Correlation of serum Klotho, fetuin-A, and MGP levels with coronary artery calcification in maintenance hemodialysis patients.

OBJECTIVE: This study was to investigate the role of serum Klotho, fetuin-A, and Matrix Gla Protein (MGP) in Coronary Artery Calcification (CAC) in patients with Maintenance Hemodialysis (MHD) and their predictive value for CAC. METHODS: 100 patients receiving MHD were selected. Serum Klotho, fetuin-A, and MGP levels were detected by ELISA. CAC scores were assessed by coronary CT scan. Multifactor analysis was used to evaluate the risk factors affecting CAC. The ability of serum Klotho, fetuin-A, and MGP levels to diagnose CAC was evaluated by receiver operating characteristic curves. RESULTS: Serum Klotho, fetuin-A, and MGP were independent risk factors for CAC. Serum Klotho, fetuin-A, and MGP were valuable in the diagnosis of CAC in MHD patients. CONCLUSION: There is a close relationship between Klotho, fetuin-A, and MGP levels in MHD patients and CAC.

Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers.

Background: Nephrolithiasis has been associated with bone loss and vascular calcification (VC), reflecting abnormal extraosseous calcium deposition. Fetuin-A (Fet-A) acts as a potent inhibitor of ectopic mineralization. The aim of the present study was to evaluate the prevalence of VC in stone formers (SF) and non-stone formers (NSF) and to investigate potential determinants of VC among SF, including circulating levels of Fet-A and bone microarchitecture parameters. Methods: Abdominal aortic calcification (AAC) was assessed using available computed tomography in SF and in age-, sex-, and BMI-matched NSF (potential living kidney donors). Serum Fet-A was measured in stored blood samples from SF. Bone microarchitecture parameters were obtained as a post hoc analysis of a cross-sectional cohort from young SF evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: A total of 62 SF (38.0 [28.0−45.3] years old) and 80 NSF (40.0 [37.0−45.8] years old) were included. There was no significant difference in AAC scores between SF and NSF. However, when dividing SF according to mean AAC score, below <5.8% (n = 33) or above ≥5.8% (n = 29), SF with higher AAC presented significantly higher BMI and tibial cortical porosity (Ct.Po) and significantly lower serum HDL, klotho, Fet-A, and eGFR. Urinary calcium did not differ between groups, but fractional excretion of phosphate was higher in the former. Upon multivariate regression, BMI, serum Fet-A, and tibial Ct.Po remained independently associated with AAC. Conclusions: This study suggests an association between reduced circulating Fet-A levels and increased bone Ct.Po with VC in SF.

Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST / Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction

Resumo Fundamento A fetuína-A é um fator anti-inflamatório e anticalcificação envolvido no curso da doença arterial coronariana (DAC). Em alinhamento com essas funções, investigou-se a fetuína-A como marcador de risco cardiovascular em vários estudos. Porém, a associação entre a fetuína-A e o prognóstico dos pacientes com DAC ainda é controversa. Objetivos O presente estudo foi conduzido para identificar a associação entre o nível de fetuína-A sérica e doença cardiovascular (DCV) de longo prazo e a mortalidade global por infarto do agudo do miocárdio por supradesnivelamento do segmento ST (STEMI). Métodos Foram cadastrados no estudo cento e oitenta pacientes consecutivos com STEMI. A população do estudo foi dividida em subgrupos (mais baixo, ≤288 µg/ml; e mais alto, >288 µg/ml) de acordo com a mediana do nível de fetuína-A. Dados de acompanhamento clínico foram obtidos por contato telefônico anual com pacientes ou familiares. As causas das mortes também foram confirmadas pelo banco de dados de saúde nacional. P-valores bilaterais <0,05 foram considerados estatisticamente significativos. Resultados Durante um acompanhamento médio de 10 anos, foram registradas 71 mortes, das quais 62 foram devidas a DCV. Identificou-se um índice de mortalidade global e por DCV significativamente mais alto no grupo com nível de fetuína-A mais baixo que no grupo com nível de fetuína-A mais alto (44% versus 24%, p= 0,005; 48% versus 31%, p= 0,022, respectivamente). Nas análises de risco proporcionais por regressão de Cox, detectou-se que a fetuína-A era um preditor independente de mortalidade global e por DCV. Conclusões A baixa concentração de fetuína-A está associada ao prognóstico de longo prazo ruim pós-STEMI, independentemente de fatores de risco cardiovascular tradicionais. Nossos achados fortaleceram estudos prévios demonstrando consistentemente o papel determinante dos mediadores anti-inflamatórios em síndromes coronárias agudas.

Abstract Background Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial. Objectives The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI). Methods One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant. Results During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality. Conclusions Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up / Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Abstract Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Resumen Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up.

Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary studies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad cardiovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p < 0.001). El mejor punto de corte fue de 5 (sensibilidad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Nonalcoholic Fatty Liver Disease in Nonobese Subjects of African Origin Has Atypical Metabolic Characteristics.

BACKGROUND: Nonobese nonalcoholic fatty liver disease is reported in several populations. However, because persons of African origin display unique fat accumulation, insulin resistance, and lipid profiles, we investigated fatty liver in nonobese persons of African origin. METHOD: We recruited 78 urban Jamaican volunteers. CT was used to estimate liver and abdominal fat and dual-energy X-ray absorptiometry to measure body composition. Fasting blood was collected for lipids, alanine aminotransferase (ALT), adiponectin, and fetuin-A. Homeostatic model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), insulinogenic index (IGI), and oral disposition index (oDI) were calculated after a 75-g oral glucose tolerance test. RESULTS: Fifty-two percent of participants were male; mean (±SD) age was 28.5 ± 7.8 years, and body mass index was 22.4 ± 3.0 kg/m2. Mean liver attenuation (MLA) and liver/spleen (LS) ratio, both inversely correlated to liver fat, were 62.8 ± 4.3 HU and 1.2 ± 0.1, respectively; 3.8% of participants had liver fat >30% (LS ratio < 1). In age, sex, and BMI-adjusted correlations, MLA was negatively associated with weight (r = -0.30; P = 0.009) and height (r = -0.28; P = 0.017) and was associated with fasting glucose (r = 0.23; P = 0.05), fasting insulin (r = 0.42; P ≤ 0.001) and HOMA-IR (r = 0.35; P = 0.004). Serum lipids, ALT, adiponectin, fetuin-A, WBISI, IGI, and oDI were not associated with liver fat. CONCLUSIONS: In nonobese Afro-Caribbean participants, greater liver fat was associated with weight and height and lower fasting insulin and hyperinsulinemia appears to be influential in the reduction of NAFLD. These findings may be influenced by ethnicity, body size, and method of estimating liver fat.

Colorimetric Paper-Based Immunosensor for Simultaneous Determination of Fetuin B and Clusterin toward Early Alzheimer's Diagnosis.

Alzheimer's disease is a devastating condition characterized by a progressive and slow brain decay in elders. Here, we developed a paper-based lateral flow immunoassay for simultaneous and fast determination of Alzheimer's blood biomarkers, fetuin B and clusterin. Selective antibodies to targeted biomarkers were immobilized on gold nanoparticles (AuNPs) and deposited on paper pads. After adding the sample on the paper-based device, the biofluid laterally flows toward the selective antibody, permitting AuNP-Ab accumulation on the test zone, which causes a color change from white to pink. Image analysis was performed using a customized algorithm for the automatic recognition of the area of analysis and color clustering. Colorimetric detection was compared to electrochemical methods for the precise quantification of biomarkers. The best performance was found for the color parameter "L*". Good linearity (R2 = 0.988 and 0.998) and reproducibility (%RSD = 2.79% and 1.82%, N = 3) were demonstrated for the quantification of fetuin B and clusterin, respectively. Furthermore, the specificity of the immunosensor was tested on mixtures of proteins, showing negligible cross-reactivity and good performance in complex environments. We believe that our biosensor has a potential for early-stage diagnosis of Alzheimer's disease and toward a better understanding of Alzheimer's developing mechanisms.

Prediction of gestational diabetes mellitus in the first trimester: comparison of maternal fetuin-A, N-terminal proatrial natriuretic peptide, high-sensitivity C-reactive protein, and fasting glucose levels

ABSTRACT Objective We investigated the utility of maternal fetuin-A, N-terminal proatrial natriuretic peptide (pro-ANP), high-sensitivity C-reactive protein (hs-CRP), and fasting glucose levels at 11-14 gestation weeks for predicting pregnancies complicated by gestational diabetes mellitus (GDM). Subjects and methods This prospective cohort study included 327 low-risk pregnant women who completed antenatal follow-up at a tertiary research hospital between January and April 2014. Maternal blood samples were collected between 11-14 gestational weeks in the first trimester of pregnancy and then stored at -80 °C until further analyses. During follow-up, 29 (8.8%) women developed GDM. The study population was compared 1:2 with age- and body mass index-matched pregnant women who did not develop GDM (n = 59). Fasting plasma glucose (FPG) levels and serum fetuin-A, pro-ANP, and hs-CRP levels were measured using automated immunoassay systems. Results There was a significant negative correlation between fetuin-A and hs-CRP (CC = -0.21, p = 0.047) and a positive correlation between FPG and hs-CRP (CC = 0.251, p = 0.018). The areas under the receiver operating characteristic curve for diagnosing GDM were 0.337 (p = 0.013), 0.702 (p = 0.002), and 0.738 (p < 0.001) for fetuin-A, hs-CRP, and FPG, respectively. The optimal cut-off values were > 4.65, < 166, and > 88.5 mg/dL for maternal hs-CRP, fetuin-A, and FPG, respectively. Conclusion Reduced fetuin-A, elevated hs-CRP, and FPG levels in women in the first trimester can be used for the early detection of GDM. Further research is needed before accepting these biomarkers as valid screening tests for GDM.

Effects of exercise training on Fetuin-a in obese, type 2 diabetes and cardiovascular disease in adults and elderly: a systematic review and Meta-analysis.

BACKGROUND: Elevated levels of fetuin-A are associated with increased risks of metabolic syndrome, type 2 diabetes and nonalcoholic fatty liver disease. This meta-analysis investigated whether exercise interventions can reduce fetuin-A in adults. METHODS: We searched clinical trials that objectively assessed fetuin-A and included study arms with exercise intervention. The pre-intervention and post-intervention data were used for meta-analysis. The effect sizes were calculated as standardized mean differences or changes in fetuin-A and expressed as Hedges' g using random-effects models. RESULTS: The overall Hedges' g for fetuin-A in all included interventions was - 0.640 (95%CI - 1.129 to - 0.151; n = 9), but this effect was not observed in obese (g = - 0.096; 95%CI, - 0.328 to 0.135) and type 2 diabetes/dysglycemia (g = - 0.56; 95%CI, - 1.348 to 0.236) individuals. Additionally, the random-effects meta-regression analysis showed that there was not a greater decrease in fetuin-A in individuals who achieved greater body mass index reductions (regression coefficient = 0.065; 95%CI, - 0.185 to 0.315). CONCLUSION: Supervised exercise is associated with reductions in fetuin-A levels in adults and elderly. However, the results of the present meta-analysis should be interpreted with caution because of the variety of type of exercises and individual obesity related-disorders involve. Therefore, additional high-quality randomized controlled trials describing the effect of supervised exercise interventions on fetuin-A in adults are still needed. .

Circulating Triglycerides and the Association of Triglycerides with Dietary Intake Are Altered by Alpha-2-Heremans-Schmid Glycoprotein Polymorphisms.

BACKGROUND: Circulating fetuin-A (FetA) inhibits insulin receptor signaling and activates the toll-like receptor 4 proinflammatory cascade; thus, it may contribute to metabolic syndrome. Polymorphisms in alpha-2-Heremans-Schmid glycoprotein (AHSG), the gene which codes FetA, may influence metabolic syndrome progression in higher-risk ethnic groups. We aimed to identify whether individual variation in AHSG influences biomarkers of metabolic disease and obesity in young Mexican adults. METHODS: The participants were Mexican college applicants (18-25 years, n = 641). Dietary intake, anthropometric data, and blood for the analysis of biomarkers and genetics were collected. Single nucleotide polymorphisms (SNPs) in AHSG (rs2518136 and rs4917) were genotyped. RESULTS: Neither AHSG SNP was associated with body mass index (BMI) or waist circumference. rs4917 C allele carriers had lower triglycerides (TG) than T allele homozygotes (98.85 ± 2.3 vs. 112.2 ± 5.2 mg/dL, p = 0.0113). BMI was strongly associated with TG (p < 0.0001) regardless of genotype. The relationship between circulating TG and dietary intake of carbohydrates and saturated fat was significant in rs4917 CT allele heterozygotes only (p = 0.03 and p = 0.02, respectively). CONCLUSIONS: rs4917 T allele carriers had higher TG. This relationship was exaggerated in individuals with overweight and obesity. Dietary intake was significantly associated with TG in only those with heterozygosity at rs4917, suggesting that these individuals may be more susceptible to dietary interventions.

Vascular Calcification Regulation by Exosomes in the Vascular Wall.

Vascular calcification is a tightly regulated process that increases during ageing and occurs mainly in patients with diabetes and chronic renal failure. Exosomes are small membrane vesicles that are synthesized in a particular population of endosomes, also called multivesicular bodies, by inside budding into the lumen of the compartment. After fusion of exosome with the plasma membrane, these internal vesicles are secreted. Exosomes have a defined set of membrane and cytosolic proteins. The physiological function of exosomes is still a matter of debate. Investigators implicated microvesicles/exosomes as a specific signaling mechanism to induce vascular mineralization during vascular smooth muscle cells phenotypic transition. Vascular wall from healthy individual exhibit exosomes loaded with calcification inhibitors such as Fetuin A and MGP. Conversely, calcifying conditions induce secretion of exosomes, characterized by decreased calcifying inhibitors and increased phosphatidyl serine and Annexin A6 content, which serves as a nidus for vascular calcification.

Inflammatory Markers in Obese Adolescents with Type 2 Diabetes and Their Relationship to Hepatokines and Adipokines.

OBJECTIVES: To analyze inflammatory markers, adipokines, and hepatokines in obese adolescents with and without type 2 diabetes mellitus (T2DM). STUDY DESIGN: We studied high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, interleukin-1ß, and interferon-γ, the hepatokines (fetuin-A and fibroblast growth factor [FGF]-21), and the adipokines (adiponectin and leptin) in a cross-sectional study of 74 predominately Caucasian adolescents with T2DM aged 12-18 years and in 74 body mass index (BMI)-, age-, and sex-matched controls. RESULTS: Adolescents with T2DM had significantly higher concentrations of hsCRP, TNF-α, and interleukin-1ß compared with obese controls without T2DM. Interferon-γ was not detectable in obese adolescents with or without T2DM. In multiple linear regression analysis, hsCRP was significantly associated with FGF-21 and BMI, but not with hemoglobin A1c, adiponectin, leptin, fetuin-A, sex, or age. TNF-α was significantly related negatively to leptin, positively to BMI, but not to hemoglobin A1c, adiponectin, fetuin-A, FGF-21 sex, or age in multiple linear regression analysis. CONCLUSIONS: Increased inflammatory markers are associated with T2DM in adolescents. Because hsCRP was related to FGF-21 and TNF-α was associated with leptin, these findings suggest a link between increased levels of these adipokines and hepatokines and chronic inflammation. Future longitudinal studies in humans are necessary to confirm these hypotheses.

Comparison of pre- and post-levothyroxine high-sensitivity c-reactive protein and fetuin-a levels in subclinical hypothyroidism

OBJECTIVE: The objective of this trial was to determine the levels of inflammatory markers, high-sensitivity C-reactive protein and fetuin-A pre- and post-levothyroxine treatment in cases of subclinical hypothyroidism. MATERIALS AND METHODS: A total of 32 patients with a diagnosis of subclinical hypothyroidism and a control group of 30 healthy individuals were tested for high-sensitivity C-reactive protein and fetuin-A, followed by the administration of 50 µg of levothyroxine in the patient group for 3 months. During the post-treatment stage, high-sensitivity C-reactive protein and fetuin-A levels in the patient group were re-assessed and compared with pre-treatment values. RESULTS: Pre-treatment levels of both high-sensitivity C-reactive protein and fetuin-A were observed to be higher in the patient group than in the control group. The decrease in high-sensitivity C-reactive protein levels during the post-treatment stage was not statistically significant. However, the decrease observed in post-treatment fetuin-A levels was found to be statistically significant. CONCLUSION: The decrease in fetuin-A levels in subclinical hypothyroidism cases indicates that levothyroxine treatment exerts anti-inflammatory and anti-apoptotic effects. Although the decrease in high-sensitivity C-reactive protein levels was statistically non-significant, it is predicted to reach significance with sustained treatment. .

Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study

OBJECTIVES: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. METHODS: Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. CONCLUSION: Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis. .

Actualización en la fisiopatología de la preeclampsia: update

La preeclampsia constituye una de las complicaciones más frecuentes y a la vez más serias de la gestación y contribuye de manera significativa a la mortalidad materna y perinatal. No obstante los avances en el estudio de la preeclampsia, aún no está del todo esclarecido su mecanismo fisiopatológico. En este capítulo, intentamos revisar nuevas teorías propuestas acerca de su fisiopatología. Los aspectos genéticos y angiogénicos serán revisados en otros capítulos de este simposio.

Preeclampsia is one of the most frequent and serious disorders of pregnancy. It is a significant contributor of maternal and perinatal mortality worldwide. An important amount of research has been devoted in the research of preeclampsia in the recent years; nonetheless, its pathophysiology is yet to be completely understood. In this review, we will discuss new proposed theories on the pathophysiology of preeclampsia. Genetic and angiogenic aspects of preeclampsia will be reviewed elsewhere in this issue.

Fetuin-A levels in hyperthyroidism

OBJECTIVE: Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. METHODS: We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. RESULTS: Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1). Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. CONCLUSION: Our findings suggest that hyperthyroidism influences fetuin-A levels.

The effect of Helicobacter pylori eradication on macrophage migration inhibitory factor, C-reactive protein and fetuin-a levels.

OBJECTIVES: To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of high-sensitivity C-reactive protein (hs-CRP), macrophage migration inhibitory factor and fetuin-A in patients with dyspepsia who are concurrently infected with H. pylori. METHODS: H.pylori infection was diagnosed based on the 14C urea breath test (UBT) and histology. Lansoprazole 30 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily were given to all infected patients for 14 days; 14C UBT was then re-measured. In 30 subjects, migration inhibitory factor, fetuin-A and hs-CRP levels were examined before and after the eradication of H. pylori infection and compared to levels in 30 healthy subjects who tested negative for H. pylori infection. RESULTS: Age and sex distribution were comparable between patients and controls. Migration inhibitory factor and hs-CRP levels were higher, and fetuin-A levels were lower, in H. pylori-infected patients (p<0.05). Following eradication of H. pylori, migration inhibitory factor and hs-CRP levels were significantly decreased, whereas fetuin-A levels were increased. However, eradication of the organism did not change lipid levels (p>0.05). CONCLUSION: These findings suggest that H. pylori eradication reduces the levels of pro-inflammatory cytokines such as migration inhibitory factor and hs-CRP and also results in a significant increase in anti-inflammatory markers such as fetuin-A.

The effect of Helicobacter pylori eradication on macrophage migration inhibitory factor, C-reactive protein and fetuin-a levels

OBJECTIVES: To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of high-sensitivity C-reactive protein (hs-CRP), macrophage migration inhibitory factor and fetuin-A in patients with dyspepsia who are concurrently infected with H. pylori. METHODS: H.pylori infection was diagnosed based on the 14C urea breath test (UBT) and histology. Lansoprazole 30 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily were given to all infected patients for 14 days; 14C UBT was then re-measured. In 30 subjects, migration inhibitory factor, fetuin-A and hs-CRP levels were examined before and after the eradication of H. pylori infection and compared to levels in 30 healthy subjects who tested negative for H. pylori infection. RESULTS: Age and sex distribution were comparable between patients and controls. Migration inhibitory factor and hs-CRP levels were higher, and fetuin-A levels were lower, in H. pylori-infected patients (p<0.05). Following eradication of H. pylori, migration inhibitory factor and hs-CRP levels were significantly decreased, whereas fetuin-A levels were increased. However, eradication of the organism did not change lipid levels (p>0.05). CONCLUSION: These findings suggest that H. pylori eradication reduces the levels of pro-inflammatory cytokines such as migration inhibitory factor and hs-CRP and also results in a significant increase in anti-inflammatory markers such as fetuin-A.