DOCSLIB.ORG

Relationship of Fibronectin to C-Reactive Protein, Ceruloplasmin, Alpha-1 Antitrypsin, and Transferrin in Septicemic Children

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Relationship of Fibronectin to C-Reactive Protein, Ceruloplasmin, Alpha-1 Antitrypsin, and Transferrin in Septicemic Children J. Clin. Biochem. Nutr., 22, 177-181, 1997 Relationship of Fibronectin to C-Reactive Protein, Ceruloplasmin, Alpha-1 Antitrypsin, and Transferrin in Septicemic Children Nermin GULER,1,*Ulker ONES,1Nihal SALMAYENLI,2 Isik YALCIN,1Ahmet SIVAS,2and Nuran SALMAN1 1Department of Pediatrics and Department of Biochemistry, Istanbul University, Faculty of Medicine, Capa, Istanbul, Turkey (Received December 2, 1996) Summary We investigated the relationship between plasma levels of fibronectin and other acute-phase reactant proteins such as C-reactive protein, alpha-1 antitrypsin, ceruloplasmin, and transferrin in children with severe septicemia. The study included 33 septicemic patients and 10 normal children. Mean plasma fibronectin level was significantly lower in patients on admission (204.7±57.3 mg/dl), and was higher after recovery (349.3±89 mg/dl), than in normal children (300.2•}65 mg/dl). No sig- nificant difference was found between the mean plasma fibronectin levels of patients with and without meningitis. After the recovery, fibronectin correlated positively with age. No correlation was found between plasma fibronectin and C-reactive protein, transferrin, ceruloplasmin, or alpha-1 antitrypsin levels at any stage of the disease. We concluded that fibronec- tin has no modulating effect on acute-phase responses of these proteins in severe septicemia. Key Words: fibronectin, septicemia, acute-phase reactants Fibronectin is an important opsonic glycoprotein present on most cell sur- faces and in extracellular fluids. The protein interacts with a number of macro- molecules on cell surfaces, and plays an important role in opsonic functions. Fibronectin is synthesized by a variety of cells, including epithelial cells, endo- thelial cells, fibroblasts, platelets, neutrophils, macrophages, and hepatocytes. The liver is the main source of circulating fibronectin [1-3]. The plasma fibronectin level is depleted in patients with sepsis, trauma, burns, or shock, and this reduction is associated with reticuloendothelial system dysfunc- * To whom correspondence should be addressed . 177 178 N, GULER et al. tion [4, 5]. Studies have shown that lowered fibronectin concentrations decrease resistance to sepsis and that fibronectin levels decrease further secondary to sepsis itself [6]. The interaction of fibronectin with reticuloendothelial system dysfunction during acute bacterial sepsis is not fully understood. The purpose of the present prospective study was to investigate the relationship between plasma levels of fibronectin and some other acute-phase reactant proteins such as C-reactive protein, alpha-1 antitrypsin, ceruloplasmin, and transferrin in children with severe septicemia. MATERIALSAND METHODS This study included 33 children (13 females and 20 males) at the age of 3-72 months (median: 24 months) when they were referred to Istanbul Medical Faculty, Department of Pediatrics, because of severe septicemia. All children were evaluat- ed from the results of clinical examination, complete blood cell count, lumbar puncture for routine studies, and cultures. Septicemia was confirmed by positive blood cultures and/or by positive latex particle agglutination tests in blood. Microorganisms identified were Staphylococcus aureus in 5 (15.1%), Streptococcus pneumoniae in 3 (9%), Neisseria meningitidis in 20 (60.6%), and Klebsiella pneu- moniae in 5 (15.1%) patients. Bacterial meningitis was confirmed in 18 (54.5%) of the patients. Patients with favorable outcome were selected for the study. Blood samples were obtained by venipuncture in a tube with citrate for fibronectin and without citrate for C-reactive protein, transferrin, ceruloplasmin, and alpha-1 antitrypsin determinations. The measurements were performed by use of radial immunodiffusion plates (Boehringwerke AG, Marburg, Germany). Simultaneous determinations of these parameters were performed in the blood obtained on the first day of admission and on the day of discharge from the hospital, the interval between the two ranging from 14 to 21 days. Control fibronectin values were obtained from 10 healthy children (median age: 21 months; range: 7-72 months). The distribution of the variables were compared with a standard normal distribution by the Kolmogorov-Smirnov test. Two-tailed t-tests were used to compare means. The correlations between variables that were normally distributed were tested with Pearson's linear correlation; and the ones that were not normally distributed, with Spearman's rank correlation. RESULTS At the initial stage of septicemia, the plasma fibronectin levels were 204.7+ 57.3 mg/dl (mean + SD) for patients and 300.2±65 mg/dl for normal children. Patients showed a significantly lower mean value than normal children (p<0.001). Twenty-five (75.7%) patients had fibronectin levels below the lower limit for J. Clin. Biochem. Nutr. FIBRONECTIN AND ACUTE-PHASE REACTANTS 179 Table 1. Mean plasma levels of fibronectin, C-reactive protein, transferrin, ceruloplasmin, and alpha-1 antitrypsin at the initial stage and after recovery. Values are the mean ± SD (n = 33). *p <0.01; * *p <0.001. NS, not significant. normal children (mean± 1SD). No significant difference was found between the mean plasma fibronectin levels of patients with and without meningitis (214.11 ± 40.6 mg/dl and 193.6+72.5 mg/dl, respectively). Alpha-1 antitrypsin and cerulo- plasmin levels correlated positively with age (r=0.41; p<0.05 and r = 0.46; p < 0.01, respectively). Alpha-1 antitrypsin levels also had correlation with C-reactive protein and ceruloplasmin levels (r=0.37; p<0.05 and r=0.35; p<0.05, respec- tively). Fibronectin, however, did not show significant correlation either with age or with any of these acute-phase reactants investigated in the acute stage of septicemia. After the recovery, the plasma fibronectin level (mean: 349.3 + 89 mg/dl) was higher in the septicemic patients than in the normal children, but this difference was not statistically significant. Sixteen (48.5%) patients had fibronectin values higher than normal. These increased levels also did not show any correlation with other acute-phase proteins. Plasma fibronectin correlated positively with the age of the patients. In this stage, plasma levels of C-reactive protein had positive correla- tion with ceruloplasmin levels (r=0.48; p<0.01). Mean plasma levels of fibronectin, C-reactive protein, transferrin, ceruloplas- min, and alpha-1 antitrypsin at the initial stage and after recovery are shown in Table 1. The differences between the two stages for fibronectin, C-reactive protein, transferrin, and alpha-1 antitrypsin levels were statistically significant (p<0.001) but the difference between ceruloplasmin levels was not. Positive correlations were found in C-reactive protein (r=0.59; p<0.001), ceruloplasmin (r=0.53; p<0.01) and transferrin (r=0.47; p<0.01) levels and no correlations were found in fibronectin and alpha-1 antitrypsin levels between the initial and recovery stages. DISCUSSION Fibronectin is a protein that participates in a variety of unrelated biologic processes within tissues. Data from experimental studies imply that fibronectin has a central role in the inflammatory response [3]. The mechanism by which fibro- nectin synthesis is regulated at the cellular level is unknown. This protein may augment phagocytosis, modulate adherence, and prepare the reticuloendothelial Vol. 22, No. 3, 1997 180 N. GULER et al. system for clearance of complement- or antibody-coated material such as micro- organisms and cellular debris. Plasma concentrations of fibronectin typically decrease during septic episodes in children and adults [5-7]. Probably, the reason for this is increased consump- tion of fibronectin secondary to reticuloendothelial system clearance of fibronec- tin-coated material. Fibronectin deficiency and resultant reticuloendothelial sys- tem impairment may have important effects on the ability of infants to clear bacterial infections [6]. Newborn infants have lower plasma fibronectin levels, which increase postnatally and reach adult values by approximately 2 months of age [8]. Patients included in this study were severely ill and had fibronectin values in the acute phase of sepsis significantly lower than those of normal children due to peripheral consumption. We couldn't find any correlation initially between the fibronectin level and that of some of acute-phase reactants such as C-reactive protein, transferrin, ceruloplasmin, and alpha-1 antitrypsin, which are proteins synthesized primarily in the liver. Acute starvation and calorie deprivation are important factors altering he- patic functions and contributing to the reticuloendothelial system depression in septic children [9]. This is associated with low plasma fibronectin concentrations [10]. Transferrin and ceruloplasmin are also known indices of nutritional status [11]. The absence of correlation between these proteins suggests that regulation of the synthesis and degradation must be different among these proteins. After the recovery from the clinical infection, the concentrations of fibro- nectin in plasma increased above normal levels, suggesting the increased produc- tion. Polin also had found high fibronectin levels after recovery from sepsis [12]. It is likely that bacterial sepsis has the capacity both to increase and to decrease plasma fibronectin levels. This increased levels also did not show any correlation with other acute-phase reactants investigated. Substitution therapy with intravenous fibronectin preparations has been used in septicemia,
Load more

Recommended publications
  • Types of Acute Phase Reactants and Their Importance in Vaccination (Review)
    BIOMEDICAL REPORTS 12: 143-152, 2020 Types of acute phase reactants and their importance in vaccination (Review) RAFAAT H. KHALIL1 and NABIL AL-HUMADI2 1Department of Biology, College of Science and Technology, Florida Agricultural and Mechanical University, Tallahassee, FL 32307; 2Office of Vaccines, Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, MD 20993, USA Received May 10, 2019; Accepted November 25, 2019 DOI: 10.3892/br.2020.1276 Abstract. Vaccines are considered to be one of the most human and veterinary medicine. Proteins which are expressed cost-effective life-saving interventions in human history. in the acute phase are potential biomarkers for the diagnosis The body's inflammatory response to vaccines has both of inflammatory disease, for example, acute phase proteins desired effects (immune response), undesired effects [(acute (APPs) are indicators of successful organ transplantation phase reactions (APRs)] and trade‑offs. Trade‑offs are and can be used to predict the ameliorative effect of cancer more potent immune responses which may be potentially therapy (1,2). APPs are primarily synthesized in hepatocytes. difficult to separate from potent acute phase reactions. The acute phase response is a spontaneous reaction triggered Thus, studying acute phase proteins (APPs) during vaccina- by disrupted homeostasis resulting from environmental distur- tion may aid our understanding of APRs and homeostatic bances (3). Acute phase reactions (APRs) usually stabilize changes which can result from inflammatory responses. quickly, after recovering from a disruption to homeostasis Depending on the severity of the response in humans, these within a few days to weeks; however, APPs expression levels reactions can be classified as major, moderate or minor.
    [Show full text]
  • Normal Fibronectin Levels As a Function of Age in the Pediatric Population
    Pediatr. Res. 17: 482-485 (1983) Normal Fibronectin Levels as a Function of Age in the Pediatric Population MICHAEL H. MCCAFFERTY,'~"MARTHA LEPOW, THOMAS M. SABA,'21' ESHIN CHO, HILAIRE MEUWISSEN, JOHN WHITE, AND SHARON F. ZUCKERBROD Departments of Physiology and Pediatrics, Albany Medical College of Union University, Albany, New York, USA Summary pediatric population with age has not been reported. This may be important in terms of appropriate interpretation of prevailing Fibronectin is an important non-immune opsonic protein influ- levels in children with various disease states, because normal encing phagocytic clearance of blood-borne nonbacterial particu- concentrations in children may be different from normal levels in lates which may arise in association with septic shock, tissue adults. This study was designed to measure fibronectin levels in a injury, and intravascular coagulation. In the present study, serum large group (n = 114) of normal children in order to define its fibronectin was measured by both electroimmunoassay as well as normal concentration as a function of age. rapid immunoturbidimetric assay in healthy children (n = 114) ranging in age from 1 month to 15 years in order to delineate the temporal alterations in fibronectin with age. Normal adult serum MATERIALS AND METHODS fibronectin concentrations are typically 220 pg/ml + 20 pg/ml. Serum concentration is 3540% lower than normal plasma con- Healthy children (n = 114) ranging in age from 1 month to 15 centration due to the binding of fibronectin to fibrin during clot years were seen as outpatients or as inpatients for minor surgical formation. Children between 1-12 months of age had significantly procedures.
    [Show full text]
  • Serum Alpha2-Macroglobulin, Transferrin, Albumin, and Igg Levels in Preeclampsia
    J. clin. Path., 1970, 23, 514-516 J Clin Pathol: first published as 10.1136/jcp.23.6.514 on 1 September 1970. Downloaded from Serum alpha2-macroglobulin, transferrin, albumin, and IgG levels in preeclampsia C. H. W. HORNE, P. W. HOWIE, AND R. B. GOUDIE From the University Departments ofPathology and Obstetrics and Gynaecology, Western Infirmary, Glasgow SYNOPSIS A radial immunodiffusion technique has been used to measure levels of four serum proteins in preeclampsia with or without proteinuria and in normal pregnant and non-pregnant controls. In preeclampsia unaccompanied by proteinuria, albumin and transferrin levels are similar to those found in the normal pregnant controls, but there are significant falls in 0x2-macroglobulin and IgG. When preeclampsia is accompanied by proteinuria there is a marked fall in albumin and an increase in o'2-macroglobulin. Since oU2-macroglobulin has antiplasmin activity it is possible that increased levels of this protein in preeclampsia accom-copyright. panied by proteinuria contribute to the intravascular coagulation which has been described in this disorder. Both in pregnancy and the nephrotic syndrome tension (bloodpressurehigher than 140/90mm Hg) increased levels of serum x2-macroglobulin have on two or more separate occasions after 28 weeks been reported (Schumacher and Schlumberger, of pregnancy in patients whose blood pressurehttp://jcp.bmj.com/ 1963; Schultze and Schwick, 1959). We therefore was less than 140/90 m-m Hg in the first trimester. thought it would be of interest to determine the Most of the patients had oedema. Preeclampsia serum oI2-macroglobulin levels in preeclampsia, a with proteinuria was diagnosed when proteinuria complication of pregnancy which bears a certain was detected for the first time after 28 weeks of similarity to the nephrotic syndrome.
    [Show full text]
  • Weakness of Biochemical Markers of Nutritional and Inflammatory Status
    European Journal of Clinical Nutrition (1997) 51, 148±153 ß 1997 Stockton Press. All rights reserved 0954±3007/97 $12.00 Weakness of biochemical markers of nutritional and in¯ammatory status as prognostic indices for growth retardation and morbidity of young children in central Africa R Tonglet1,4, E Mahangaiko Lembo2,4, M Dramaix3 and P Hennart3,4 1School of Public Health, Faculty of Medicine, Catholic University of Louvain, Brussels, Belgium; 2Rural Health District of Kirotshe, Goma, Northern Kivu, Zaire; 3School of Public Health, Faculty of Medicine, Free University of Brussels, Brussels, Belgium; and 4Centre Scienti®que et MeÂdical de l'Universite Libre de Bruxelles pour ses ActiviteÂs de CoopeÂration (CEMUBAC), Brussels, Belgium Objective: To determine to what extent biochemical markers of the nutritional and in¯ammatory status of young children are related to subsequent growth retardation and morbidity. Design: Population-based follow-up study of a cohort of children from admission to ®nal survey round six months later. Setting: Health area in Northern Kivu, Zaire. Subjects: 842 children under two years of age of whom about one-third gave informed consent to capillary blood collection. Main outcome measures: Concentration of albumin, transferrin, transthyretin, a1-acid glycoprotein, C-reactive protein, and complement component C3 at baseline, and three and six months later. Incremental growth per 1 month, 3 months and 6 months of follow-up. Cumulative incidence of disease per 1 month and 3 months interval. Results: A high proportion of children was with low concentrations of transport proteins and high concentrations of acute-phase reactants. Weight growth and arm circumference growth did not vary signi®cantly with respect to initial concentrations of biomarkers, but subsequent height growth was lower in children with high values of transferrin, a1-acid glycoprotein, and complement component C3 at baseline.
    [Show full text]
  • Transferrin Plays a Central Role in Coagulation Balance by Interacting with Clotting Factors
    www.nature.com/cr www.cell-research.com ARTICLE OPEN Transferrin plays a central role in coagulation balance by interacting with clotting factors Xiaopeng Tang1,2, Zhiye Zhang1, Mingqian Fang1,2, Yajun Han1, Gan Wang1, Sheng Wang3, Min Xue1,2, Yaxiong Li4, Li Zhang4, Jian Wu4, Biqing Yang5, James Mwangi1,2, Qiumin Lu1, Xiaoping Du6 and Ren Lai1,7,8,9,10 Coagulation balance is maintained through fine-tuned interactions among clotting factors, whose physiological concentrations vary substantially. In particular, the concentrations of coagulation proteases (pM to nM) are much lower than their natural inactivator antithrombin (AT, ~ 3 μM), suggesting the existence of other coordinators. In the current study, we found that transferrin (normal plasma concentration ~40 μM) interacts with fibrinogen, thrombin, factor XIIa (FXIIa), and AT with different affinity to maintain coagulation balance. Normally, transferrin is sequestered by binding with fibrinogen (normal plasma concentration ~10 μM) at a molar ratio of 4:1. In atherosclerosis, abnormally up-regulated transferrin interacts with and potentiates thrombin/FXIIa and blocks AT’s inactivation effect on coagulation proteases by binding to AT, thus inducing hypercoagulability. In the mouse model, transferrin overexpression aggravated atherosclerosis, whereas transferrin inhibition via shRNA knockdown or treatment with anti- transferrin antibody or designed peptides interfering with transferrin-thrombin/FXIIa interactions alleviated atherosclerosis. Collectively, these findings identify that transferrin
    [Show full text]
  • Tests for the Evaluation of Preterm Labor and Premature Rupture of Membranes
    Medical Coverage Policy Effective Date ............................................. 7/15/2021 Next Review Date ....................................... 7/15/2022 Coverage Policy Number .................................. 0099 Tests for the Evaluation of Preterm Labor and Premature Rupture of Membranes Table of Contents Related Coverage Resources Overview .............................................................. 1 Recurrent Pregnancy Loss: Diagnosis and Treatment Coverage Policy ................................................... 1 Ultrasound in Pregnancy (including 3D, 4D and 5D General Background ............................................ 2 Ultrasound) Medicare Coverage Determinations .................. 13 Coding/Billing Information .................................. 13 References ........................................................ 15 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ
    [Show full text]
  • Neoplastic Transformation Inactivates Specific Trans-Acting Factor(S
    Proc. Nati. Acad. Sci. USA Vol. 85, pp. 1744-1748, March 1988 Biochemistry Neoplastic transformation inactivates specific trans-acting factor(s) required for the expression of the thyroglobulin gene (differentiation/DNA-protein interaction/thyroglobufln) V. ENRICO AVVEDIMENTO*tt, ANNAMARIA MUSTI*, ALFREDO Fusco*, MARCO J. BONAPACE*, AND ROBERTO Di LAURO§¶ *Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerce, Dipartimento di Biologia e Patologia Molecolare, II Facolta di Medicina e Chirurgia, Universita di Napoli, Naples, Italy; and fLaboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Communicated by Maxine F. Singer, October 5, 1987 (receivedfor review February 18, 1987) ABSTRACT The expression of rat thyroglobulin gene is sible for the block of the thyroglobulin expression in trans- repressed following the transformation ofrat thyroid cells with formed thyroid cells. Kirsten murine sarcoma virus. The expression of a reporter We report here data on the expression of the reporter gene gene fused to the thyroglobulin promoter is down-regulated in for chloramphenicol acetyl transferase fused to the Tg pro- transformed thyroid cells in transient or in stable transfection moter, designated Tg P-CAT gene, in transformed cells assays. DNase and exonuclease HI cleavage-protection analysis either in transient or in stable transfection assays. We show: reveals that a promoter binding activity located at -60 base (i) that this marker is down-regulated in transformed thyroid pairs from the transcription start site is substantially reduced cells; (ii) that a specific Tg promoter binding activity is in transformed thyroid cells. The repression in the trans- substantially reduced upon transformation; and (iii) that the formed cells of the reporter gene joined to the thyroglobulin Tg P-CAT gene in transformed cells can be reactivated by promoter can be reversed by fusion with normal differentiated fusion with a normal differentiated thyroid cell.
    [Show full text]
  • Intradiscal Injection of an Autologous Alpha-2-Macroglobulin (A2M) Concentrate Alleviates Back Pain in FAC-Positive Patients
    Orthopedics and Rheumatology Open Access Journal ISSN: 2471-6804 Research Article Ortho & Rheum Open Access Volume 4 Issue 2 - January 2017 Copyright © All rights are reserved by Pasquale X Montesano MD DOI: 10.19080/OROAJ.2017.04.555634 Intradiscal Injection of an Autologous Alpha-2- Macroglobulin (A2M) Concentrate Alleviates Back Pain in FAC-Positive Patients Pasquale X Montesano MD, *Jason M Cuellar MD, PhD, Gaetano J Scuderi MD 1Spine Surgeon, Montesano Spine and Sport, USA 2Spine surgeon, Department of Orthopaedic Surgery, Cedars-Sinai Medical Center, USA 3Spine surgeon, USA Submission: December 14, 2016; Published: January 03, 2017 *Corresponding author: Tel: ; Email: Jason M. Cuéllar MD, PhD, 450 N. Roxbury Drive, 3rd floor, Beverly Hills, CA 90210, Abstract Objectives: A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been identified in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can prevent the formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3 complex and therefore may be an efficacious treatment. The present study was designed to determine a.b. The ability of autologousFAC to predict concentrated the response A2M to tothis relieve biologic back therapy. pain in patients with LBP from DDD and Study design/setting: Prospective cohort Patients: Main Outcome 24 patients Measurements: with low back pain and MRI-concordant DDD Oswestry disability index (ODI) and visual analog scores (VAS) were noted at baseline and at 3- and 6-month follow-up.Methods: Primary outcome of clinical improvement was defined as patients with both a decrease in VAS of at least 3 points and ODI >20 points.
    [Show full text]
  • A Deficiency in Golgi Localised N-Acetyl-Glucosaminyltransferase II 125
    Archives of Disease in Childhood 1994; 71: 123-127 123 Carbohydrate deficient glycoprotein syndrome type II: a deficiency in Golgi localised Arch Dis Child: first published as 10.1136/adc.71.2.123 on 1 August 1994. Downloaded from N-acetyl-glucosaminyltransferase II J Jaeken, H Schachter, H Carchon, P De Cock, B Coddeville, G Spik Abstract Case report The carbohydrate deficient glycoprotein The patient, a Belgian boy, was born in 1983 (CDG) syndromes are a family of genetic after a normal pregnancy and delivery. His multisystemic disorders with severe birth weight was 3250 g, length 50 cm, and nervous system involvement. This report head circumference 35 cm. He had a younger is on a child with a CDG syndrome that healthy brother; the parents were not related. differs from the classical picture but is The father's height was on the 3rd centile and very similar to a patient reported in head circumference on the 90th centile; he 1991. Both these patients are therefore showed some facial dysmorphism with a short designated CDG syndrome type II. neck but was otherwise normal. From birth Compared with type I patients they have the patient was hypotonic. He showed a more severe psychomotor retardation dysmorphic features: a hook nose, large but no peripheral neuropathy nor cere- dysplastic ears in oblique position, thin lips, bellar hypoplasia. The serum transferrin prognathia of the maxilla, short neck, isoform pattern obtained by isoelec- proximal implantation of the thumbs, and tric focusing showed disialotransferrin irregular position of the toes. There was a as the major fraction. The serum cardiac murmur due to a small ventricular disialotransferrin, studied in the present septal defect.
    [Show full text]
  • The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice
    International Journal of Molecular Sciences Article The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice Beáta Róka 1,Pál Tod 1,2, Tamás Kaucsár 1, Matej Vizovišek 3 , Robert Vidmar 3, Boris Turk 3,4 , Marko Fonovi´c 3,4,Gábor Szénási 1 and Péter Hamar 1,2,* 1 Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; [email protected] (B.R.); [email protected] (P.T.); [email protected] (T.K.); [email protected] (G.S.) 2 Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary 3 Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia; [email protected] (M.V.); [email protected] (R.V.); [email protected] (B.T.); [email protected] (M.F.) 4 Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, 1000 Ljubljana, Slovenia * Correspondence: [email protected]; Tel.: +36-20-825-9751; Fax: +36-1-210-0100 Received: 18 November 2019; Accepted: 20 December 2019; Published: 27 December 2019 Abstract: (1) Background: Sepsis-induced acute kidney injury (AKI) is the most common form of acute kidney injury (AKI). We studied the temporal profile of the sepsis-induced renal proteome changes. (2) Methods: Male mice were injected intraperitoneally with bacterial lipopolysaccharide (LPS) or saline (control). Renal proteome was studied by LC-MS/MS (ProteomeXchange: PXD014664) at the early phase (EP, 1.5 and 6 h after 40 mg/kg LPS) and the late phase (LP, 24 and 48 h after 10 mg/kg LPS) of LPS-induced AKI.
    [Show full text]
  • Glycosylated Fibronectin As a First-Trimester Biomarker for Prediction of Gestational Diabetes
    Glycosylated Fibronectin as a First-Trimester Biomarker for Prediction of Gestational Diabetes Juha P. Rasanen, MD, PhD, Caryn K. Snyder, MPH, Paturi V. Rao, MD, PhD, Raluca Mihalache, MPHN, Seppo Heinonen, MD, PhD, Michael G. Gravett, MD, Charles T. Roberts Jr, PhD, and Srinivasa R. Nagalla, MD OBJECTIVE: To evaluate the potential clinical utility of and placental lactogen were significantly associated serum biomarkers for first-trimester prediction of gesta- (P,.001) with GDM. After adjustment for maternal fac- tional diabetes mellitus (GDM). tors and other biomarkers, glycosylated fibronectin dem- METHODS: Maternal serum concentrations of glycosy- onstrated an independent association with GDM , lated (Sambucus nigra lectin–reactive) fibronectin, adipo- (P .001). Adiponectin, high-sensitivity CRP, and placental nectin, sex hormone–binding globulin, placental lactogen, lactogen demonstrated modest classification perfor- and high-sensitivity C-reactive protein (CRP) were mea- mance compared with glycosylated fibronectin (respec- sured at 5–13 weeks of gestation in a case-control study of tively: area under the curve [AUC] 0.63; 95% confidence 90 pregnant women with subsequent development of interval [CI] 0.53–0.71; AUC 0.68; 95% CI 0.60–0.76; and GDM and in 92 control group participants. Ability to AUC 0.67, 95% CI 0.59–0.75; compared with AUC 0.91; detect GDM was assessed using logistic regression mod- 95% CI 0.87–0.96). Glycosylated fibronectin levels above eling and receiver operating characteristic (ROC) curves. a threshold of 120 mg/L correctly identified 57 GDM case Classification performance and positive and negative pre- group participants with a positive predictive value of dictive values were reported at specific thresholds.
    [Show full text]
  • Alpha-1-Antitrypsin Phenotypes in Patients with Renal Arterial Fibromuscular Dysplasia
    Journal of Human Hypertension (2000) 14, 91–94 2000 Macmillan Publishers Ltd All rights reserved 0950-9240/00 $15.00 www.nature.com/jhh ORIGINAL ARTICLE Alpha-1-antitrypsin phenotypes in patients with renal arterial fibromuscular dysplasia A Bofinger, C Hawley, P Fisher, N Daunt, M Stowasser and R Gordon Hypertension Unit, University of Queensland Department of Medicine, Greenslopes Private Hospital, Brisbane, Queensland, Australia ␣ Fibromuscular dysplasia (FMD) is a significant cause of one (1.2%) PiSZ), suggesting that 1-AT deficiency is renal artery stenosis, especially in young females. A not a common aetiological factor in renal arterial FMD. ␣ ␣ rare association between FMD and 1-antitrypsin ( 1- However, despite FMD being three times less common ␣ AT) deficiency has been reported. We compared the 1- in males than females, and carotid artery dissection AT phenotype distribution in 83 patients with renal being a rare occurrence, a male with PiMS deficiency arterial FMD with those published for Australian popu- phenotype presented with internal carotid artery dissec- ␣ lations. 1-AT phenotyping was performed by isoelectric tion and had bilateral renal artery FMD. Further, a patient focusing between pH 4.2 and pH 4.9 on polyacrylamide with PiSZ deficiency phenotype was one of two sisters gels with PiM1M2, PiFM (non-deficiency alleles), PiMS with FMD and was more severely affected than her PiMM and PiMZ (deficiency alleles) markers. Following pheno- normal phenotype sibling. These two patients from the ␣ typing, 1-AT genotyping was performed in 10 patients present series together with nine culled from the litera- ␣ to confirm the presence of S and/or Z alleles.
    [Show full text]