h of sleep at night, yet more than 80% fail to obtain this goal. Energy drink (ED) consumption has been linked to later bedtime in adolescents. Therefore, we aimed to investigate the potential association between ED consumption and sleep duration, and shuteye latency among adolescents in Norway. METHODS: This study was based on data from 15- to 16-year-old adolescents living in Oppland County in 2017. In total, 1353 adolescents were included in the analysis. Multiple regression models were used to estimate the associations between the frequency of ED consumption with sleep duration, shuteye latency, and getting 8 h of sleep. RESULTS: Forty-six point five percent of the adolescents reported sleeping more than 8 h at night. Those who reported ED consumption at any frequency had significantly shorter sleep duration than those who did not. On average, high consumers of ED (consuming ED ≥ 4 times a week) had 0.95 (95% CI: 0.61, 1.28) hours (i.e., 57 min) less sleep than those who never consumed ED. In addition, high consumers had more than 25 min (95% CI: 13.95, 36.92) longer shuteye period than those who never consumed ED. CONCLUSION: Most ED consumers fail to obtain the recommended 8 h of sleep at night, which could be a consequence of shorter sleep duration and longer shuteye latency. We found a dose-response relationship between frequency of ED consumption and reduced sleep. Yet, the potential long-term effects of both ED consumption and insufficient sleep among adolescents remain unclear.
Assuntos
Bebidas Energéticas , Transtornos do Sono-Vigília , Adolescente , Estudos Transversais , Humanos , Sono/fisiologia , Fatores de TempoRESUMO
AIM: The aim was to examine if breastfeeding practices were associated with body mass index (BMI) and risk of overweight or obesity in third grade (8 years) of elementary school. METHODS: In a regional cohort, we related BMI z-scores and presence of overweight or obesity at 8 years of age with ever being breastfed and with duration of exclusive and partial breastfeeding after adjusting for potential confounders. Parents completed questionnaires on breastfeeding and sociodemographic and lifestyle factors at school entry, and public health nurses measured height and weight. For non-participants, the nurses anonymously reported these measurements together with sex and age. RESULTS: 90% of participants had been breastfed. In adjusted analyses, BMI z-scores were not significantly related to whether or not the child had been breastfed (P = .64), or to the duration of exclusive (P = .80) or partial breastfeeding (P = .94). Logistic regression also showed no significant association between breastfeeding measures and overweight or obesity. CONCLUSION: This study on 8-year-old Norwegian children did not support a commonly held notion that breastfeeding reduces the risk of overweight or obesity.
Assuntos
Aleitamento Materno/estatística & dados numéricos , Obesidade Infantil/epidemiologia , Criança , Feminino , Humanos , Masculino , Noruega/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The prevalence of overweight and obesity (OWOB) has stabilized in some countries, but a portion of children with high body mass index (BMI) may have become heavier. This study aimed to describe the distributions of BMI and the point prevalence of OWOB in Norwegian adolescents in 2002 and 2017. METHODS: A cross-sectional study involving 15- to 16-year-old adolescents in Oppland, Norway, was undertaken in 2002 and 2017. We calculated their BMI, BMI z-scores (BMIz), and the prevalence of OWOB. RESULTS: The mean BMI increased from 20.7 to 21.4 (p < 0.001) for girls but remained unchanged at 21.5 vs 21.4 (p = 0.80) for boys. The prevalence of OWOB increased from 9 to 14% among girls (difference 5, 95% CI: 2, 8) and from 17 to 20% among boys (difference 3, 95% CI: - 1, 6%). The BMI density plots revealed similar shapes at both time points for both sexes, but the distribution for girls shifted to the right from 2002 to 2017. CONCLUSION: Contrary to previous knowledge, we found that the increase in OWOB presented a uniform shift in the entire BMI distribution for 15-16-year-old Norwegian girls and was not due to a larger shift in a specific subpopulation in the upper percentiles.
Assuntos
Índice de Massa Corporal , Sobrepeso/epidemiologia , Adolescente , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Noruega/epidemiologia , Obesidade Infantil/epidemiologia , Prevalência , Caracteres Sexuais , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Hidden behind subtle symptoms and unspecific signs, heart failure in children can pose a significant challenge regarding diagnostic approach as well as treatment strategy. A case report is presented for an 11-month-year-old girl with recurrent airway infections and signs of cardiac failure as a consequence of ventricular non-compaction. This disease is morphologically distinct; most likely a developmental defect of the ventricular myocardium. It is characterized by heterogeneity regarding both heredity, age of presentation, symptoms, hemodynamic disturbances, prognosis and therapeutic approach. In general, a symptomatic child with non-compaction has a poor prognosis with a prospect of severe cardiac failure and death. The article summarises how to approach a child presenting with cardiac failure; i.e. initial evaluation, diagnostic and initial stabilizing procedures and alternative treatment strategies. We also discuss specific treatment of ventricular non-compaction and briefly report on children with non-compaction at the largest pediatric cardiology centre in Norway.
Assuntos
Insuficiência Cardíaca/diagnóstico , Infecções Respiratórias/diagnóstico , Cateterismo Cardíaco , Diagnóstico Diferencial , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Lactente , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Recidiva , UltrassonografiaRESUMO
Recommendations for sufficient vitamin D intake in children were recently revised in Norway. However, optimal levels of vitamin D are still debated and knowledge on supplementation and vitamin D levels in healthy children in Norway is scarce. Therefore, we measured the plasma-concentration of 25-hydroxyvitamin D (25(OH)D) in children and adolescents attending the outpatient paediatric clinics in Innlandet Hospital Trust, Norway during two consecutive years (2015-2017). We recruited 301 children and adolescents aged 5 months to 18 years (mean 7.8, SD 4.4 years) for the study and obtained sample material for 25(OH)D measurements from 295 (98%). Information on diet, vitamin D supplementation, sun exposure, ethnicity, parental education and general health was collected by questionnaire. 25(OH)D levels were analysed and determinants for 25(OH)D were estimated by linear regression. 1.0% of the children had deficient levels (25(OH)D < 25 nmol/L) and 21.0% had insufficient levels (25-50 nmol/L). 25(OH)D levels ranging from 50 to 75 nmol/L were found among 38.3%, while 39.7% had levels above 75 nmol/L. The mean 25(OH)D level was 70.0 nmol/L (SD 23.4, range 17-142 nmol/L) with a significant seasonal variation with lowest levels in mid-winter and highest in late summer. In addition to seasonal variation independent determinants for 25(OH)D-levels were age of the child, parental ethnicity, vitamin D supplementation and soda consumption. Along with parental ethnicity other than Nordic, age was the strongest determinant of 25(OH)D, with adolescents having the lowest levels.
Assuntos
Dieta/efeitos adversos , Estado Nutricional , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Adolescente , Fatores Etários , Criança , Pré-Escolar , Dieta/etnologia , Suplementos Nutricionais/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Noruega/epidemiologia , Noruega/etnologia , Estações do Ano , Luz Solar , Vitamina D/sangue , Deficiência de Vitamina D/etnologiaRESUMO
The aim of this study was to explore the association between adolescent subjective social status (SSS) and body mass index (BMI) at two different time points and to determine whether this association was mediated by health-related behaviors. In 2002 (n = 1596) and 2017 (n = 1534), tenth-grade students (15-16 years old) in schools in the District of Oppland, Norway, completed a survey. Four categories of perceived family economy were measured as SSS, and structural equation modeling was performed, including a latent variable for unhealthy behavior derived from cigarette smoking, snuff-use, and alcohol-drinking as well as dietary and exercise as mediators. No linear association was found between SSS and BMI in 2002 (standardized ß -0.02, (95% confidence interval (CI) -0.07, 0.03)). However, an association was present in 2017 (standardized ß -0.05 (95% CI -0.10, -0.001)), indicating that BMI decreased by 0.05 standard deviations (0.05 × 3.1 = 0.16 BMI unit) for every one-category increase in SSS. This association was mediated by exercise (standardized ß -0.013 (95% CI -0.02, -0.004) and unhealthy behavior (standardized ß -0.009 (95% CI -0.002, -0.04)). In conclusion, a direct association between SSS and BMI was found in 2017 in this repeated cross-sectional survey of 15-16-year-old Norwegian adolescents. This association was mediated through health-related behavior.
Assuntos
Comportamento do Adolescente , Índice de Massa Corporal , Comportamentos Relacionados com a Saúde , Classe Social , Adolescente , Estudos Transversais , Humanos , Noruega/epidemiologia , Instituições Acadêmicas , Fatores SocioeconômicosRESUMO
PURPOSE: Only about 50% of metastatic breast cancer patients benefit from cytotoxic chemotherapy. Today, no validated markers exist for prediction of chemotherapy sensitivity/resistance in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against apoptosis, and the purpose of the present study was to test the hypothesis that tumors expressing high levels of TIMP-1 are protected against apoptosis-inducing agents and thus less sensitive to apoptosis-inducing chemotherapeutic drugs. EXPERIMENTAL DESIGN: We investigated the association between primary tumor expression levels of TIMP-1 protein and objective response to first-line chemotherapy in 173 patients with metastatic breast cancer. RESULTS: When analyzed as a continuous log-transformed variable, increasing TIMP-1 levels were significantly associated with lack of response to cyclophosphamide/methotrexate/5-fluorouracil and anthracycline-based chemotherapy (P = 0.01; odds ratio, 2.0; 95% confidence interval, 1.1-3.3). In a multivariate model, including lymph node status, steroid hormone receptor status, menopausal status, dominant metastases site, type of chemotherapy, and disease-free interval, TIMP-1 was significantly associated with resistance to treatment (P = 0.03; odds ratio, 1.7; 95% confidence interval, 1.1-3.3). CONCLUSIONS: In the present exploratory study, we showed that elevated tumor tissue TIMP-1 levels were significantly associated with a poor response to chemotherapy. By using TIMP-1, we identified a group of patients with metastatic breast cancer, which hardly respond to the most frequently used chemotherapy regimes (i.e., cyclophosphamide/methotrexate/5-fluorouracil and anthracyclines).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Adulto , Idoso , Antraciclinas/farmacologia , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/diagnóstico , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
PURPOSE: In the present study, we investigated the association between tumor tissue levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and prognosis in patients with primary breast cancer and analyzed whether TIMP-1 may be useful as a prognostic marker in combination with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1). EXPERIMENTAL DESIGN: In cytosolic extracts of 2984 primary breast tumors, total levels of TIMP-1 were determined using an established, validated ELISA. Levels of uPA and PAI-1 have previously been determined in the extracts. RESULTS: Univariate survival analysis showed a significant relationship between higher levels of TIMP-1 (continuous log-transformed variable) and poor prognosis [recurrence-free survival (RFS), overall survival (OS); P < 0.001]. Performing isotonic regression analysis, we identified a cut point to classify tumors as TIMP-1-low or TIMP-1-high. Using this cut point, high levels of TIMP-1 were significantly associated with shorter survival in univariate analysis, both in the total patient group (RFS, OS; P < 0.001), in the node-negative subgroup (RFS, hazard ratio = 1.28, P = 0.006), and in the node-positive subgroup (RFS, hazard ratio = 1.43, P < 0.001). In multivariate analysis, including uPA and PAI-1, TIMP-1 was significantly associated with shorter RFS, both when included as a continuous log-transformed (P = 0.03) and as a dichotomized variable (P = 0.002). CONCLUSIONS: This study validates previous findings that tumor tissue levels of TIMP-1 are associated with prognosis in patients with primary breast cancer. It confirms that TIMP-1 may be useful as a prognostic marker in combination with uPA/PAI-1 and adds substantial positive information on the use of TIMP-1 as a prognostic marker in breast cancer.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Citosol/metabolismo , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/metabolismo , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores de TempoRESUMO
PURPOSE: The purpose of this study was to measure total levels of tissue inhibitor of metalloproteinases (TIMP-1) by ELISA in plasma from blood donors, patients with inflammatory bowel disease (IBD), and patients with cancer and to correlate the results to patient diagnosis. EXPERIMENTAL DESIGN: Total TIMP-1 plasma levels were measured by ELISA in blood samples from two different blood donor populations from IBD patients, and preoperative samples from patients with primary colon cancer (CC), rectal cancer (RC), or breast cancer. RESULTS: There were no significant differences in plasma TIMP-1 levels between healthy donors and IBD or breast cancer patients, whereas patients with CC or RC had significantly elevated TIMP-1 levels. Total TIMP-1 levels identified patients with CC with a sensitivity of 63% at 98% specificity, patients with early CC (Dukes' A+B) with a sensitivity of 56% at 98% specificity, and patients with right-sided CC with a sensitivity of 72% at 98% specificity. Combining carcinoembryonic antigen and TIMP-1 measurements increased the sensitivities obtained from TIMP-1 measurements alone. CONCLUSIONS: TIMP-1 was significantly elevated in plasma from CC and RC patients, including those with early-stage disease. Sensitivity and specificity were both sufficiently high to consider TIMP-1 as a marker for the early identification of CC patients, in particular, those with right-sided CC.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias do Colo/enzimologia , Neoplasias Retais/enzimologia , Inibidor Tecidual de Metaloproteinase-1/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doadores de Sangue , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Neoplasias do Colo/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/enzimologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Colorectal cancer patients have increased plasma levels of tissue inhibitor of metalloproteinases-1 (TIMP-1). However, it remains unresolved whether colorectal adenomas are associated with increased plasma TIMP-1. Plasma TIMP-1 levels were determined using an immunoassay in 121 patients prospectively enrolled from surveillance colonoscopy programmes. TIMP-1 levels were correlated to various clinicopathological parameters. No significant associations were found between plasma TIMP-1 and size, macro- or microscopic morphology or grade of dysplasia of the adenomas. No significant differences in TIMP-1 levels were found between patients with adenomas (n = 36), hyperplastic polyps (n = 12) or no pathology (n = 68) of the large intestine. However, patients with colonic (n = 3) or rectal (n = 2) adenocarcinomas had significantly increased TIMP-1 levels (P = 0.02). The present study demonstrates that measurement of plasma TIMP-1 cannot be used for the identification of adenomatous or hyperplastic polyps of the large intestine.
Assuntos
Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Pólipos do Colo/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Tissue inhibitor of matrix metalloproteases 1 (TIMP-1) inhibits the proteolytic activity of matrix metalloproteases and hereby prevents cancer invasion. However, TIMP-1 also possesses other functions such as inhibition of apoptosis, induction of malignant transformation and stimulation of cell-growth. We have previously demonstrated that TIMP-1 is elevated in blood from colorectal cancer patients and that high TIMP-1 levels predict poor prognosis. To clarify the role of TIMP-1 in colorectal tumorigenesis, the expression pattern of TIMP-1 in benign and malignant colorectal tumors was studied. In all of 24 cases of colorectal adenocarcinoma TIMP-1 mRNA was detected by in situ hybridization. In all cases TIMP-1 expression was found in fibroblast-like cells located at the invasive front but was seen only sporadically in normal mucosa. No TIMP-1 mRNA was seen in any of the cases in benign or malignant epithelial cells, in vascular cells or smooth muscle cells. Comparison of sections processed for TIMP-1 in situ hybridization with sections immunohistochemically stained with antibodies against TIMP-1 showed good correlation between TIMP-1 mRNA and immunoreactivity. Combining TIMP-1 in situ hybridization with immunohistochemical staining for alpha-smooth muscle actin or CD68 showed TIMP-1 mRNA in myofibroblasts but not in macrophages. TIMP-1 mRNA was detected in 2 of 7 adenomatous polyps in the adenoma area: in both cases associated with focal stromal inflammation at the epithelial-stromal interface. In conclusion, TIMP-1 expression is a rare event in benign human colon tissue but is highly expressed by myofibroblasts in association with invading colon cancer cells.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Inibidor Tecidual de Metaloproteinase-1/farmacologia , Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Estudos de Casos e Controles , Transformação Celular Neoplásica , Neoplasias Colorretais/diagnóstico , Diagnóstico Diferencial , Fibroblastos/fisiologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Invasividade Neoplásica , RNA Mensageiro/análise , RNA Mensageiro/biossínteseRESUMO
BACKGROUND: We previously found differences in total concentrations of tissue inhibitor of metalloproteinases 1 (TIMP-1) in plasma from donors and cancer patients. Because TIMP-1 can exist in more than one molecular form, a new immunoassay to specifically detect free TIMP-1 was developed and concentrations were determined in plasma from healthy donors and colorectal cancer (CRC) patients. METHODS: We established and validated an immunoassay for the specific measurement of free TIMP-1 that uses a polyclonal anti-TIMP-1 antibody for capture and a monoclonal anti-TIMP-1 antibody that binds only free TIMP-1 for detection of antigen. Plasma samples from healthy donors and CRC patients were assayed for free TIMP-1. Total TIMP-1 was measured by our previously published assay. RESULTS: The mean (SD) concentrations of free TIMP-1 were similar in citrate [55.5 (11.5) microg/L] and EDTA plasma [58.9 (13.3) microg/L] from 76 donors (r(2) = 0.82). In 154 donors, the ratio of free TIMP-1 [mean (SD), 64.5 (18.0) microg/L] to total TIMP-1 [83.8 (19.8) microg/L] in EDTA plasma was 0.77. Plasma concentrations of free and total TIMP-1 correlated significantly to age (free, r(2) = 0.19; total, r(2) = 0.27; P <0.0001), increasing 50% over an age span of 45 years. Free and total TIMP-1 were significantly increased in CRC patients (P <0.0001), whereas the ratio of free to total TIMP-1 (mean, 0.58) was significantly lower than in donors. CONCLUSIONS: Most of the TIMP-1 in donor plasma is present in its free form, and free TIMP-1 increases with age. Free and total TIMP-1 are increased in CRC patient plasma, but the ratio of free to total TIMP-1 is significantly lower in these patients than in donors.
Assuntos
Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes , Ácido Cítrico , Neoplasias Colorretais/sangue , Ácido Edético , Ensaio de Imunoadsorção Enzimática , Humanos , Metaloendopeptidases/metabolismo , Pessoa de Meia-Idade , Valores de Referência , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
Extracellular proteolytic enzymes of the urokinase-type plasminogen activator (uPA) system and the family of metalloproteinases (MMPs) catalyse the matrix degradation and remodelling processes characteristic of invasive malignant disorders. In a cohort of 50 patients with chronic myeloproliferative disorders (MPD) serum markers for collagen metabolism were compared to plasma levels of enzymes of the uPA and MMP system. Serum aminoterminal propeptide of type III procollagen (S-PIIINP) (P < 0.0001) concentration was significantly higher in the patients (median 3.7 micro g/L vs. 2.5 micro g/L) compared with controls. In a subgroup analysis comprising patients with myelofibrosis (MF), polycythaemia vera (PV) and essential thrombocythaemia (ET), respectively, S-PIIINP levels differed significantly with the highest values found in patients with MF (MF vs. PV vs. ET; P = 0.0027). Serum concentration of carboxyterminal telopeptide of type I collagen (S-ICTP) (P = 0.0006), reflecting type I collagen degradation, was significantly higher in patients compared with controls (median 4.0 micro g/L vs. 2.7 micro g/L). When comparing S-ICTP measurements between patient subgroups and controls there were only significantly higher values among MF and PV patients (MF vs. controls; P < 0.0001, PV vs. controls; P = 0.0016). A significant correlation between the marker for collagen synthesis (S-PIIINP) and degradation (S-ICTP) (r = 0.59; P < 0.0001) was demonstrated. A correlation analysis between serum markers for bone marrow remodelling processes (S-PIIINP, S-ICTP and S-hyaluronan) and plasma-soluble urokinase plasminogen receptor (suPAR) disclosed a significant relationship between suPAR and S-PIIINP (r = 0.48; P = 0.0009), S-hyaluronan (r = 0.56; P < 0.0001) and S-ICTP (r = 0.47; P = 0.0013), respectively. Plasma levels of MMP-2 and -9 were not correlated to serum markers for collagen metabolism. These findings suggest that enzymes of the uPA system might participate in the bone marrow remodelling processes characteristic of MPD.