Science.gov

Sample records for acute phase serum

  1. Serum Profiling of Rat Dermal Exposure to JP-8 Fuel Reveals an Acute-Phase Response.

    PubMed

    Larabee, Jason L; Hocker, James R; Cheung, John Y; Gallucci, Randle M; Hanas, Jay S

    2008-01-01

    ABSTRACT Dermal exposure to JP-8 petroleum jet fuel leads to toxicological responses in humans and rodents. Serum profiling is a molecular analysis of changes in the levels of serum proteins and other molecules in response to changes in physiology. This present study utilizes serum profiling approaches to examine biomolecular changes in the sera of rats exposed to dermal applications of JP-8 (jet propulsion fuel-8). Using gel electrophoresis and electrospray ionization (ESI) mass spectrometry (MS), levels of serum proteins as well as low-mass constituents were found to change after dermal exposures to JP-8. The serum protein levels altered included the acute-phase response proteins haptoglobin, ceruloplasmin, alpha(1)-inhibitor III, and apolipoprotein A-IV. Haptoglobin levels increased after a 1-day JP-8 dermal exposure and continued to increase through 7 days of exposure. Ceruloplasmin levels increased after 5 days of exposure. Serum alpha(1)-inhibitor III was reduced after a 1-day exposure and the depletion continued after 7 days of exposure. Apolipoprotein A-IV increased after a 1-day exposure and then returned to basal levels after 3- and 5-day exposures of JP-8. Levels of the acute-phase protein alpha(2)-macroglobulin were found to not vary over these time course studies. Using ESI-MS analysis directly on the sera from rats exposed to dermal JP-8, low-mass sera constituents were found to correlate with control (acetone) or JP-8 exposure. PMID:20020890

  2. Two major ruminant acute phase proteins, haptoglobin and serum amyloid A, as serum biomarkers during active sheep scab infestation

    PubMed Central

    2013-01-01

    Two ruminant acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were evaluated as serum biomarkers (BMs) for sheep scab–a highly contagious ectoparasitic disease caused by the mite Psoroptes ovis, which is a major welfare and production threat worldwide. The levels of both APPs increased in serum following experimental infestation of sheep with P. ovis, becoming statistically significantly elevated from pre-infestation levels at 4 weeks post-infestation. Following successful treatment of infested sheep with an endectocide, Hp and SAA serum levels declined rapidly, with half lives of less than 3 days. In contrast, serum IgG levels which specifically bound the P. ovis-derived diagnostic antigen Pso o 2 had a half-life of 56 days. Taking into account pre-infestation serum levels, rapidity of response to infestation and test sensitivity at the estimated optimum cut-off values, SAA was the more discriminatory marker. These studies illustrated the potential of SAA and Hp to indicate current sheep scab infestation status and to augment the existing Pso o 2 serological assay to give disease-specific indications of both infestation and successful treatment. PMID:24176040

  3. The Acute-Phase Proteins Serum Amyloid A and C Reactive Protein in Transudates and Exudates

    PubMed Central

    Okino, Alessandra M.; Bürger, Cristiani; Cardoso, Jefferson R.; Lavado, Edson L.; Lotufo, Paulo A.; Campa, Ana

    2006-01-01

    The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10 ± 0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39 ± 0.37 and 0.68 ± 0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r = 0.764;p < 0.0001). The concentration of SAA in transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8–360.5 g/mL). SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates. PMID:16864904

  4. Acute phase proteins in serum and cerebrospinal fluid in the course of bacterial meningitis.

    PubMed

    Paradowski, M; Lobos, M; Kuydowicz, J; Krakowiak, M; Kubasiewicz-Ujma, B

    1995-08-01

    We carried out estimations of the following acute phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and viral meningitis (VM, n = 30). We have shown that determinations of concentrations of AAG and CRP in serum and CER in CSF are useful in differentiation between BM and VM. The diagnostic power of these three tests (the areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is bigger, though statistically not significantly, than that of traditional parameters of BM in CSF, i.e., total protein concentration and white blood cell count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring marker in the course of BM treatment. Convenience of serum sampling constitutes an advantage over traditional BM parameters in CSF. PMID:8521602

  5. Serum protein capillary electrophoresis and measurement of acute phase proteins in a captive cheetah (Acinonyx jubatus) population.

    PubMed

    Depauw, Sarah; Delanghe, Joris; Whitehouse-Tedd, Katherine; Kjelgaard-Hansen, Mads; Christensen, Michelle; Hesta, Myriam; Tugirimana, Pierrot; Budd, Jane; Dermauw, Veronique; Janssens, Geert P J

    2014-09-01

    Renal and gastrointestinal pathologies are widespread in the captive cheetah (Acinonyx jubatus) population but are often diagnosed at a late stage, because diagnostic tools are limited to the evaluation of clinical signs or general blood examination. Presently, no data are available on serum proteins and acute-phase proteins in cheetahs during health or disease, although they might be important to improve health monitoring. This study aimed to quantify serum proteins by capillary electrophoresis in 80 serum samples from captive cheetahs, categorized according to health status and disease type. Moreover, serum amyloid A concentrations were measured via a turbidimetric immunoassay validated in domestic cats, whereas haptoglobin and C-reactive protein were determined by non-species-specific functional tests. Cheetahs classified as healthy had serum protein and acute phase protein concentrations within reference ranges for healthy domestic cats. In contrast, unhealthy cheetahs had higher (P < 0.001) serum amyloid A, alpha2-globulin, and haptoglobin concentrations compared with the healthy subgroup. Moreover, serum amyloid A (P = 0.020), alpha2-globulin (P < 0.001) and haptoglobin (P = 0.001) concentrations in cheetahs suffering from chronic kidney disease were significantly greater compared to the reportedly healthy cheetahs. Our study indicates that serum proteins in the cheetah can be analyzed by routine capillary electrophoresis, whereas acute-phase proteins can be measured using available immunoassays or non-species-specific techniques, which are also likely to be applicable in other exotic felids. Moreover, results suggest that serum amyloid A and haptoglobin are important acute-phase proteins in the diseased cheetah and highlight the need to evaluate their role as early-onset markers for disease. PMID:25314816

  6. Impact of individual acute phase serum amyloid A isoforms on HDL metabolism in mice.

    PubMed

    Kim, Myung-Hee; de Beer, Maria C; Wroblewski, Joanne M; Charnigo, Richard J; Ji, Ailing; Webb, Nancy R; de Beer, Frederick C; van der Westhuyzen, Deneys R

    2016-06-01

    The acute phase (AP) reactant serum amyloid A (SAA), an HDL apolipoprotein, exhibits pro-inflammatory activities, but its physiological function(s) are poorly understood. Functional differences between SAA1.1 and SAA2.1, the two major SAA isoforms, are unclear. Mice deficient in either isoform were used to investigate plasma isoform effects on HDL structure, composition, and apolipoprotein catabolism. Lack of either isoform did not affect the size of HDL, normally enlarged in the AP, and did not significantly change HDL composition. Plasma clearance rates of HDL apolipoproteins were determined using native HDL particles. The fractional clearance rates (FCRs) of apoA-I, apoA-II, and SAA were distinct, indicating that HDL is not cleared as intact particles. The FCRs of SAA1.1 and SAA2.1 in AP mice were similar, suggesting that the selective deposition of SAA1.1 in amyloid plaques is not associated with a difference in the rates of plasma clearance of the isoforms. Although the clearance rate of SAA was reduced in the absence of the HDL receptor, scavenger receptor class B type I (SR-BI), it remained significantly faster compared with that of apoA-I and apoA-II, indicating a relatively minor role of SR-BI in SAA's rapid clearance. These studies enhance our understanding of SAA metabolism and SAA's effects on AP-HDL composition and catabolism. PMID:27018443

  7. Serum amyloid A in marine bivalves: An acute phase and innate immunity protein.

    PubMed

    Rosani, U; Domeneghetti, S; Gerdol, M; Franzoi, M; Pallavicini, A; Venier, P

    2016-06-01

    Serum amyloid A (SAA) is among the most potent acute phase proteins (APP) in vertebrates. After injury, its early expression can dramatically increase to promote the recruitment of immuno-competent cells, expression of pro-inflammatory proteins and the activation of the innate immune defences. Although APP have been studied in many vertebrates, only recently their search was extended to invertebrates and the finding of SAA-like molecules has opened new questions on the immune-regulatory functions of these soluble proteins in the animal kingdom. Taking advantage of the considerable amount of genomic and transcriptomic data currently available, we retrieved 51 SAA-like proteins in several protostome taxa comprising 21 marine bivalve species and basal metazoans. In addition to vertebrate-like SAAs, we identified a second protein type with peculiar features. In the bivalves Crassostrea gigas and Mytilus galloprovincialis, both digital expression analysis and qPCR data indicated an induction of the classical SAA after bacterial challenge. PMID:26828389

  8. Influence of racing on the serum concentrations of acute-phase proteins and bone metabolism biomarkers in racing greyhounds.

    PubMed

    Tharwat, M; Al-Sobayil, F; Buczinski, S

    2014-11-01

    This study was designed to evaluate the influence of racing on the serum concentrations of the acute-phase proteins (APPs) C-reactive protein (CRP), haptoglobin (Hp) and serum amyloid A (SAA) in 32 endurance-racing greyhounds. The study also aimed to investigate the effect of a 7 km race on the bone biomarkers osteocalcin (OC), bone-specific alkaline phosphatase (b-ALP) and pyridinoline cross-links (PYD). Total white blood cell (WBC) count, and the serum concentrations of cortisol, tumour necrosis factor-α (TNF-α), vitamin D and testosterone were also determined. Blood samples were collected 24 h prior to (T0) and within 2 h of completion of the race (T1). Compared to baseline values, WBC count did not change significantly (P = 0.2300), serum cortisol, Hp and SAA increased, while TNF-α and CRP decreased (P <0.0001 for each). There were no significant differences between the pre- and post-race serum concentrations of OC and PYD (P = 0.9500 and P = 0.2600, respectively), but serum b-ALP increased significantly (P = 0.0004). Serum concentrations of vitamin D and testosterone increased after racing (P = 0.0100 and P <0.0001, respectively). In this study, a 7 km race stimulated an acute-phase response, demonstrated by significant increases in the serum concentrations Hp and SAA in racing greyhounds. Increased serum b-ALP post-race probably indicates a change in bone metabolism and deserves further study. PMID:25294662

  9. Regulation of serum amyloid A protein expression during the acute-phase response.

    PubMed Central

    Jensen, L E; Whitehead, A S

    1998-01-01

    The acute-phase (AP) serum amyloid A proteins (A-SAA) are multifunctional apolipoproteins which are involved in cholesterol transport and metabolism, and in modulating numerous immunological responses during inflammation and the AP response to infection, trauma or stress. During the AP response the hepatic biosynthesis of A-SAA is up-regulated by pro-inflammatory cytokines, and circulating concentrations can increase by up to 1000-fold. Chronically elevated A-SAA concentrations are a prerequisite for the pathogenesis of secondary amyloidosis, a progressive and fatal disease characterized by the deposition in major organs of insoluble plaques composed principally of proteolytically cleaved A-SAA, and may also contribute to physiological processes that lead to atherosclerosis. There is therefore a requirement for both positive and negative control mechanisms that permit the rapid induction of A-SAA expression until it has fulfilled its host-protective function(s) and subsequently ensure that its expression can be rapidly returned to baseline. These mechanisms include modulation of promoter activity involving, for example, the inducer nuclear factor kappaB (NF-kappaB) and its inhibitor IkappaB, up-regulatory transcription factors of the nuclear factor for interleukin-6 (NF-IL6) family and transcriptional repressors such as yin and yang 1 (YY1). Post-transcriptional modulation involving changes in mRNA stability and translation efficiency permit further up- and down-regulatory control of A-SAA protein synthesis to be achieved. In the later stages of the AP response, A-SAA expression is effectively down-regulated via the increased production of cytokine antagonists such as the interleukin-1 receptor antagonist (IL-1Ra) and of soluble cytokine receptors, resulting in less signal transduction driven by pro-inflammatory cytokines. PMID:9729453

  10. Serum retinol is associated with stage of pregnancy and the acute phase response in pregnant women in Guinea-Bissau.

    PubMed

    Kæstel, Pernille; Martinussen, Torben; Aaby, Peter; Michaelsen, Kim F; Friis, Henrik

    2012-05-01

    Vitamin A deficiencies in pregnancy may impair the health of the mother and the growth, development, and later health of her offspring. However, the understanding of the variability of micronutrient status markers during pregnancy is limited. We measured serum retinol and β-carotene and the acute phase proteins C-reactive protein (CRP) and α(1)-antichymotrypsin (ACT) in 738 pregnant women in a cross-sectional study in Guinea-Bissau, West Africa. Gestational age ranged from 7 to 42 wk (mean ± SD = 23 ± 7 wk). The serum retinol concentration was 1.03 ± 0.33 μmol/L (mean ± SD) whereas serum β-carotene was 1.40 (0.85, 2.13) μmol/L [median (25, 75 percentile)]. Vitamin A deficiency (serum retinol <0.70 μmol/L) was observed in 13.8% of individuals. Serum CRP was elevated (>3 mg/L) in 51.6% of individuals and ACT (>0.3 g/L) in 66.3%. Gestational age >20 wk (β = -0.11; P < 0.001) as well as elevated serum CRP (β = -0.16; P < 0.001) and ACT (β = -0.80; P = 0.004) were associated with lower serum retinol. Based on this large cross-sectional study, we suggest that serum retinol and its conventional cutoff may be underestimating the vitamin A status in late pregnancy and in populations with high prevalence of infections. However, prospective cohort studies measuring the serum concentration of retinol during and after pregnancy and inflammation are needed to describe the physiological behavior of serum retinol and thereby to improve the assessment of vitamin A status. PMID:22437561

  11. The acute phase protein serum amyloid A (SAA) as an inflammatory marker in equine influenza virus infection.

    PubMed

    Hultén, C; Sandgren, B; Skiöldebrand, E; Klingeborn, B; Marhaug, G; Forsberg, M

    1999-01-01

    The acute phase protein serum amyloid A (SAA) has proven potentially useful as an inflammatory marker in the horse, but the knowledge of SAA responses in viral diseases is limited. The aim of this study was to evaluate SAA as a marker for acute equine influenza A2 (H3N8) virus infection. This is a highly contagious, serious condition that inflicts suffering on affected horses and predisposes them to secondary bacterial infections and impaired performance. Seventy horses, suffering from equine influenza, as verified by clinical signs and seroconversion, were sampled in the acute (the first 48 h) and convalescent (days 11-22) stages of the disease, and SAA concentrations were determined. Clinical signs and rectal temperature were recorded. Secondary infections, that could have influenced SAA concentrations, were clinically suspected in 4 horses. SAA concentrations were higher in the acute stage than in the convalescent stage, and there was a statistically positive relationship between acute stage SAA concentrations and clinical signs and between acute stage SAA concentrations and maximal rectal temperature. Horses sampled early in the acute stage had lower SAA concentrations than those sampled later, indicating increasing concentrations during the first 48 h. There was a statistically positive relationship between convalescent SAA concentrations and degree of clinical signs during the disease process. The results of this investigation indicate that equine SAA responds to equine influenza infection by increasing in concentration during the first 48 h of clinical signs and returning to baseline within 11-22 days in uncomplicated cases. PMID:10918902

  12. Acute phase reaction and acute phase proteins*

    PubMed Central

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337

  13. Is the serum amyloid A protein in acute phase plasma high density lipoprotein the precursor of AA amyloid fibrils?

    PubMed Central

    Baltz, M L; Rowe, I F; Caspi, D; Turnell, W G; Pepys, M B

    1986-01-01

    Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is generally considered to be the precursor of AA protein, which forms the fibrils in reactive systemic amyloidosis in man and animals. This view is based on amino acid sequence identity between AA and the amino-terminal portion of SAA. However, in extensive and well-controlled studies of experimentally induced murine AA amyloidosis, we were unable to demonstrate a direct precursor-product relationship between SAA, in SAA-rich HDL preparations from acute phase or amyloidotic mouse or human serum, and AA protein in the amyloid deposits. This raises the possibility that SAA in its usual form, as an apolipoprotein of HDL synthesized during the acute phase response, may not be the major precursor of AA fibrils. The amyloidogenic forms of circulating SAA molecules may not be isolated during the preparation of HDL. Alternatively, particularly in the light of recent evidence that SAA mRNA is expressed in many different tissues throughout the body of appropriately stimulated animals, amyloidogenic SAA may be derived from sources other than the liver cells in which SAA-rich HDL is synthesized. PMID:3105937

  14. Differential plasma clearance of murine acute-phase serum amyloid A proteins SAA1 and SAA2.

    PubMed Central

    Kluve-Beckerman, B; Yamada, T; Hardwick, J; Liepnieks, J J; Benson, M D

    1997-01-01

    Serum amyloid A (SAA) proteins SAA1 and SAA2 are prominent acute-phase reactants which circulate in association with the high-density-lipoprotein (HDL) fraction of plasma. Plasma levels of SAA1 and SAA2 increase dramatically, by as much as 1000-fold, within 24 h of tissue injury and then rapidly decrease with cessation of the inflammatory stimulus, suggesting that SAA clearance and/or catabolism is important to the re-establishment of homoeostasis. In this context, aberrant SAA catabolism has long been considered a potential factor in the pathogenesis of reactive amyloidosis. To initiate studies aimed at understanding the differential regulation of SAA metabolism, we have produced 35S-labelled murine SAA1 and SAA2 in Escherichia coli, bound them individually to HDL, and then compared the plasma-clearance characteristics of SAA1 and SAA2 under normal and acute-phase conditions. When bound to normal HDL, SAA2 [half-life (t1/2) = 30 min] was cleared significantly faster than SAA1 (t1/2 = 75 min). Clearance of SAA1 and SAA2 was significantly slower when each was bound to acute-phase HDL as opposed to normal HDL, when clearance rates were determined in acute-phase mice versus normal mice, and when normal HDL was remodelled to contain both recombinant isotypes rather than just one of the isotypes. Thus it appears that an increased amount of SAA on HDL, or possibly the combined presence of both isotypes on HDL, is associated with a prolongation in the plasma half-life of SAA. PMID:9065791

  15. Investigation of the solubility and the potentials for purification of serum amyloid A (SAA) from equine acute phase serum – a pilot study

    PubMed Central

    2013-01-01

    Background Serum amyloid A (SAA) is useful as a diagnostic marker of systemic inflammation in horses, but only heterologous assays based on non-equine calibration and standardization are available for measurements of equine SAA. More accurate measurements could be obtained using purified species-specific SAA in native conformation for assay calibration and standardization. Further knowledge about the biochemical properties of SAA would facilitate a future production of native species-specific calibration material Therefore, the aim of the study was an investigation of the solubility and potentials for purification of equine SAA based on biochemical properties. Freeze dried equine acute phase serum was dissolved in 70% 2-propanol, 8 M urea, and milli-Q water, respectively. Supercritical fluid extraction (SFE), size-exclusive chromatography (FPLC-SEC), and preparative isoelectric focusing (IEF) were performed in the attempt to purify. Immunostaining of IEF blots were used for isoform-specific detection of SAA in the preparations and purity was assessed by silverstained SDS-PAGE. Findings SAA was soluble in 70% 2-propanol, 8 M urea and Milli-Q water. SAA was not separated in the lipophilic or ampipathic fractions following SFE. SAA was included in a FPLC-SEC-fraction of 237 kDa, despite the molecular weight known to be much smaller, suggesting binding to other serum constituents. SAA precipitated following separation of other serum proteins by preparative IEF. Discussion No effective purification of SAA was achieved in the present study, but findings important for future investigations were made. The study suggested that SAA is not exclusively hydrophobic, but appears less hydrophobic when interacting with other serum components. These results suggest more complex aspects of solubility than previously believed, and indicate potentials for purification of native SAA. PMID:23590853

  16. The Acute Phase Protein Serum Amyloid A Induces Lipolysis and Inflammation in Human Adipocytes through Distinct Pathways

    PubMed Central

    Faty, Aurélie; Ferré, Pascal; Commans, Stéphane

    2012-01-01

    Background The acute phase response (APR) is characterized by alterations in lipid and glucose metabolism leading to an increased delivery of energy substrates. In adipocytes, there is a coordinated decrease in Free Fatty acids (FFAs) and glucose storage, in addition to an increase in FFAs mobilization. Serum Amyloid A (SAA) is an acute phase protein mainly associated with High Density Lipoproteins (HDL). We hypothesized that enrichment of HDL with SAA, during the APR, could be implicated in the metabolic changes occurring in adipocytes. Methodology/Principal Findings In vitro differentiated human adipocytes (hMADS) were treated with SAA enriched HDL or recombinant SAA and the metabolic phenotype of the cells analyzed. In hMADS, SAA induces an increased lipolysis through an ERK dependent pathway. At the molecular level, SAA represses PPARγ2, C/EBPα and SREBP-1c gene expression, three transcription factors involved in adipocyte differentiation or lipid synthesis. In addition, the activation of the NF-κB pathway by SAA leads to the induction of pro-inflammatory cytokines and chemokines, as in the case of immune cells. These latter findings were replicated in freshly isolated mature human adipocytes. Conclusions/Significance Besides its well-characterized role in cholesterol metabolism, SAA has direct metabolic effects on human adipocytes. These metabolic changes could be at least partly responsible for alterations of adipocyte metabolism observed during the APR as well as during pathophysiological conditions such as obesity and conditions leading to insulin resistant states. PMID:22532826

  17. Serum levels of acute phase proteins: SAA, Hp and progesterone (P4) in mares with early embryonic death.

    PubMed

    Krakowski, L; Krawczyk, C H; Kostro, K; Stefaniak, T; Novotny, F; Obara, J

    2011-08-01

    The study involved 46 healthy purebred Arabian mares exhibiting regular oestrous cycles that underwent artificial insemination (AI). Pregnancy was detected ultrasonographically (US) in 40 mares. In 15 mares in foal, early embryonic death (EED) was observed during the pregnancy days 14-21. Blood for determinations of serum acute phase proteins (SAA and Hp) and progesterone (P4) was sampled 12-24 h before ovulation and the first insemination, at 12, 24, 72, 96 h and on day 7, 10, 14, 21, 35 and 55 after ovulation. The results revealed that in 25 mares without EED, the serum levels of P4, SAA and Hp were within physiological limits; in 15 mares with EED, the levels of SAA and Hp were significantly increased. In seven mares with EED, high levels of SAA and Hp were already found before ovulation and at 12, 24, 72, 96 h as well as on day 7 and 10 post-ovulation, whereas the level of P4 was normal for early pregnancy. In the remaining eight mares with EED, increased levels of SAA and Hp were found at 72 h after ovulation and maintained until day 55. In this group, the level of P4 decreased since 96 h after ovulation. Determinations of SAA, Hp and P4 in mares in early pregnancy (EP) are useful for monitoring normal development of pregnancy and for diagnosis of subclinical genital inflammations, which may lead to EED. PMID:21241377

  18. Development & evaluation of biotinylated DNA probe for clinical diagnosis of chikungunya infection in patients’ acute phase serum & CSF samples

    PubMed Central

    Kumar, Jyoti S.; Parida, Manmohan; Lakshmana Rao, P.V.

    2013-01-01

    Background & objectives: The resurgence of chikungunya virus (CHIKV) in the Indian Ocean Islands and India has drawn worldwide attention due to its explosive nature, high morbidity and complex clinico-pathological manifestations. The early confirmatory diagnosis of CHIKV is essential for management as well as control of unprecedented epidemics. The present study describes the development and evaluation of a highly sensitive and specific E1 structural gene specific biotinylated DNA probe for detection of chikungunya virus in clinical samples using a dot blot format. Methods: The complementary DNA (cDNA) of CHIKV was spotted on to nylon membrane. The membrane was subjected to prehybridization and hybridization and developed using a colour development solution containing DAB chromogen. Results: The CHIKV E1 specific DNA probe was highly sensitive detecting picogram levels of target nucleic acid. The comparative evaluation with SYBR Green I based real-time RT-PCR revealed 99 per cent accordance with a sensitivity and specificity of 99 and 98 per cent, respectively. The specificity of this assay was further confirmed through cross-reaction studies with confirmed dengue and Japanese encephalitis (JE) patient serum samples along with infected culture supernatant of Ross River and Saint Louis encephalitis and plasmid DNA of O’Nyong Nyong, Semlinki forest and Sindbis viruses. Interpretation & conclusion: The DNA probe reported in this study may be useful for specific, sensitive and confirmatory clinical diagnosis of chikungunya infection in acute phase human patient serum and CSF samples. This assay can also be used in the laboratory for quantification of viral antigen in cell culture supernatant for research purpose. PMID:24056565

  19. Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis

    PubMed Central

    Thaler, Roman; Sturmlechner, Ines; Spitzer, Silvia; Riester, Scott M.; Rumpler, Monika; Zwerina, Jochen; Klaushofer, Klaus; van Wijnen, Andre J.; Varga, Franz

    2015-01-01

    Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using primary bone cells from newborn mouse calvaria. Recombinant Saa3 protein functionally inhibits osteoblast differentiation as reflected by reductions in the expression of osteoblast markers and decreased mineralization in newborn mouse calvaria. Yet, Saa3 protein enhances osteoclastogenesis in mouse macrophages/monocytes based on the number of multinucleated and tartrate-resistant alkaline phosphatase-positive cells and Calcr mRNA expression. Depletion of Saa3 in MLO osteocytes results in the loss of the mature osteocyte phenotype. Recombinant osteocalcin, which is reciprocally regulated with Saa3 at the osteoblast/osteocyte transition, attenuates Saa3 expression in MLO-Y4 osteocytes. Mechanistically, Saa3 produced by MLO-Y4 osteocytes is integrated into the extracellular matrix of MC3T3-E1 osteoblasts, where it associates with the P2 purinergic receptor P2rx7 to stimulate Mmp13 expression via the P2rx7/MAPK/ERK/activator protein 1 axis. Our data suggest that Saa3 may function as an important coupling factor in bone development and homeostasis.—Thaler, R., Sturmlechner, I., Spitzer, S., Riester, S. M., Rumpler, M., Zwerina, J., Klaushofer, K., van Wijnen, A. J., Varga, F. Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis. PMID:25491310

  20. Thermal transitions in serum amyloid A in solution and on the lipid: implications for structure and stability of acute-phase HDL.

    PubMed

    Jayaraman, Shobini; Haupt, Christian; Gursky, Olga

    2015-08-01

    Serum amyloid A (SAA) is an acute-phase protein that circulates mainly on plasma HDL. SAA interactions with its functional ligands and its pathogenic deposition in reactive amyloidosis depend, in part, on the structural disorder of this protein and its propensity to oligomerize. In vivo, SAA can displace a substantial fraction of the major HDL protein, apoA-I, and thereby influence the structural remodeling and functions of acute-phase HDL in ways that are incompletely understood. We use murine SAA1.1 to report the first structural stability study of human plasma HDL that has been enriched with SAA. Calorimetric and spectroscopic analyses of these and other SAA-lipid systems reveal two surprising findings. First, progressive displacement of the exchangeable fraction of apoA-I by SAA has little effect on the structural stability of HDL and its fusion and release of core lipids. Consequently, the major determinant for HDL stability is the nonexchangeable apoA-I. A structural model explaining this observation is proposed, which is consistent with functional studies in acute-phase HDL. Second, we report an α-helix folding/unfolding transition in SAA in the presence of lipid at near-physiological temperatures. This new transition may have potentially important implications for normal functions of SAA and its pathogenic misfolding. PMID:26022803

  1. Chicken amyloid arthropathy: serum amyloid A, interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and nitric oxide profile in acute phase (12th hour).

    PubMed

    Sevimli, A; Bülbül, T; Bülbül, A; Yagci, A

    2013-01-01

    Acute phase response (APR) is part of the early defense system, which is triggered by different stimuli including, infection, trauma, stres, inflammation and neoplasia. The APR complex is a reaction which induces homeostasis and recovery. In this research, serum amyloid A (SAA), interlaukin (IL)-1beta, IL-6, tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO) levels were measured 12 hours following injection. For this purpose, Thirty-two 5 weeks old laying chicken were allocated into four groups and intra-articular injections of Freund's adjuvant were used to induce amylod arthropathy in Groups II, III and IV. Vitamin A in group II, and methylprednisolone in group IV were added to enhance and to reduce the severity of amyloidosis, respectively. At the end of the research, it was observed that TNF-alpha and NO increased significantly (P < 0.05) in vitamin A and methylprednisolone groups whereas SAA decreased significantly (P < 0.05) in all groups. It was also observed that IL-6 increased (P < 0.05) in vitamin A group and decreased in all other gorups however, IL-1beta decreased in vitamin A and methylprednisolone groups, while it was increased in the control group. The results of this study suggest that there is a positive correlation between serum TNF-alpha levels in acute and chronic phase in chickens with amyloid arthropathy. PMID:23971191

  2. Increased serum levels of interleukin-6 and von Willenbrand Factor in early phase of acute coronary syndrome in a young and multiethnic Malaysian population

    PubMed Central

    Tiong, Wen Ni; Fong, Alan Yean Yip; Sim, Edmund Ui Hang; Chan, Hiang Chuan; Ong, Tiong Kiam; Chang, Boon Cheng; Sim, Kui Hian

    2012-01-01

    Objective Interleukin-6 (IL6; proinflammatory marker), von Willebrand Factor (vWF; endothelial dysfunction marker) and P-selectin (platelet activation marker), may play important roles in defining the pathogenesis of vulnerable plaques in acute coronary syndrome (ACS). This study aims to investigate the expression and relationship of these markers in early phases of ACS in a young and multiethnic Malaysian population. Design Peripheral whole blood mRNA, and serum levels of IL6, vWF and P-selectin were measured in 22 patients with ACS, and in 28 controls with angiographically significant coronary artery disease without previous ACS events. Venous blood from ACS patients was obtained within 1 h of hospital admission. Results No significant differences of IL6, vWF and P-selectin mRNA levels between ACS and controls were seen. ACS patients had significantly higher serum levels of IL6 and vWF (p<0.001), compared with controls. P-selectin correlated with IL6 (r=0.697, p=0.003) and vWF (r=0.497, p=0.05) at mRNA levels, indicating a possible association between these three indices of ACS pathogenesis. Conclusions Increased serum levels of IL6 and vWF suggest that inflammation and endothelial dysfunction may play a prominent role in the pathogenesis of the disease during the early phase of ACS.

  3. Deficiency of endogenous acute phase serum amyloid A protects apoE−/− mice from angiotensin II-induced abdominal aortic aneurysm formation

    PubMed Central

    Webb, NR; De Beer, MC; Wroblewski, JM; Ji, A; Bailey, W; Shridas, P; Charnigo, RJ; Noffsinger, VP; Witta, J; Howatt, DA; Balakrishnan, A; Rateri, DL; Daugherty, A; De Beer, FC

    2016-01-01

    Objective Rupture of abdominal aortic aneurysm (AAA), a major cause of death in the aged population, is characterized by vascular inflammation and matrix degradation. Serum amyloid A (SAA), an acute phase reactant linked to inflammation and matrix metalloproteinase induction, correlates with aortic dimensions before aneurysm formation in humans. We investigated whether SAA deficiency in mice impacts AAA formation during angiotensin II (AngII) infusion. Approach and Results Plasma SAA increased ~60-fold in apoE−/− mice 24 hours after i.p. AngII injection (100 μg/kg; n = 4) and ~15-fold after chronic 28-day AngII infusion (1,000 ng/kg/min; n = 9). AAA incidence and severity after 28-day AngII infusion was significantly reduced in apoE−/− mice lacking both acute phase SAA isoforms (SAAKO; n = 20) compared to apoE−/− mice (SAAWT; n = 20) as assessed by in vivo ultrasound and ex vivo morphometric analyses, despite a significant increase in systolic blood pressure in SAAKO mice compared to SAAWT mice after AngII infusion. Atherosclerotic lesion area of the aortic arch was similar in SAAKO and SAAWT mice after 28-day AngII infusion. Immunostaining detected SAA in AAA tissues of AngII-infused SAAWT mice that co-localized with macrophages, elastin breaks, and enhanced matrix metalloproteinase (MMP) activity. MMP-2 activity was significantly lower in aortas of SAAKO mice compared to SAAWT mice after 10-day AngII infusion. Conclusion Lack of endogenous acute phase SAA protects against experimental AAA through a mechanism that may involve reduced MMP-2 activity. PMID:25745063

  4. Evaluation of the systemic acute phase response and endometrial gene expression of serum amyloid A and pro- and anti-inflammatory cytokines in mares with experimentally induced endometritis.

    PubMed

    Christoffersen, Mette; Mette, Christoffersen; Baagoe, Camilla Dooleweerdt; Camilla Dooleweerdt, Baagoe; Jacobsen, Stine; Stine, Jacobsen; Bojesen, Anders Miki; Anders Miki, Bojesen; Petersen, Morten Roenn; Morten Roenn, Petersen; Lehn-Jensen, Henrik; Henrik, Lehn-Jensen

    2010-11-15

    Infectious infertility in the mare is clinically well described, little is however known about the systemic acute phase reaction (APR) and local immunological responses accompanying equine endometritis. The aim of this study was to monitor selected markers of the APR in the systemic circulation and to correlate them to the local innate immune response in the uterus during infectious endometritis. Six adult standard bred mares received an intrauterine infusion of 10(9)CFU Escherichia coli. Blood samples were obtained before (0 h) and 3, 6, 12, 24, 36, 48, 72, 96 and 120 h post inoculation (pi), and endometrial biopsies were sampled before, and 3, 12, 24, 48 and 72 h pi. The infectious endometritis elicited a systemic APR with significantly increased concentrations of the acute phase proteins (APPs) serum amyloid A (SAA) and fibrinogen. Relative gene expression analyses were performed on extracted RNA from endometrial biopsies using quantitative real-time PCR and specific primers for SAA and pro- and anti-inflammatory cytokines. Expression of SAA was significantly up-regulated at 3 and 12h pi, and a significant up-regulated expression of IL-1β, TNFα, IL-8 and IL-10 was observed at 3h pi. Plasma concentration of SAA was significantly correlated to endometrial SAA expression. The results of the present study demonstrate that endometritis gives rise to a systemic APR and an up-regulated endometrial gene expression of SAA and several pro-and anti-inflammatory cytokines. Understanding endometrial expression of acute phase proteins and selected cytokines contributing to uterine immunity in equine endometritis could improve understanding of events leading to infertility in the mare and help identify candidate genes of mediators/markers for diagnostic use. PMID:20728224

  5. Some serum acute phase proteins and immunoglobulins concentrations in calves with rotavirus, coronavirus, E. coli F5 and Eimeria species

    PubMed Central

    Balikci, E; Al, M

    2014-01-01

    The purpose of this study was to evaluate the changes in the serum concentrations of haptoglobin (Hp), serum amyloid A (SAA) and IgG, IgA in calves with diarrhea caused by rotavirus, coronavirus, Escherichia coli F5 and Eimeria species. The experiment was carried out on 40 diarrhoeic and 10 non-diarrhoeic calves (group C). A total of 13 calves were infected with rotavirus or coronavirus (group V), 12 calves with E. coli F5 (group B) and 15 calves with Eimeria species (group P). SAA and Hp levels of calves in groups V, B and P were statistically higher than group C (P<0.05). SAA and Hp levels of the group B and group P were significantly higher than the group V (P<0.05). SAA and Hp levels in group B were not significantly higher than the group P. The levels of IgG and IgA were found to be lower in groups B and V compared to other groups. There was a negative correlation between immunoglobulins and the levels of serum Hp and SAA in groups B and V (r=-0.315 and r=-0.369, respectively, P<0.05). Serum SAA, Hp, IgA and IgG levels could be useful for the diagnosis and differential diagnosis of diarrhea caused by rotavirus, coronavirus, E. coli F5 and Eimeria species. PMID:27175138

  6. Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver

    EPA Science Inventory

    Acute Phase Response (APR), a systemic reaction to infection, trauma, and inflammation, is characterized by increases and decreases in plasma levels of positive and negative acute phase proteins (APP), respectively. Although the liver has been shown to contribute to APR in variou...

  7. Molecular characterization of two immunity-related acute-phase proteins: Haptoglobin and serum amyloid A from black rockfish (Sebastes schlegeli).

    PubMed

    Jayasinghe, J D H E; Elvitigala, Don Anushka Sandaruwan; Whang, Ilson; Nam, Bo-Hye; Lee, Jehee

    2015-08-01

    Haptoglobin (Hp) and serum amyloid A (SAA) are two vital proteins involved in inflammatory reactions and are classified as acute-phase proteins. They are released from hepatocytes under inflammatory conditions to protect healthy cells from being damaged by pathogens or from self-destructive mechanisms. In this study, a previously constructed black rockfish (Sebastes schlegeli) cDNA library was used to identify the full-length cDNA sequences of Hp and SAA homologs (RfHp and RfSAA, respectively) and characterize them at the molecular level. As expected, in silico analysis of these homologs showed the typical domain architectures of their known counterparts. Open reading frames of RfHp and RfSAA consisted of 942-bp and 313-bp DNA sequences, respectively. The derived polypeptide sequence of RfHp was composed of 313 amino acids (aa) with a predicted molecular weight of 34 kD, whereas RfSAA had a 121-amino acid sequence with a molecular weight of 13 kD. Phylogenetic analysis as well as pairwise sequence alignment results showed that RfHp was more closely related to Oreochromis mossambicus from an evolutionary perspective while RfSAA was closely related to the Epinephelus coioides ortholog. Although both genes were expressed ubiquitously in the tissues analyzed, they were particularly expressed in liver tissue, suggesting their origin in hepatocytes. Quantitative real-time PCR analysis indicated that both RfHp and RfSAA were significantly up-regulated by both bacterial and viral stimulation in liver tissue, affirming their putative importance in the acute phase of first-line host immune defenses. PMID:25989623

  8. Acute-phase proteins investigation based on lectins affinity capture prior to 2-DE separation: application to serum from multiple sclerosis patients.

    PubMed

    Robotti, Andrea; Natale, Massimo; Albo, Alessandra Giuliano; Lis, Katarzyna; Perga, Simona; Marnetto, Fabiana; Gilli, Francesca; Bertolotto, Antonio

    2010-09-01

    Plasma acute-phase proteins (APPs) glyco-isoforms are important biomarkers of inflammatory processes such as those occurring in multiple sclerosis (MS). Specific analysis of these proteins is often hampered by sample biochemical complexity. The aim of our study was to set up a method to accurately visualize, identify and quantify APPs glyco-isoforms in human serum. An enrichment strategy based on affinity chromatography using the carbohydrate-binding proteins concanavalin A (ConA) and erythrina cristagalli lectin (ECL) was applied to pooled serum samples from 15 patients and 9 healthy individuals. Image analysis of 2-DE detected 30 spots with a fold change higher than 1.5. A total of 14 were statistically significant (p value<0.05): 7 up-regulated and 7 down-regulated in MS samples. ESI LC-Nanospray IT mass spectrometry analysis confirmed that all of them were APPs isoforms supporting the idea that the accurate analysis of differential glycosylation profiles in these biomarkers is instrumental to distinguish between MS patients and healthy subjects. Additionally, overlaps in ConA/ECL maps protein patterns suggest how the used lectins are able to bind sugars harbored by the same oligosaccharide structure. Among identified proteins, the presence of complex and/or hybrid type N-linked sugar structures is well known. Performing galectin-3 binding and Western blotting, we were able to demonstrate a correlation between hybrid type glyco-isoforms of β-haptoglobin and MS. In conclusion, although the patho-physiological role of the identified species still remains unclear and further validations are needed, these findings may have a relevant impact on disease-specific marker identification approaches. PMID:20715125

  9. Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis.

    PubMed

    Thaler, Roman; Sturmlechner, Ines; Spitzer, Silvia; Riester, Scott M; Rumpler, Monika; Zwerina, Jochen; Klaushofer, Klaus; van Wijnen, Andre J; Varga, Franz

    2015-04-01

    Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using primary bone cells from newborn mouse calvaria. Recombinant Saa3 protein functionally inhibits osteoblast differentiation as reflected by reductions in the expression of osteoblast markers and decreased mineralization in newborn mouse calvaria. Yet, Saa3 protein enhances osteoclastogenesis in mouse macrophages/monocytes based on the number of multinucleated and tartrate-resistant alkaline phosphatase-positive cells and Calcr mRNA expression. Depletion of Saa3 in MLO osteocytes results in the loss of the mature osteocyte phenotype. Recombinant osteocalcin, which is reciprocally regulated with Saa3 at the osteoblast/osteocyte transition, attenuates Saa3 expression in MLO-Y4 osteocytes. Mechanistically, Saa3 produced by MLO-Y4 osteocytes is integrated into the extracellular matrix of MC3T3-E1 osteoblasts, where it associates with the P2 purinergic receptor P2rx7 to stimulate Mmp13 expression via the P2rx7/MAPK/ERK/activator protein 1 axis. Our data suggest that Saa3 may function as an important coupling factor in bone development and homeostasis. PMID:25491310

  10. Serum amyloid A protein in acute viral infections.

    PubMed Central

    Miwata, H; Yamada, T; Okada, M; Kudo, T; Kimura, H; Morishima, T

    1993-01-01

    Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID:8481043

  11. Control of the Acute Phase Response

    PubMed Central

    Kushner, Irving; Broder, Martin L.; Karp, David

    1978-01-01

    In order to investigate the magnitude and kinetics of the C-reactive protein (CRP) response after differing degrees of tissue injury, we studied changes in serum concentration of this acute phase protein in 19 patients after mild or extensive acute myocardial infarction. An increase in serum CRP concentration was seen in all patients. The rate of increase in concentration was found to be exponential, with a mean hourly rate constant for the entire group of patients of 0.085 (doubling time, 8.2 h). Patients with extensive infarction attained mean serum CRP levels about 4 times as great as did patients with mild infarction. No difference could be shown in the mean rate constant between these groups, the greater CRP response in the former group resulting principally from a more protracted period of rise in serum CRP concentration. A lag period before serum CRP levels began to rise was noted in only 4 of the 13 patients in whom this could be assessed. 7 of 10 patients with presumed unstable angina (coronary insufficiency) showed no rise in CRP concentration, while a small increase as noted in 3 patients. The data suggest that acute tissue injury, such as myocardial infarction, rapidly leads to acceleration in synthesis of CRP, and that the duration of this period of acceleration is related to the extent of tissue injury. PMID:621273

  12. Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid A.

    PubMed

    Marzi, Carola; Albrecht, Eva; Hysi, Pirro G; Lagou, Vasiliki; Waldenberger, Melanie; Tönjes, Anke; Prokopenko, Inga; Heim, Katharina; Blackburn, Hannah; Ried, Janina S; Kleber, Marcus E; Mangino, Massimo; Thorand, Barbara; Peters, Annette; Hammond, Christopher J; Grallert, Harald; Boehm, Bernhard O; Kovacs, Peter; Geistlinger, Ludwig; Prokisch, Holger; Winkelmann, Bernhard R; Spector, Tim D; Wichmann, H-Erich; Stumvoll, Michael; Soranzo, Nicole; März, Winfried; Koenig, Wolfgang; Illig, Thomas; Gieger, Christian

    2010-11-01

    Elevated levels of acute-phase serum amyloid A (A-SAA) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications, type 2 diabetes, as well as various malignancies. To investigate the genetic basis of A-SAA levels, we conducted the first genome-wide association study on baseline A-SAA concentrations in three population-based studies (KORA, TwinsUK, Sorbs) and one prospective case cohort study (LURIC), including a total of 4,212 participants of European descent, and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. The region at 11p15.5-p13 (rs4150642; p = 3.20×10(-111)) contains serum amyloid A1 (SAA1) and the adjacent general transcription factor 2 H1 (GTF2H1), Hermansky-Pudlak Syndrome 5 (HPS5), lactate dehydrogenase A (LDHA), and lactate dehydrogenase C (LDHC). This region explains 10.84% of the total variation of A-SAA levels in our data, which makes up 18.37% of the total estimated heritability. The second region encloses the leptin receptor (LEPR) gene at 1p31 (rs12753193; p = 1.22×10(-11)) and has been found to be associated with CRP and fibrinogen in previous studies. Our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between A-SAA, leptin, and other acute-phase proteins. PMID:21124955

  13. Changes in serum lipid profile in the acute and convalescent Plasmodium vivax malaria: A cohort study.

    PubMed

    Mesquita, Teresinha C; Martin, Thamires G O; Alves, Eduardo R; Mello, Marcia B C; Nery, Andreia F; Gomes, Luciano T; Fontes, Cor Jesus F

    2016-11-01

    Although serum lipids are known to be altered in Plasmodium falciparum-induced malaria, little is known about such changes due to Plasmodium vivax infection. This cohort study assessed serum concentrations of triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in 164 patients in the acute phase of malaria caused by P. vivax and characterized these changes in the convalescent phase after treatment with chloroquine and primaquine. Compared to reference values, serum total cholesterol, LDL, and HDL levels were lower and triglyceride levels were higher in the acute phase. Moreover, the parasite density was negatively correlated with LDL (r=-0,189; p=0.027) and HDL (r=-0,256; p=0.001) serum levels. Eighty patients returned for clinical and laboratory revaluation 7-12days after treatment initiation. All patients showed parasite clearance and the absence of symptoms during the convalescent phase. Analysis of the serum lipids of these 80 patients showed significant increases in the serum levels of total cholesterol (p<0.0001), LDL (p<0.0001), and HDL (p<0.0001) as well as a significant reduction in triglycerides (p=0.004), indicating a trend towards a return to normal levels. This transient change in lipid profile between the acute and convalescent stages may be useful for the clinical monitoring of patients treated for vivax malaria. PMID:27461878

  14. Plasma betathromboglobulin and serum fragment E in acute partial stroke.

    PubMed

    de Boer, A C; Turpie, A G; Butt, R W; Duke, R J; Bloch, R F; Genton, E

    1982-02-01

    Plasma betathromboglobulin (BTG) and serum fragment E (FgE) were measured serially by radioimmunoassay for 7 d in 67 patients admitted with acute partial stroke. Twelve patients progressed within 7 d of admission. Plasma BTG was not different from normal in patients with acute partial stroke and did not increase significantly with stroke progression. Serum FgE was elevated in patients with acute partial stroke compared with normal values, and was significantly higher in patients who progressed compared with those who remained stable. The results indicate that fibrin formation may be more important in the process of stroke progression than activation of platelets. PMID:6174141

  15. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy

    PubMed Central

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Choudhary, M. Iqbal; Rahman, Atta-ur

    2016-01-01

    Acute leukemia is a critical neoplasm of white blood cells. In order to differentiate between the metabolic alterations associated with two subtypes of acute leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), we investigated the serum of ALL and AML patients and compared with two controls (healthy and aplastic anemia) using 1H NMR (nuclear magnetic resonance) spectroscopy. Thirty-seven putative metabolites were identified using Carr-Purcell-Meiboom-Gill (CPMG) sequence. The use of PLS-DA and OPLS-DA models gave results with 84.38% and 90.63% classification rate, respectively. The metabolites responsible for classification are mainly lipids, lactate and glucose. Compared with controls, ALL and AML patients showed serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline and fatty acid metabolisms. PMID:27480133

  16. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy.

    PubMed

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Choudhary, M Iqbal; Rahman, Atta-Ur

    2016-01-01

    Acute leukemia is a critical neoplasm of white blood cells. In order to differentiate between the metabolic alterations associated with two subtypes of acute leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), we investigated the serum of ALL and AML patients and compared with two controls (healthy and aplastic anemia) using (1)H NMR (nuclear magnetic resonance) spectroscopy. Thirty-seven putative metabolites were identified using Carr-Purcell-Meiboom-Gill (CPMG) sequence. The use of PLS-DA and OPLS-DA models gave results with 84.38% and 90.63% classification rate, respectively. The metabolites responsible for classification are mainly lipids, lactate and glucose. Compared with controls, ALL and AML patients showed serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline and fatty acid metabolisms. PMID:27480133

  17. Acute Phase Reactants as Novel Predictors of Cardiovascular Disease

    PubMed Central

    Ahmed, M. S.; Jadhav, A. B.; Hassan, A.; Meng, Qing H.

    2012-01-01

    Acute phase reaction is a systemic response which usually follows a physiological condition that takes place in the beginning of an inflammatory process. This physiological change usually lasts 1-2 days. However, the systemic acute phase response usually lasts longer. The aim of this systemic response is to restore homeostasis. These events are accompanied by upregulation of some proteins (positive acute phase reactants) and downregulation of others (negative acute phase reactants) during inflammatory reactions. Cardiovascular diseases are accompanied by the elevation of several positive acute phase reactants such as C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, white blood cell count, secretory nonpancreatic phospholipase 2-II (sPLA2-II), ferritin, and ceruloplasmin. Cardiovascular disease is also accompanied by the reduction of negative acute phase reactants such as albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, and transcortin. In this paper, we will be discussing the biological activity and diagnostic and prognostic values of acute phase reactants with cardiovascular importance. The potential therapeutic targets of these reactants will be also discussed. PMID:24049653

  18. Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

    PubMed

    Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

    2015-01-01

    Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD. PMID:26447086

  19. Influence of the uterine inflammatory response after insemination with frozen-thawed semen on serum concentrations of acute phase proteins in mares.

    PubMed

    Tuppits, U; Orro, T; Einarsson, S; Kask, K; Kavak, A

    2014-05-01

    The aim of this study was to investigate the clinical relevance of measuring blood concentrations of serum amyloid A (SAA), haptoglobin (Hp) and fibrinogen (Fib) in horse reproductive management, and changes in response to artificial insemination (AI) with frozen-thawed semen. Standardbred mares (n=18) with different reproductive status (eight healthy mares in first postpartum oestrus, five healthy barren mares and five mares with endometritis) were inseminated with frozen-thawed semen. Endometritis was evaluated during oestrus by bacteriological culture, cytology and presence of ultrasonically visible intrauterine fluid during oestrus. Concentrations of SAA, Hp and Fib were analysed in the blood in every 48h during oestrus and until 5, 6 or 7 days after AI. The day of sampling and number of blood samples varied between mares because of length of the oestrus and time of AI. Changes in concentrations of SAA, Hp and Fib were evaluated based on the day of sampling regard to AI and classification of the mares. There were no differences in SAA, Hp and Fib concentrations over time before or after AI or between the groups of mares. The insemination of mares with frozen-thawed semen did not increase the plasma concentrations of SAA, Hp and Fib above clinical threshold concentration and there were no differences between susceptible or healthy mares. PMID:24636940

  20. Acute phase proteins in salmonids: evolutionary analyses and acute phase response.

    PubMed

    Jensen, L E; Hiney, M P; Shields, D C; Uhlar, C M; Lindsay, A J; Whitehead, A S

    1997-01-01

    Inflammation induces dramatic changes in the biosynthetic profile of the liver, leading to increased serum concentrations of positive acute phase (AP) proteins and decreased concentrations of negative AP proteins. Serum amyloid A (SAA) and the pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) are major AP proteins: their serum levels can rise by 1000-fold, indicating that they play a critical role in defense and/or the restoration of homeostasis. We have cloned SAA and a SAP-like pentraxin from salmonid fish species. The salmonid SAA shares approximately 70% amino acid identity with mammalian AP SAA. When salmonids are challenged with an AP stimulus, i.e., Aeromonas salmonicida, SAA responds dramatically as a major AP reactant. The salmonid pentraxin shows approximately 40% amino acid identity to both mammalian SAP and CRP. Evolutionary analysis suggests the presence of only a single such protein in teleosts and lower animal species. Surprisingly, the salmonid pentraxin behaves as a negative AP reactant, reminiscent of the SAP-like Syrian hamster female protein, in that hepatic mRNA concentrations decline to 50% of prestimulus levels. This study reinforces the hypothesis that SAA induction is an essential and universal feature of the vertebrate AP response and that it represents part of an ancient host defense system. Conversely, the species-dependent heterogeneity of pentraxin expression during the vertebrate AP response supports the possibility that its most important ancestral (and perhaps present) function is not related to its AP behavior. PMID:8977214

  1. Acute phase protein response in Alpine ibex with sarcoptic mange.

    PubMed

    Rahman, Md Mizanur; Lecchi, Cristina; Fraquelli, Cristina; Sartorelli, Paola; Ceciliani, Fabrizio

    2010-03-25

    The acute phase proteins (APP) are a group of serum proteins that change their concentration in animals following external or internal challenges, such as infection, inflammation or stress. The concentrations of four APPs, including serum amyloid A (SAA), haptoglobin (Hp), alpha(1)-acid glycoprotein (AGP) and ceruloplasmin (Cp) were determined in serum collected from healthy Alpine ibexes (Capra ibex) and ibexes with Sarcoptes scabiei mange. Primary structures of all four APPs were determined by cDNA sequencing. The concentrations of all four APPs were higher in serum of animals with clinical signs of sarcoptic mange when compared to healthy animals. Two of the APPs, including SAA and AGP, acted as major APPs, since their serum concentrations were increased more than 10-folds when compared to healthy animals (P<0.001). The other two APPs, including Hp and Cp, acted as minor acute phase proteins, as their concentrations were increased from two to five folds (P<0.001). These findings provide a remarkable potential as diagnostic markers for the early detection of sarcoptic mange in free ranging animals. PMID:20036058

  2. Serum metabolomics study of the acute graft rejection in human renal transplantation based on liquid chromatography-mass spectrometry.

    PubMed

    Zhao, Xinjie; Chen, Jihong; Ye, Lei; Xu, Guowang

    2014-05-01

    Acute graft rejection is one of the most common and serious postcomplications in renal transplantation. A noninvasive method is needed to specifically monitor acute graft rejection. We investigated metabolic alterations of acute graft rejection in human renal transplantation by applying a metabolomics approach. Sera from 11 acute graft rejection subjects and 16 nonacute graft rejection subjects were analyzed by a nontargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach including both hydrophilic interaction chromatography and reversed-phase liquid chromatography separations. Discriminative metabolites of acute graft rejection after transplantation were detected, including creatinine, kynurenine, uric acid, polyunsaturated fatty acid, phosphatidylcholines, sphingomyelins, lysophosphatidylcholines, etc. The lower level of serum dehydroepiandrosterone sulfate was found in the acute graft rejection group before transplantation. The results revealed comprehensive metabolic abnormalities in acute graft rejection. The findings are valuable for the clinic noninvasive diagnosis or therapy of acute graft rejection. PMID:24641727

  3. Low serum levels of interleukin-6 in children with post-infective acute thrombocytopenic purpura.

    PubMed

    Gangarossa, S; Romano, V; Munda, S E; Sciotto, A; Schilirò, G

    1995-08-01

    Interleukin-6 plays an important role in host defense mechanisms and it appears to be a major mediator of the acute-phase response. IL-6 is also an important thrombocytopoietic factor. High serum levels of IL-6 are present in reactive thrombocytosis. The number and function of circulating platelets are the major factors that affect megakaryocytopoiesis by thrombopoietin. High levels of thrombopoietin have been observed in patients with thrombocytopenic purpura. To evaluate a possible thrombopoietin-like function of IL-6, we measured IL-6 levels in the serum of patients affected by post-infective acute thrombocytopenic purpura using a sensitive ELISSA assay. As controls, we studied normal subjects and patients with reactive thrombocytosis. No significant difference was observed between thrombocytopenic patients and normal controls. High IL-6 levels were present in patients with reactive thrombocytosis. In conclusion, we had not observed high levels of IL-6 in acute thrombocytopenic purpura and, very probably, IL-6 is not involved in the regulation of platelet mass for the hemostatic function. The thrombocytopoietic activity of IL-6 is another acute-phase response and it is consistent with the other functions of this cytokine. This suggests an active participation of platelets in host defense mechanisms. PMID:7628586

  4. Complement levels in acute infectious hepatitis and serum hepatitis

    PubMed Central

    Kosmidis, J. C.; Leader-Williams, Lesley K.

    1972-01-01

    The level of the third component of complement was measured in serial specimens of serum taken from thirty-one patients with acute viral hepatitis. Fourteen of the thirty-one patients were positive for the hepatitis-associated antigen. A characteristic fluctuation was observed in twenty-nine of the thirty-one patients. This consisted of an initial fall of the level of C3, followed by an increase to a higher than normal level and then a gradual return to normal. No difference was observed between the patients who were positive and those who were negative for the hepatitis-associated antigen. These results support the view that immune complexes play a significant role in the pathogenesis of acute viral hepatitis. PMID:4624985

  5. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection

    PubMed Central

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  6. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection.

    PubMed

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  7. Increased Interleukin-17 and decreased BAFF serum levels in drug-free acute schizophrenia.

    PubMed

    El Kissi, Yousri; Samoud, Samar; Mtiraoui, Ahlem; Letaief, Leila; Hannachi, Neila; Ayachi, Mouna; Ali, Bechir Ben Hadj; Boukadida, Jalel

    2015-01-30

    Hypotheses regarding an immune-cytokine basis of schizophrenia have been postulated with controversial findings and a lack of data related to many cytokines. The aim of this study was to assess serum levels of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Transforming Growth Factor-β (TGF-β), Interleukin-17 (IL-17) and B-cell Activating Factor (BAFF) in schizophrenic patients and to determine correlations between cytokine levels and clinical parameters. Serum cytokine levels were measured with ELISA techniques in 60 neuroleptic-free patients on acute phase of the disease (BPRS≥40) and 28 healthy controls matched for age and sex. Current symptoms were assessed with Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). No significant difference was found between patients and controls regarding IFN-γ serum levels. IL-4 was not detected in both groups. Patients exhibited significantly higher IL-17 and lower BAFF serum levels. IL-17 and BAFF levels were negatively correlated in schizophrenic patients. SANS global score was negatively correlated with IL-17 and positively correlated with IFN-γ serum levels. These results argue against the involvement of Th1 or Th2 population cells in schizophrenia. IL-17 and BAFF could be valuable markers for schizophrenia. PMID:25453636

  8. Pathobiochemical mechanisms during the acute phase response.

    PubMed

    Kleesiek, K; Greiling, H

    1984-01-01

    The acute phase response is characterised by the following sequence of principle phenomena: (1) an early local inflammatory reaction, (2) formation of inflammatory humoral factors inducing a systemic reaction, (3) stimulation of glycoprotein synthesis predominantly in the hepatocytes, and (4) an increase in the plasma concentration of acute phase proteins, when the rate of biosynthesis exceeds the degradation rate. Inflammatory mediators (lysosomal enzymes, oxygen derived radicals, prostaglandins) are mainly released during phagocytosis by granulocytes and macrophages. The signal reaching the hepatocytes is not yet clearly identified. A leukocyte endogenous mediator (LEM) released by macrophages is described. There is evidence that prostaglandins and probably proteinase alpha 2-macroglobulin complexes are also involved. The hepatic acute phase protein synthesis is modulated by hormones (insulin, cortisol, somatotropin). The biochemical events in the hepatocyte include an increase in protein synthesis and the regulatory control of the glycosylation of polypeptide precursors. The secreted glycoproteins serve variously as inhibitors or mediators of the inflammatory processes. PMID:6208159

  9. Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin.

    PubMed

    Karnezi, Dimitra; Ceron, Jose J; Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Martinez, Silvia; Tvarijonaviciute, Asta; Harrus, Shimon; Koutinas, Christos K; Pardali, Dimitra; Mylonakis, Mathios E

    2016-02-29

    There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post-inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting. PMID:26854345

  10. [Sequential changes in acute phase reactant proteins and complement activation in patients with acute head injuries].

    PubMed

    Ikeda, Y; Matsuura, H; Nakazawa, S

    1987-12-01

    The role of immunological mechanisms in head injury is not clearly defined. In this study we investigated the immunological function in patients with acute head injuries. Serum acute phase reactant proteins (APRP), complement activation and immunoglobulines as immunological parameters were studied. APRP are produced in the liver and increase in cancer patients as well as those with acute and chronic inflammations, trauma and autoimmune diseases. APRP are known to be one of the immunosuppressive factors in the serum. Forty patients with acute head injuries were studied. Thirty-four patients were male and six patients were female, ages ranged from 12 to 81 years. Serial blood samples were obtained during the first seven days of trauma. The Glasgow Coma Score (GCS) were recorded at the time of admission for all patients. Clinical outcome was assessed at the time of discharge according to the Glasgow Outcome Scale. The "good" group consisted of patients with good recovery or moderate disability. The "bad" group consisted of patients with severe disability, persistent vegetative state and death. The concentrations of immunoglobulines (IgG, IgM, IgA) were within normal range and humoral immunity was not affected. Complement activation at the time of admission was closely related to GCS (p less than 0.01), but the levels of C4, C3, and C3 activator except for these of CH50 were within normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2451531

  11. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    PubMed Central

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette; Poulsen, Karin T.; Campbell, Fiona M.; Eckersall, P. David; Heegaard, Peter M.H.

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14–18 h after lung infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14–18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase protein response occurring concomitantly with the hepatic response. This suggests that the acute phase protein response is a more disseminated systemic response than previously thought. The current study provides to our knowledge the first example of porcine extrahepatic expression and regulation of C-reactive protein, haptoglobin, fibrinogen, pig major acute phase protein, and transferrin in peripheral lymphoid tissues. PMID:19236838

  12. Analysis of Serum Th1/Th2 Cytokine Levels in Patients with Acute Mumps Infection

    PubMed Central

    Malaiyan, Jeevan; Ramanan, Padmasani Venkat; Subramaniam, Dinesh; Menon, Thangam

    2016-01-01

    Background: The mumps virus is frequently the causative agent of parotitis. There has been no study on serum cytokine levels of acute mumps parotitis except for a few which document cytokine levels in cerebrospinal fluid of mumps meningitis. It is with this notion, our study aimed to find Th1/Th2 cytokine levels from patients with acute mumps parotitis. Materials and Methods: Concentrations of mumps-specific IgM, mumps, measles, rubella-specific IgG antibody, and Th1/Th2 cytokines, namely interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 were measured simultaneously in serum from 74 patients (42 pediatric and 32 adult cases), 40 healthy subjects (20 pediatric and 20 adults) and in the supernatant of peripheral blood mononuclear cells stimulated with mumps virus genotype C which served as the positive control. Statistical significance was analyzed between each group by means of Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's rank correlation coefficient test. Results: IgM positivity confirmed acute infection in all 74 patients and of these 67 were vaccinated cases; however, very few of them (10/67) were positive for mumps IgG. We found that IFN-γ, IL-2, and IL-10 showed a statistically significant increase in both pediatric and adult patients with acute mumps infection when compared to healthy controls and values were comparable to the positive control. Conclusion: The Th1 cells play important roles during the acute phase of mumps parotitis. PMID:27293364

  13. Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

    PubMed Central

    McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

    2011-01-01

    Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global

  14. Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury.

    PubMed

    Wagner, Amy K; McCullough, Emily H; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L; Dobos, Julie A; Brett, Christopher A; Santarsieri, Martina; Dixon, C Edward; Berga, Sarah L; Fabio, Anthony

    2011-06-01

    Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for

  15. Maternal serum soluble CD30 is increased in pregnancies complicated with acute Pyelonephritis

    PubMed Central

    Kusanovic, Juan Pedro; Romero, Roberto; Espinoza, Jimmy; Gotsch, Francesca; Edwin, Samuel; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Soto, Eleazar; Erez, Offer; Mazaki-Tovi, Shali; Than, Nandor Gabor; Friel, Lara; Yoon, Bo Hyun; Mazor, Moshe; Hassan, Sonia

    2007-01-01

    Objectives Normal pregnancy is characterized by activation of the innate immunity and suppression of the adaptive limb of the immune response. However, pregnant women are more susceptible to the effects of infection and microbial products than non-pregnant women. CD30 is a member of the tumor necrosis factor receptor superfamily and is preferentially expressed by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) is proposed to be an index of Th2 immune response. High serum concentrations of sCD30 have been found in the acute phase of viral infections, such as HIV-1 and hepatitis B. There is, however, conflicting evidence about serum sCD30 concentration in patients with bacterial infections. The objective of this study was to determine whether there are changes in the serum concentration of sCD30 in pregnant women with pyelonephritis. Methods This cross-sectional study included normal pregnant women (N=89) and pregnant women with pyelonephritis (N=41). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests were used for comparisons. A p value <0.05 was considered statistically significant. Results (1) Pregnant women with pyelonephritis had a significantly higher median serum concentration of sCD30 than those with a normal pregnancy (median: 44.3 U/ml, range: 16–352.5 vs. median: 29.7 U/ml, range: 12.2–313.2, respectively; p<0.001); and (2) No significant differences were found in the median maternal serum concentration of sCD30 between pregnant women with pyelonephritis who had a positive blood culture compared to those with a negative blood culture (median:47.7 U/mL, range: 17.1–118.8 vs. median: 42.6 U/mL, range: 16–352.5, respectively; p=0.86). Conclusions Acute pyelonephritis during pregnancy is associated with a higher maternal serum concentration of sCD30 than normal pregnancy. This finding is novel, and suggests that pregnant women with pyelonephritis may

  16. Assessment of serum prolactin levels in acute myocardial infarction: The role of pharmacotherapy

    PubMed Central

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.; Awad, Mohamed S.; Alrifai, Sinan B.

    2016-01-01

    Background: Hyperprolactinemia may reflect neuroendocrine stress reaction against acute coronary syndromes. Aim: The aim of the present study was evaluation of the serum prolactin level in the acute myocardial infarction (MI) regarding the current pharmacotherapy in management of MI. Setting and Design: Cross-sectional clinical based study. Subjects and Methods: This cross-sectional clinical study involved all patients with acute MI in a coronary care unit, a total number of 44 patients (45% males and 55% females) with age ranged from 40 to 75 years. A full history for modifiable risk factors and current therapy with aspirin, clopidogrel and or metformin, all patients are nonsmokers. The anthropometric measurements; for estimations of body mass index (kg/m2), electrocardiography was obtained. Fasting blood samples were taken in the morning from all patients and the sera used for estimations of routine investigation and determination of ischemic cardiac biomarkers like cardiac troponin I (cTnI) and serum prolactin level. Results: This study shows a significant increase in the serum prolactin in acute MI as compared with the control. In acute MI serum cTnI elevation was correlated with serum prolactin increments. In metformin-treated group, there was a lowest prolactin serum level. Conclusions: Serum prolactin level increased in acute MI, and positively correlated with cardiac troponin level and reflects underlying cardiovascular complications. PMID:26904472

  17. The acute phase response in panic disorder.

    PubMed

    Herrán, Andrés; Sierra-Biddle, Deirdre; García-Unzueta, Maria Teresa; Puente, Jesús; Vázquez-Barquero, José Luis; Antonio Amado, José

    2005-12-01

    An acute-phase response (APR), manifested as an increase of acute-phase proteins has been shown in major depression. Panic disorder (PD) may share some aetiopathogenic mechanisms with depression, but APR has not been studied in this disorder. Forty-one panic patients in the first stages of their illness were compared with 32 healthy subjects of comparable sex, age, and body mass index. Clinical diagnosis was established with the mini international neuropsychiatric interview, and severity with the panic disorder severity scale and the CGI scale. Laboratory determinations included four acute phase proteins (APPs) [albumin, gammaglobulins, fibrinogen, C-reactive-protein (CRP)] and basal cortisol level. Patients were studied after 8-wk follow-up taking selective serotonin reuptake inhibitors (SSRIs) to assess the evolution of the APPs. Gammaglobulin levels were lower, and both cortisol and CRP levels were higher in PD patients than in controls. APP did not differ between patients with or without agoraphobia. At follow-up, patients who responded to SSRIs presented a decrease in albumin levels, and a trend towards a decrease in cortisol and CRP compared with levels at intake. The conclusions of this study are that there is an APR in patients suffering from PD, and this APR tends to diminish after a successful treatment with SSRIs. PMID:15927091

  18. MODULATION OF PHAGOCYTE FUNCTION BY OVOTRANSFERRIN, A CHICKEN ACUTE PHASE PROTEIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovotransferrin (OTF) is an acute phase protein in chickens the serum levels of which is elevated in response to inflammation and infections. To understand whether OTF may influence inflammation through its immunomodulatory effects, we studied its in vitro effects on chicken macrophage-like HD11 cell...

  19. Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages.

    PubMed

    Wong, Wing-Yan; Lee, Magnolia Muk-Lan; Chan, Brandon Dow; Kam, Richard Kin-Tin; Zhang, Ge; Lu, Ai-Ping; Tai, William Chi-Shing

    2016-04-01

    Macrophages are essential for the maintenance of intestinal homeostasis, and their activation has been proposed to be critical to the pathogenesis of inflammatory bowel disease (IBD). Although there are many recognized mediators of macrophage activation, increasing evidence suggests that macrophages respond to exosome stimulation. Exosomes are 40-150 nm microvesicles released from different cell types and are found in a variety of physiological fluids, including serum. As studies have shown that circulating exosomes participate in intercellular communication and can mediate the immune response, we hypothesized that exosomes may play a role in the pathogenesis of IBD though modulation of macrophage activity. In this study, we used the dextran sulfate sodium (DSS) induced acute colitis mice model to investigate the effect of serum exosomes on macrophages and identify exosome proteins potentially involved in macrophage activation. We treated RAW264.7 macrophages with serum exosomes isolated from dextran sulfate sodium induced mice and found that treatment induced phosphorylation of p38 and ERK and production of tumor necrosis factor α when compared to treatment with exosomes isolated from control mice. Subsequent proteomic analysis identified 56 differentially expressed proteins, a majority of which were acute-phase proteins and immunoglobulins. Bioinformatics analysis suggested these proteins were mainly involved in the complement and coagulation cascade, which has been implicated in macrophage activation. Our findings provide new insight into the role of circulating serum exosomes in acute colitis and contribute to the understanding of macrophage activation in the pathogenesis of IBD. PMID:26806198

  20. Acute phase proteins in cattle after exposure to complex stress.

    PubMed

    Lomborg, S R; Nielsen, L R; Heegaard, P M H; Jacobsen, S

    2008-10-01

    Stressors such as weaning, mixing and transportation have been shown to lead to increased blood concentrations of acute phase proteins (APP), including serum amyloid A (SAA) and haptoglobin, in calves. This study was therefore undertaken to assess whether SAA and haptoglobin levels in blood mirror stress in adult cattle. Six clinically healthy Holstein cows and two Holstein heifers were transported for four to six hours to a research facility, where each animal was housed in solitary tie stalls. Blood samples for evaluation of leukocyte counts and serum SAA and haptoglobin concentrations were obtained before (0-sample) and at 8, 24 and 48 hours after the start of transportation. Upon arrival the animals gave the impression of being anxious, and they appeared to have difficulty coping with isolation and with being tied on the slippery floors of the research stable. Serum concentrations of SAA and haptoglobin increased significantly in response to the stressors (P < 0.01 and 0.05 at 48 hours, respectively). Additionally, the animals had transient neutrophilia at 8 and 24 hours (P < 0.05). In conclusion, the results of the study suggest that SAA and haptoglobin may serve as markers of stress in adult cattle. PMID:18461465

  1. Oral iron acutely elevates bacterial growth in human serum

    PubMed Central

    Cross, James H.; Bradbury, Richard S.; Fulford, Anthony J.; Jallow, Amadou T.; Wegmüller, Rita; Prentice, Andrew M.; Cerami, Carla

    2015-01-01

    Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses. PMID:26593732

  2. No alteration in serum leptin levels during acute endotoxemia in sheep.

    PubMed

    Soliman, M; Abdelhady, S; Fattouh, I; Ishioka, K; Kitamura, H; Kimura, K; Saito, M

    2001-10-01

    To determine the role of leptin in endotoxin-induced anorexia in ruminants, circulating leptin levels were measured during acute experimental endotoxemia in sheep. Injection of bacterial lipopolysaccharide (450 ng/kg, i.v.) induced anorexia accompanied with fever and increases in serum levels of cortisol, insulin and glucose which are known to stimulate leptin secretion in rodent and human, while it did not affect serum leptin levels at all. These results indicate that serum leptin levels in sheep during acute endotoxemia are differentially regulated from those in rodent and human, and that leptin might not be involved in the endotoxin-induced anorexia in sheep. PMID:11714034

  3. Acute- phase response and iron status markers among pulmonary tuberculosis patients: a cross-sectional study in Mwanza, Tanzania.

    PubMed

    Friis, Henrik; Range, Nyagosya; Braendgaard Kristensen, Camilla; Kaestel, Pernille; Changalucha, John; Malenganisho, Wabyahe; Krarup, Henrik; Magnussen, Pascal; Bengaard Andersen, Ase

    2009-07-01

    Fe status is difficult to assess in the presence of infections. To assess the role of the acute- phase response (APR) and other predictors of serum ferritin and transferrin receptor, we conducted a cross-sectional study among pulmonary tuberculosis (PTB) patients in Mwanza, Tanzania. The acute- (serum ferritin) phase protein, serum alpha1-antichymotrypsin (ACT) and serum ferritin and serum soluble transferrin receptor (sTfR) were measured, and data on smoking, soil and alcohol intake, and infection status were collected. Linear regression analysis was used to assess the role of elevated serum ACT and other predictors of serum ferritin and serum sTfR. Of 655 patients, 81.2 % were sputum positive (PTB+) and 47.2 % HIV+. Mean serum ACT was 0.72 g/l, with 91.1 % above 0.4 g/l. Among females and males, respectively, geometric mean serum ferritin was 140.9 and 269.1 microg/l (P < 0.001), and mean serum sTfR 4.3 and 3.8 mg/l (P < 0.001). Serum sTfR was increased 0.5 mg/l and log serum ferritin increased linearly with serum ACT >0.4 g/l. PTB+ and HIV infection, alcohol drinking and smoking were the positive predictors of serum ferritin, and female sex, soil eating, Schistosoma mansoni and hookworm infection were the negative predictors. Similarly, smoking and HIV infection were the negative predictors of serum sTfR, and female sex, soil eating and PTB+ were the positive predictors. Serum ferritin and serum sTfR are affected by the APR, but may still provide information about Fe status. It may be possible to develop algorithms, based on the markers of the APR and Fe status, to assess the Fe status among the patients with tuberculosis or other infections eliciting an APR. PMID:19175946

  4. Procalcitonin beyond the acute phase: novel biomediator properties?

    PubMed

    Panico, Carolina; Nylen, Eric

    2013-01-01

    Since inflammation has been linked to carcinogenic events, discovery of relevant biomarkers may have important preventative implications. Procalcitonin (ProCT) has been shown to be an important prognostic biomarker in severe inflammatory conditions, but there is no data regarding its biomarker role, if any, beyond the acute phase. In a recent study published in BMC Medicine, Cotoi et al. analyzed whether serum ProCT levels in healthy individuals are associated with mortality outcomes. The results are affirmative in that baseline ProCT was shown to be strongly and independently associated with all-cause and cancer mortality and with the incidence of colon cancer in men. By contrast, the study indicated that high sensitivity C-reactive protein was independently associated with cardiovascular mortality but not with cancer mortality in men. Thus, baseline levels of ProCT appear to have prognostic biomarker implications potentially related to its emerging biomediator action(s). PMID:23984981

  5. Acute phase glycoproteins: bystanders or participants in carcinogenesis?

    PubMed

    Dempsey, Eugene; Rudd, Pauline M

    2012-04-01

    Acute phase proteins (APPs) are a group of serum proteins that undergo dramatic changes in concentration during times of inflammation. Many APPs are heavily glycosylated, and their sugar content and complexity change in the presence of cancer-induced chronic inflammation. These changes in glycosylation are currently being exploited in the search for novel biomarkers of cancer. Like other posttranslational modifications, such as phosphorylation, changes in glycosylation can profoundly alter the function of a protein. We hypothesize that besides being a rich source of potential biomarkers APPs may also play an active role in tumorigenesis. The glycan content of the APPs haptoglobin and kininogen, for example, is altered in many types of cancer. These APPs can interact with a number of receptors on macrophages in the tumor microenvironment, potentially modulating macrophage activity and thereby contributing to tumor cell survival, growth, and metastasis. PMID:22352780

  6. Serum estrogen levels in men with acute myocardial infarction.

    PubMed

    Klaiber, E L; Broverman, D M; Haffajee, C I; Hochman, J S; Sacks, G M; Dalen, J E

    1982-12-01

    Serum estradiol and serum estrone levels were assessed in 29 men in 14 men in whom myocardial infarction was ruled out; in 12 men without apparent coronary heart disease but hospitalized in an intensive care unit; and in 28 men who were not hospitalized and who acted as control subjects. (The 12 men who were hospitalized but who did not have coronary heart disease were included to control for physical and emotional stress of a severe medical illness.) Ages ranged from 21 to 56 years. Age, height, and weight did not differ significantly among groups. Blood samples were obtained in the patient groups on each of the first three days of hospitalization. The serum estrone level was significantly elevated in all four patient groups when compared with that in the control group. Estrone level, then, did not differentiate patients with and without coronary heart disease. Serum estradiol levels were significantly elevated in the groups with myocardial infarction, unstable angina, and in the group in whom myocardial infarction was ruled out. However, estradiol levels were not significantly elevated in the group in the intensive care unit without coronary heart disease when compared to the level in the normal control group. Serum estradiol levels, then, were elevated in men with confirmed or suspected coronary heart disease but were not elevated in men without coronary heart disease even under the stressful conditions found in an intensive care unit. Serum estradiol levels were significantly and positively correlated (p less than 0.03) with serum total creatine phosphokinase levels in the patients with myocardial infarction. The five patients with myocardial infarction who died within 10 days of admission had markedly elevated serum estradiol levels. The potential significance of these serum estradiol elevations is discussed in terms of estradiol's ability to enhance adrenergic neural activity and the resultant increase in myocardial oxygen demand. PMID:7148879

  7. Acute Phase Proteins and Their Role in Periodontitis: A Review.

    PubMed

    Polepalle, Tejaswin; Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-11-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  8. Acute Phase Proteins and Their Role in Periodontitis: A Review

    PubMed Central

    Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-01-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  9. C-reactive protein and the acute phase reaction in geriatric patients.

    PubMed

    Bertsch, Thomas; Triebel, Jakob; Bollheimer, Cornelius; Christ, Michael; Sieber, Cornel; Fassbender, Klaus; Heppner, Hans Jürgen

    2015-10-01

    The C-reactive protein (CRP), first described as a serum component capable of precipitating the C-polysaccharide of pneumococci, is one of the most important proteins because the serum concentration rises in the acute phase reaction. The acute phase reaction is the nonspecific reaction of the body to noxious stimuli of the most varied kinds, such as infections, burns, neoplasms and tissue trauma. The CRP is synthesized in liver parenchymal cells by cytokines which are derived from stimulated leucocytes and released into the circulation. Because of its molecular structure and in synergy with the complement system, it is able to precipitate and/or lyse microorganisms, thereby rendering them harmless. Measurement of the serum CRP concentration can provide important information with respect to the diagnosis and monitoring of treatment. Due to immunosenescence in geriatric patients the synthesis of CRP appears to be limited to inflammatory stimuli; however, this phenomenon does not appear to be of major clinical relevance. Despite the introduction of new parameters of the acute phase reaction, sometimes with better performance, such as interleukin-6, procalcitonin and the soluble endotoxin receptor sCD14, measurement of CRP for diagnosis and treatment monitoring is still justified even in geriatric patients as testing is rapid, economic and nearly ubiquitously available round the clock. Biochemical markers of the acute phase reaction should always be interpreted together with the clinical picture and their specific limitations. PMID:26334841

  10. Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia

    PubMed Central

    DiNardo, Courtney D.; Propert, Kathleen J.; Loren, Alison W.; Paietta, Elisabeth; Sun, Zhuoxin; Levine, Ross L.; Straley, Kimberly S.; Yen, Katharine; Patel, Jay P.; Agresta, Samuel; Abdel-Wahab, Omar; Perl, Alexander E.; Litzow, Mark R.; Rowe, Jacob M.; Lazarus, Hillard M.; Fernandez, Hugo F.; Margolis, David J.; Tallman, Martin S.; Luger, Selina M.

    2013-01-01

    Cancer-associated isocitrate dehydrogenase (IDH) mutations produce the metabolite 2-hydroxyglutarate (2HG), but the clinical utility of 2HG has not been established. We studied whether 2HG measurements in acute myeloid leukemia (AML) patients correlate with IDH mutations, and whether diagnostic or remission 2HG measurements predict survival. Sera from 223 de novo AML patients were analyzed for 2HG concentration by reverse-phase liquid chromatography–mass spectrometry. Pretreatment 2HG levels ranged from 10 to 30 000 ng/mL and were elevated in IDH-mutants (median, 3004 ng/mL), compared to wild-type IDH (median, 61 ng/mL) (P < .0005). 2HG levels did not differ among IDH1 or IDH2 allelic variants. In receiver operating characteristic analysis, a discriminatory level of 700 ng/mL optimally segregated patients with and without IDH mutations, and on subsequent mutational analysis of the 13 IDH wild-type samples with 2HG levels >700 ng/mL, 9 were identified to have IDH mutations. IDH-mutant patients with 2HG levels >200 at complete remission had shorter overall survival compared to 2HG ≤200 ng/mL (hazard ratio, 3.9; P = .02). We establish a firm association between IDH mutations and serum 2HG concentration in AML, and confirm that serum oncometabolite measurements provide useful diagnostic and prognostic information that can improve patient selection for IDH-targeted therapies. PMID:23641016

  11. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  12. BCL11A expression in acute phase chronic myeloid leukemia.

    PubMed

    Yin, Jiawei; Zhang, Fan; Tao, Huiquan; Ma, Xiao; Su, Guangsong; Xie, Xiaoli; Xu, Zhongjuan; Zheng, Yanwen; Liu, Hong; He, Chao; Mao, Zhengwei Jenny; Wang, Zhiwei; Chang, Weirong; Gale, Robert Peter; Wu, Depei; Yin, Bin

    2016-08-01

    Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons. PMID:27285855

  13. Acute phase proteins response to feed deprivation in broiler chickens.

    PubMed

    Najafi, P; Zulkifli, I; Soleimani, A F; Goh, Y M

    2016-04-01

    Feed deprivation in poultry farming imposes some degree of stress to the birds, and adversely affects their well -being. Serum levels of acute phase proteins (APP) are potential physiological indicators of stress attributed to feed deprivation. However, it has not been determined how long it takes for a measurable APP response to stressors to occur in avian species. An experiment was designed to delineate the APP and circulating levels of corticosterone responses in commercial broiler chickens to feed deprivation for 30 h. It was hypothesized that feed deprivation would elicit both APP and corticosterone (CORT) reactions within 30 h that is probably associated with stress of hunger. Twenty-one day old birds were subjected to one of 5 feed deprivation periods: 0 (ad libitum, AL), 6, 12, 18, 24, and 30 h. Upon completion of the deprivation period, blood samples were collected to determine serum CORT, ovotransferrin (OVT), α1-acid glycoprotein (AGP), and ceruloplasmin (CP) concentrations. Results showed that feed deprivation for 24 h or more caused a marked elevation in CORT (P=0.002 and P<0.0001, respectively) when compared to AL. However, increases in AGP (P=0.0005), CP (P=0.0002), and OVT (P=0.0003) were only noted following 30 h of feed deprivation. It is concluded that elicitation of AGP, CP, and OVT response may represent a more chronic stressful condition than CORT response in assessing the well-being of broiler chickens. PMID:26908886

  14. Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

    PubMed Central

    O’Malley, Stephanie S.; Gueorguieva, Ralitza; Wu, Ran; Jatlow, Peter I.

    2015-01-01

    Background Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods 18 healthy individuals (8 cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL, in random order in 3 laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45 am prior to drinking, at 2 pm, and at 7:45 the next morning. Mixed effects regression models compared baseline and 24 hr. post-drinking bilirubin concentrations. Results Total serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24 hours in non-smokers (from Mean=0.38, SD=0.24 to Mean=0.51 SD=0.30, F(1, 32.2) =24.24, p<.0001) but not in smokers (from Mean=0.25, SD=0.12 to Mean=0.26, SD=0.15, F(1, 31.1) =0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. Conclusions Alcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies. PMID:25707709

  15. Serum activity of angiotensin converting enzyme 2 is decreased in patients with acute ischemic stroke.

    PubMed

    Bennion, Douglas M; Rosado, Christian A; Haltigan, Emily A; Regenhardt, Robert W; Sumners, Colin; Waters, Michael F

    2016-07-01

    Levels of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase, are dynamically altered after stroke in preclinical models. We sought to characterize the previously unexplored changes in serum ACE2 activity of stroke patients and the mechanism of these changes. Serum samples were obtained from patients during acute ischemic stroke (n=39), conditions mimicking stroke (stroke-alert, n=23), or from control participants (n=20). Enzyme activity levels were analyzed by fluorometric assay and correlated with clinical variables by regression analyses. Serum ACE2 activity was significantly lower in acute ischemic stroke as compared to both control and stroke-alert patients, followed by an increase to control levels at three days. Serum ACE2 activity significantly correlated with the presence of ischemic stroke after controlling for other factors (P=0.01). Additional associations with ACE2 activity included a positive correlation with systolic blood pressure at presentation in stroke-alert (R(2)=0.24, P=0.03), while stroke levels showed no correlation (R(2)=0.01, P=0.50). ACE2 sheddase activity was unchanged between groups. These dynamic changes in serum ACE2 activity in stroke, which concur with preclinical studies, are not likely to be driven primarily by acute changes in blood pressure or sheddase activity. These findings provide new insight for developing therapies targeting this protective system in ischemic stroke. PMID:27488276

  16. Assessment of serum and urine ghrelin levels in patients with acute stroke

    PubMed Central

    Seyhanli, Eyyup Sabri; Lok, Ugur; Gulacti, Umut; Buyukaslan, Hasan; Atescelik, Metin; Yildiz, Mustafa; Onur, Mehmet Ruhi; Goktekin, Mehmet Cagri; Aydın, Suleyman

    2015-01-01

    Introduction: Ghrelin is a novel brain-gut peptide hormone consisted of 28 amino-acid. In the plasma, it exists in two major molecular forms, acylated and des-acyled ghrelin, filtered in glomeruli or secreted by nephrons. Primary biological effects of hormones are regulating appetite, foods intake and energy metabolism. We investigated the changing and relationships between serum and urine ghrelin levels in acute stroke patients to provide more information whether diagnostic parameter. Methods: Thirty acute stroke patients and thirty consecutive volunteers included in study prospectively. To analyze serum and urine ghrelin levels, at the time of diagnose, all of participant blood and fresh urine (1 ml serum, 2 ml urine respectively) samples were obtained. Serum ghrelin levels analyzed ELISA technique, and urine ghrelin levels studied by validation technique. To compare quantitative data student’s t test, and for qualitative data chi-square and Fisher’s Exact Chi-square test was used. P<0.05 was considered statistically significant. Results: Urine acyl ghrelin levels found statistically significant between patient and control groups (P=0.001), but there were no statistically significant differences between both groups (P>0.05) in serum acyl gherelin, des-acyl ghrelin and urine des-acyle ghrelin levels. Conclusions: The results indicate that urine acyl ghrelin levels may be considered as a diagnostic parameter in acute ischemic stroke patients. Further studies delineating the mechanism of these observed results are warranted. PMID:25785049

  17. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis

    PubMed Central

    Elmoslemany, Ahmed M.

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  18. The diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis.

    PubMed

    El-Deeb, Wael M; Elmoslemany, Ahmed M

    2016-01-01

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep. PMID:27547520

  19. ACUTE PHASE PROTEINS AS A MARKER OF RESPIRATORY INFLAMMATION IN PRZEWALSKI'S HORSE (EQUUS FERUS PRZEWALSKII).

    PubMed

    Sander, Samantha J; Joyner, Priscilla H; Cray, Carolyn; Rotstein, David S; Aitken-Palmer, Copper

    2016-06-01

    Acute phase proteins are sensitive markers of inflammation, which are highly conserved across taxa. Although the utility of these proteins are becoming well defined in human and domestic animal medical fields, their role in nondomestic species remains unclear. In this communication, a 20-yr-old Przewalski's horse was presented for unresolving aspiration pneumonia, which cultured a unique Actinomyces-like bacteria. Despite waxing and waning clinical signs and minimal changes on baseline hematologic analysis, protein electrophoresis, serum amyloid A, and surfactant protein D serum concentrations showed changes that more accurately reflected the clinical severity of this case. PMID:27468045

  20. Serum annexin A2 levels in acute brucellosis and brucellar spondylodiscitis.

    PubMed

    Aktug Demir, N; Kolgelier, S; Sumer, S; Inkaya, A C; Ozcimen, S; Demir, L S; Ural, O; Arpaci, A

    2014-10-01

    Brucellosis is a chronic granulomatous infection and may present with various clinical manifestations. Brucellar spondylodiscitis symptoms are initially subtle and nonspecific. Annexin A2 (ANXA2) is involved in various biological functions, including osteoclast formation, bone resorption, and cell growth regulation. In this study, we aimed to determine the clinical significance of serum ANXA2 levels in acute brucellosis and brucellar spondylodiscitis. This prospective study included 96 acute brucellosis patients and 51 healthy controls. Acute brucellosis was diagnosed by a 1/160 or higher titer in a standard tube agglutination (STA) test or a four-fold increase in titers between two STA tests performed two weeks apart in the presence of clinical symptoms within the last eight weeks and/or growth of Brucella spp. in appropriately prepared culture media. ANXA2 levels were determined with an enzyme-linked immunosorbent assay (ELISA). Forty (41.7 %) of 96 acute brucellosis patients were male and 56 (58.3 %) were female. Serum ANXA2 levels were elevated in patients compared to healthy controls (p = 0.001). Eighteen of 96 (18.7 %) acute brucellosis patients had brucellar spondylodiscitis. The serum ANXA2 levels of patients with brucellar spondylodiscitis were higher than those of patients with acute disease without brucellar spondylodiscitis (p = 0.001). ANXA2, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values were elevated in the brucellar spondylodiscitis group compared to patients without brucellar spondylodiscitis. Serum ANXA2 measurement together with ESR and CRP is thought to be indicative in the diagnosis of brucellar spondylodiscitis, a common complication of brucellosis. PMID:24853056

  1. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria

    PubMed Central

    Agarwal, Banwari; Davenport, Andrew

    2014-01-01

    Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease (MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period. PMID:25349641

  2. Acute ischemic non-embolic stroke and serum level of uric acid

    PubMed Central

    Sheykholeslami, Nazanin Zia; Gadari, Faranak; Ahmady, Jafar

    2012-01-01

    Background Impact of high level of uric acid on stroke is still controversial. We conducted this study to investigate the relationship between acute ischemic non-embolic stroke and serum levels of uric acid. Methods This was a case-control study on patients with acute ischemic non-embolic stroke in Rafsanjan, Iran. The control group consisted of normal persons who were similar to the case group in terms of age and gender. Serum level of uric acid in the first 24 hours of admission was measured with photometry method. Results In a total of 130 patients (59 mens), hyperuricemia was seen in 13.0% of subjects in the control group and 10.7% of subjects in the case group. Nine patients in case group and 7 patients in control group with hyperuricemia were women. No significant relationship was found between acute ischemic non-embolic stroke and serum level of uric acid. Conclusion There was no relationship between uric acid and acute ischemic non-embolic stroke. PMID:24250850

  3. Activity of phosphoglycerate mutase and its isoenzymes in serum after acute myocardial infarction

    PubMed Central

    Durany, N; Carballo, E; Joseph, J; Bedini, J L; Bartrons, R; Ballesta, A M; Carreras, J

    1996-01-01

    Aims/background—In humans there are three phosphoglycerate mutase (PGM, EC 5.4.12.1) isoenzymes (MM, MB and BB) which have similar distribution and developmental pathways to creatine kinase (CK, EC 2.7.3.2) isoenzymes. Total serum PGM activity increases in acute myocardial infarction with the same time course as creatine kinase activity. The present study was undertaken to determine changes in the activity of PGM and its isoenzymes after acute myocardial infarction. Methods—PGM activity was measured spectrophotometrically, by coupling the formation of 2-phosphoglycerate from 3-phosphoglycerate with enolase, pyruvate kinase and lactate dehydrogenase catalysed reactions. Inter- and intra-assay reproducibility was assessed. PGM isoenzyme activities were measured using cellulose acetate electrophoresis. Results—Total PGM activity in serum was increased in patients with a confirmed diagnosis of acute myocardial infarction. PGM activity peaked 12 to 24 hours after the onset of symptoms and returned to normal values within 48 hours. Electrophoretic analysis of serum from healthy subjects showed a band corresponding to BB-PGM and two other artefactual bands that did not correspond to adenylate kinase. After myocardial infarction, BB-PGM activity increased and MB-PGM and MM-PGM could be detected. On immunoblot analysis, normal serum contained an inactive form of MM-PGM with a smaller molecular weight than that of PGM tissue isoenzymes. Conclusions—Total serum PGM activity increased in patients with acute myocardial infarction, following the same temporal course as creatine kinase activity. The increase in MM-PGM and MB-PGM activities in these patients was not as high as expected. It is suggested that PGM isoenzymes, after release into the blood, undergo postsynthetic, probably proteolytic, transformation. Images PMID:16696092

  4. Effects of Prepubertal Acute Immobilization Stress on Serum Kisspeptin Level and Testis Histology in Rats.

    PubMed

    Maalhagh, Mehrnoosh; Jahromi, Abdolreza Sotoodeh; Yusefi, Alireza; Razeghi, Ali; Zabetiyan, Hassan; Karami, Mohammad Yasin; Madani, Abdol Hossein

    2016-01-01

    Stress has inhibitory effect on HPG axis through increasing cortisol serum level. In this study, the effect of acute prepubertal stress on kisspeptin, which plays essential role in puberty achievement is assessed. To do this experimental study thirty immature healthy male wistar rats of 4 weeks old and without any symptoms of puberty were selected randomly. These rats were divided into three groups, randomly. Two groups were chosen as control and pretest and one as stress (test) group. Immobilization stress was applied for 10 days and serum level of cortisol, testosterone and kisspeptin were measured. Primary and secondary spermatocyte and sertoli cell evaluated and compared among groups. Mean serum level of kisspeptin in pretest group, control group and stress (test) group were 0.0381 ± 0.0079, 91.0500 ± 4.87430 and 15.2156 ± 3.88135 pg mL(-1) respectively. Serum level of kisspeptin had significant differences between three groups (p < 0.001). Acute prepubertal immobilization stress led to decrease in serum level of kisspeptin and testosterone in stress (test) group compared to control groups. Also stress caused a significant decrease in the numbers of secondary spermatocytes of the test group. PMID:26930799

  5. Serum and salivary cardiac analytes in acute myocardial infarction related to oral health status

    NASA Astrophysics Data System (ADS)

    Ebersole, Jeffrey L.; Kryscio, Richard J.; Campbell, Charles; Kinane, Denis F.; McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Miller, Craig S.

    2014-06-01

    With the advent of an increased emphasis on the potential to utilize biomarkers in saliva for systemic diseases, the issue of existing oral disease is an important consideration that could adversely affect the interpretation of diagnostic results obtained from saliva. We addressed the question does a patient's oral inflammation status confound biomarker levels used in diagnosis of acute myocardial infarction (AMI). The results demonstrated that multiple serum biomarkers and a few salivary biomarkers reflected the cardiac event. Importantly, oral health of the individual had minimal impact on the validity of the serum or salivary biomarker effectiveness.

  6. Serum Triglyceride Level: A Predictor of Complications and Outcomes in Acute Pancreatitis?

    PubMed Central

    Tariq, Hassan; Gaduputi, Vinaya; Peralta, Richard; Abbas, Naeem; Nayudu, Suresh Kumar; Thet, Phyo; Zaw, Tin; Hui, Shirley; Chilimuri, Sridhar

    2016-01-01

    Aim. To study serum triglyceride level as a predictor of complications and outcomes in acute pancreatitis. Methods. In this retrospective observational study, 582 patients admitted with acute pancreatitis, who had serum triglyceride levels measured within the first 24 hours, were divided into two groups. The study group consisted of patients with a triglyceride level ≥2.26 mmol/L (group 2) and the control group consisted of triglyceride level of <2.26 mmol/L (group 1). We collected data for baseline demographics, laboratory values, incidence of complications (local and systemic), admission to the intensive care unit (ICU), ICU length of stay, length of total hospital stay, and death in the two groups. Results. A triglyceride level of ≥2.26 mmol/L was found to be an independent predictor of developing altered mental status (p: 0.004), pancreatic necrosis (p: 0.001), acute respiratory distress syndrome (p: 0001), systemic Inflammatory response syndrome (p: 0.001), acute kidney injury (p: 0.001), hospital length of stay (LOS) (p: 0.002), admission to intensive care unit (ICU) (p: 0.002), and ICU LOS (p: 0.003). Conclusion. A triglyceride level of ≥2.26 mmol/L on admission in acute pancreatitis is an independent predictor of developing local and systemic complications, hospital LOS, admission to ICU, and ICU LOS.

  7. Serum from patients with hepatitis E virus-related acute liver failure induces human liver cell apoptosis

    PubMed Central

    WU, FAN; WANG, MINXIN; TIAN, DEYING

    2014-01-01

    The pathogenesis of acute liver failure has not been fully elucidated. The present study investigated the effects of the serum from patients with hepatitis E virus (HEV)-related acute liver failure on human liver cell survival and apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS) antibody recognizing core polysaccharide against acute liver failure serum-induced apoptosis. Serum was collected from patients with HEV-related acute liver failure. The levels of endotoxin (LPS) in the serum were measured using a quantitative tachypleus amebocyte lysate endotoxin detection kit with a chromogenic endpoint. Serum with a mean concentration of LPS was incubated with L02 human liver cells and the rate of apoptosis was detected by flow cytometry. The apoptotic rate was also evaluated in liver cells incubated with antibody and the HEV-related acute liver failure serum. The results indicated that the concentration of LPS in the serum of patients with HEV-related acute liver failure was 0.26±0.02 EU/ml, which was significantly higher than that of the control group (P<0.05). The rate of apoptosis in the human liver cells induced by acute liver failure serum was 5.83±0.42%, which was significantly increased compared with that in the cells treated with the serum of healthy individuals (P<0.05). The apoptotic rate of the cells incubated with antibody and the acute liver failure serum was 5.53±0.51%, which was lower than that of the cells incubated with acute liver failure serum alone (P>0.05). These results indicate that the serum of patients with HEV-related acute liver failure induces the apoptosis of human liver cells. LPS may be directly involved in the apoptosis of human liver cells. Moreover, the presence of the antibody did not significantly reduce the level of apoptosis of liver cells exposed to HEV-related acute liver failure serum. PMID:24348810

  8. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  9. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

    PubMed

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-03-01

    Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective

  10. Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction.

    PubMed

    Ahmad, Ghayyor; Sial, Gull Zareen Khan; Ramadori, Pierluigi; Dudas, Jozsef; Batusic, Danko S; Ramadori, Giuliano

    2011-12-01

    Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression. PMID:21963450

  11. Serum neurogranin measurement as a biomarker of acute traumatic brain injury

    PubMed Central

    Yang, Jun; Korley, Frederick K.; Dai, Min; Everett, Allen D.

    2015-01-01

    Objectives Neurogranin (NRGN) is a small neuronal protein that plays an important role in synaptic signaling by regulating calmodulin (CaM) availability. In this study, we developed an ELISA to measure NRGN quantitatively in serum samples from a cohort of acute traumatic brain injury (TBI) patients and a non-TBI control cohort, and explored the potential value of NRGN as a circulating biomarker for TBI. Design and methods Recombinant His-NRGN protein was used to develop mouse monoclonal capture and rabbit polyclonal detection antibodies, and they were used to develop a sandwich ELISA. After validation, we used this ELISA to measure serum samples from a cohort of typical adult acute TBI patients (N = 76 TBI cases) and non-TBI control patients (N = 150 controls). Results The NRGN ELISA lower limit of detection was 0.055 ng/mL, lower limit of quantification was 0.2 ng/mL, and interassay CVs were ≤ 10.7%. The average recovery was 99.9% (range from 97.2–102%). Serum NRGN concentrations in TBI cases were significantly higher than in controls (median values were 0.18 ng/mL vs. 0.02 ng/mL, p < 0.0001), but did not discriminate TBI cases with intracranial hemorrhage (p = 0.09). Conclusions We have developed a highly sensitive and reproducible ELISA for measuring circulating NRGN in blood samples. Serum NRGN concentrations in acute TBI patients were significantly higher than in controls, indicating that NRGN could have utility as a circulating biomarker for acute TBI. This report provides evidence to support larger and controlled TBI clinical studies for NRGN validation and prediction of outcomes. PMID:26025774

  12. Activity of "nonspecific pancreatic carboxylesterase" in rat serum in experimentally induced acute pancreatitis (preliminary results).

    PubMed

    Kálmán, A; Kálmán, Z; Velösy, G; Vargha, G; Vargha, G; Papp, M

    1989-01-01

    The aim of this study was to obtain more information on the serum level of "nonspecific pancreatic carboxylesterase" (PCE) in experimentally induced acute pancreatitis in rats. The effects of caerulein stimulation, hepatic duct ligation, bile-pancreatic duct ligation or the effect of retrograde injection of saline, 5% taurocholate and sunflower oil were investigated. The activity of PCE and amylase was measured in the serum, pancreatic tissue, pancreatic juice and ascitic fluid. The changes in PCE activity were greater (both in directions to increase or decrease) than that of amylase, produced by different experimental procedures. The results confirm the thesis that the serum activity of PCE is a more sensitive diagnostic method than that of amylase to detect the inflammatory process in the pancreas or the effect of obstruction of the pancreatic duct. PMID:2480696

  13. Serum complements and heart fatty acid binding protein in Bangladeshi patients with acute myocardial infarction

    PubMed Central

    Akhtar, Nayareen; Taher, Abu; Rahman, Rezwanur; Chowdhury, Ashesh Kumar

    2012-01-01

    The complement system is activated following acute myocardial infarction (AMI). Heart fatty acid binding protein (H-FABP) is a sensitive early biomarker of myocardial necrosis that can be used to confirm or exclude a diagnosis of AMI and to monitor recurrent infarction. This study was designed to detect changes in C3, C4 and H-FABP after AMI. Forty patients with AMI and a control group of 40 apparently healthy people were included. Selections were based on inclusion and exclusion criteria. The baseline characteristics were not significantly different between the groups. Patients’ blood samples were collected within 12 h of admission. Significant increases in C3 (AMI group 1.4260+0.04, healthy group 1.26040+0.04; p<0.05), C4 (AMI group 0.29305±0.013, healthy group 0.20860±0.012; p<0.05) and H-FABP (AMI group 12.3±1.69, healthy group 0.16±0.057; p<0.001) were seen in patients with AMI. The correlation between serum C3 and body mass index (BMI, r=0.33; p<0.05), serum C4 and BMI(r=0.313; p<0.05), serum C3 and total cholesterol high density lipoprotein (HDL, r=0.32; p<0.05), serum C4 and HbA1C (r=0.335; p<0.05) and serum C3 and troponin I (r= 0.325p<0.05) was found to be significant. But the correlation between serum C3 and waist:hip ratio (p=0.56), serum C4 and waist:hip ratio (p=0.83), serum C4 and total cholesterol HDL (p=0.993), serum C3 and HbA1C (p=0.440), serum C3 and random blood sugar (p=0.563), serum C4 and random blood sugar (p=0.828) and serum C4 and troponin I (p=0.373) was not significant. The significant complement activation detected in the plasma of patients with AMI indicated that complement plays a part in the pathogenesis of myocardial infarction. A significant increase of H-FABP improves the diagnosis of AMI.

  14. Hypovitaminosis D is common among pulmonary tuberculosis patients in Tanzania but is not explained by the acute phase response.

    PubMed

    Friis, Henrik; Range, Nyagosya; Pedersen, Marianne L; Mølgaard, Christian; Changalucha, John; Krarup, Henrik; Magnussen, Pascal; Søborg, Christian; Andersen, Ase B

    2008-12-01

    Vitamin D is essential to immune function, but little is known about the vitamin D status in equatorial populations. A cross-sectional study was conducted among pulmonary tuberculosis (PTB) patients in Mwanza, Tanzania to identify the predictors of their vitamin D status. Data on sociodemography, season, and intake of food, alcohol, tobacco, and soil were collected, anthropometric measurements taken, and serum alpha(1)-antichymotrypsin (ACT), ferritin and soluble transferrin receptor (sTfR), and serum 25-hydroxy-(ergocalciferol+cholecalciferol) [25(OH)D] determined. Of the 655 patients studied, 79.7% (508/637) were culture-positive (PTB+) and 47.2% HIV infected. Mean serum ACT, an acute phase reactant, was 0.73 +/- 0.25 g/L with 69.2% >0.6 g/L. Mean serum 25(OH)D was 86.6 +/- 32.9 nmol/L, with 41.2% <75 nmol/L. Serum 25(OH)D was highest during the harvest season, May to July, compared with the remaining year. Single subjects had lower [10.4 (95% CI 4.0; 16.9) nmol/L] serum 25(OH)D concentrations than married subjects and PTB+ patients had concentrations lower [8.2 (95% CI 1.5; 14.9) nmol/L] than PTB- patients. Serum 25(OH)D increased with consumption of a large freshwater fish but not of small dried fish or other foods. BMI and serum TfR were positive predictors of serum 25(OH)D, whereas neither elevated serum ACT nor HIV were predictors. In conclusion, serum 25(OH)D is a valid measure of vitamin D status during the acute phase response. The lower concentrations in PTB+ patients may reflect lower sun exposure or increased utilization. The health consequences of hypovitaminosis D in low-income equatorial populations, at risk for both infectious and chronic diseases, should be studied. PMID:19022975

  15. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

    PubMed

    Lorente, Leonardo; Martín, María M; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541-18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  16. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

    PubMed Central

    Lorente, Leonardo; Martín, María M.; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  17. A reversed-phase high performance liquid chromatography method for quantification of methotrexate in cancer patients serum.

    PubMed

    Li, Yuan-dong; Li, Yan; Liang, Ning-sheng; Yang, Fan; Kuang, Zhi-peng

    2015-10-01

    A simple, rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method has been developed for the determination of methotrexate in human serum. After deproteinization of the serum with 40% silver nitrate solution, methotrexate and internal standard (IS) were separated on a reversed-phase column with a mobile phase consisting of 10mM sodium phosphate buffer (pH6.40)-methanol (78:22%, v/v) and ultraviolet detection at 310nm. The linearity is evaluated by a calibration curve in the concentration range of 0.05-10.0μg/mL and presented a correlation coefficient of 0.9995. The absolute recoveries were 97.52±3.9% and 96.87±3.7% for methotrexate and ferulic acid (internal standard), respectively. The intra- and inter-day precision were less 6.19 and 5.89%, respectively (n=6). The limit of quantitation was 0.02μg/mL and the limit of detection was 0.006μg/mL. The complete analysis was achieved less than 10min with no interference from endogenous components or 22 examined drugs. This method was validated by using serum samples from high-dose methotrexate treated patients with osteosarcoma, breast cancer, acute leukemia and lymphoma. The method was demonstrated to be a simple, rapid and reliable approach in quantification of methotrexate in serum samples from patients with high-dose methotrexate therapy. PMID:26319303

  18. Butyrylcholinesterase as a marker of inflammation and liver injury in the acute and subclinical phases of canine ehrlichiosis.

    PubMed

    do Carmo, Guilherme M; Crivellenti, Leandro Z; Bottari, Nathieli B; Machado, Gustavo; Borin-Crivellenti, Sofia; Moresco, Rafael N; Duarte, Thiago; Duarte, Marta; Tinucci-Costa, Mirela; Morsch, Vera M; Schetinger, Maria Rosa C; Stefani, Lenita M; Da Silva, Aleksandro S

    2015-12-01

    The aim of this study was to evaluate the role of butyrylcholinesterase (BChE) as a marker of inflammation and liver injury in the acute and subclinical phases of canine ehrlichiosis. Forty-two serum samples of dogs naturally infected with Ehrlichia canis were used, of which 24 were from animals with the acute phase of the disease and 18 with subclinical disease. In addition, sera from 17 healthy dogs were used as negative controls. The hematocrit, BChE activity, hepatic injury (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), nitric oxide, and cytokines levels were evaluated. The BChE activity was significantly elevated (P<0.05) in dogs with the acute phase of the disease when compared to healthy animals. However, there was a reduction on BChE activity on dogs with subclinical disease compared to the other two groups. AST and ALT levels were significantly higher (P<0.05) in the acute phase, as well as the inflammatory mediators (NOx, TNF-α, INF-γ, IL-4, IL-6) when compared to the control group. On the other hand, IL-10 levels were lower in the acute phase. Based on these results, we are able to conclude that the acute infection caused by E. canis in dogs leads to an increase on seric BChE activity and some inflammatory mediators. Therefore, this enzyme might be used as a marker of acute inflammatory response in dogs naturally infected by this bacterium. PMID:26616656

  19. Acute lithium administration selectively lowers tyrosine levels in serum and brain

    PubMed Central

    McFarlane, Hewlet G.; Steele, John; Vinion, Keenan; Bongiovanni, Rodolfo; Double, Manda; Jaskiw, George E.

    2016-01-01

    Lithium exerts anti-dopaminergic behavioral effects. We examined whether some of these might be mediated by changes in brain levels of tyrosine (TYR), the precursor to dopamine. Lithium chloride (LiCl2) 3.0 mEq/kg IP acutely lowered serum TYR and the ratio of serum TYR to other large neutral amino acids (LNAAs); it also selectively lowered striatum TYR levels as measured in tissue or in vivo. While LiCl2 3.0 mEq/kg IP also augmented haloperidol (0.19 mg/kg SC)-induced catalepsy, this lithium effect was not attenuated by administration of TYR 100 mg/kg IP. We conclude that lithium acutely and selectively lowers brain TYR by lowering serum levels of tyrosine relative to the LNAAs that compete with it for transport across the blood–brain barrier. However, the lowering of TYR does not appear to significantly contribute to the ability of lithium to potentiate haloperidol-mediated catalepsy. PMID:21962398

  20. Early post parturient changes in milk acute phase proteins.

    PubMed

    Thomas, Funmilola C; Waterston, Mary; Hastie, Peter; Haining, Hayley; Eckersall, P David

    2016-08-01

    The periparturient period is one of the most critical periods in the productive life of a dairy cow, and is the period when dairy cows are most susceptible to developing new intramammary infections (IMI) leading to mastitis. Acute phase proteins (APP) such as haptoglobin (Hp), mammary associated serum amyloid A3 (M-SAA3) and C-reactive protein (CRP) have been detected in milk during mastitis but their presence in colostrum and milk in the immediate postpartum period has had limited investigation. The hypothesis was tested that APP are a constituent of colostrum and milk during this period. Enzyme linked immunosorbent assays (ELISAs) were used to determine each APP's concentration in colostrum and milk collected daily from the first to tenth day following calving in 22 Holstein-Friesian dairy cows. Haptoglobin was assessed in individual quarters and composite milk samples while M-SAA3 and CRP concentration were determined in composite milk samples. Change in Hp in relation to the high abundance proteins during the transition from colostrum to milk were evaluated by 1 and 2 dimension electrophoresis and western blot. In 80% of the cows all APPs were detected in colostrum on the first day following parturition at moderately high levels but gradually decreased to minimal values in the milk by the 6th day after calving. The remaining cows (20%) showed different patterns in the daily milk APP concentrations and when an elevated level is detected could reflect the presence of IMI. Demonstration that APP are present in colostrum and milk following parturition but fall to low levels within 4 days means that elevated APP after this time could be biomarkers of post parturient mastitis allowing early intervention to reduce disease on dairy farms. PMID:27600971

  1. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    SciTech Connect

    Shannahan, Jonathan H.; Alzate, Oscar; Winnik, Witold M.; Andrews, Debora; Schladweiler, Mette C.; Ghio, Andrew J.; Gavett, Stephen H.; Kodavanti, Urmila P.

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  2. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A.; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-01-01

    Abstract Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a

  3. Age- and Sex-Associated Effects on Acute-Phase Proteins in Göttingen Minipigs

    PubMed Central

    Christoffersen, Berit Ø; Jensen, Søren J; Ludvigsen, Trine P; Nilsson, Sara K; Grossi, Anette B; Heegaard, Peter M H

    2015-01-01

    Göttingen minipigs are a useful model for diseases having an inflammatory component, and the associated use of acute-phase proteins (APP) as biomarkers of inflammation warrants establishment of their reference ranges. The objective of this study was to establish reference values for selected APP in Göttingen minipigs and to investigate the effects of age, sex, and various stimuli on these ranges. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, pig major acute-phase protein (PMAP), albumin, and porcine α-1 acid glycoprotein (PAGP) were evaluated in 4 age groups (6, 16, 24 and 40–48 wk) of male and female Göttingen minipigs. In addition, minipigs were tested under 2 housing conditions, after acute LPS challenge, and after diet-induced obesity with and without mild diabetes. Changing the pigs to a new environment induced significant increases in CRP, PMAP, haptoglobin and PAGP and a decrease in albumin. An acute LPS stimulus increased CRP, PMAP, haptoglobin, and SAA; PAGP was unchanged and albumin decreased. Obese pigs with and without diabetes showed increases in CRP and PAGP, albumin decreased, and haptoglobin and SAA were unchanged. PMAP was increased only in obese pigs without diabetes. In conclusion, reference values for CRP, PMAP, haptoglobin, SAA, PAGP and albumin were established for male and female Göttingen minipigs of different ages. These APP were influenced by age and sex, underlining the importance of considering these factors when designing and interpreting studies including aspects of inflammation. In addition, an APP response was verified after both acute and chronic stimuli. PMID:26310463

  4. Initial Serum Ammonia as a Predictor of Neurologic Complications in Patients with Acute Glufosinate Poisoning

    PubMed Central

    Lee, Dong Keon; Youk, Hyun; Kim, Hyun; Kim, Oh Hyun; Go, Jin; Kim, Tae Hoon; Cha, KyoungChul; Lee, Kang Hyun; Hwang, Sung Oh

    2016-01-01

    Purpose Glufosinate poisoning can cause neurologic complications that may be difficult to treat due to delayed manifestation. Studies assessing possible predictors of complications are lacking. Although serum ammonia level is a potential predictor of severe neurotoxicity, it has only been assessed via case reports. Therefore, we investigated factors that predict neurologic complications in acute glufosinate-poisoned patients. Materials and Methods We conducted a retrospective review of 45 consecutive glufosinate-poisoning cases that were diagnosed in the emergency department (ED) of Wonju Severance Christian Hospital between May 2007 and July 2014. Patients with a Glasgow Coma Scale (GCS) score of <8, seizure, and/or amnesia were defined to a neurologic complication group. Results The neurologic complication group (29 patients, 64.4%) comprised patients with GCS<8 (27 patients, 60.0%), seizure (23 patients, 51.1%), and amnesia (5 patients, 11.1%). Non-neurologic complications included respiratory failure (14 patients, 31.1%), intubation and ventilator care (23 patients, 51.1%), shock (2 patients, 4.4%), pneumonia (16 patients, 35.6%), acute kidney injury (10 patients, 22.2%), and death (4 patients, 8.9%). Complications of GCS<8, seizure, respiratory failure, and intubation and ventilator care appeared during latent periods within 11 hrs, 34 hrs, 14 hrs, and 48 hrs, respectively. Initial serum ammonia was a predictor of neurologic complications [odds ratio 1.039, 95% confidence interval (1.001-1.078), p=0.046 and area under the curve 0.742]. Conclusion Neurologic complications developed in 64.4% of patients with acute glufosinate poisoning. The most common complication was GCS<8. Initial serum ammonia level, which can be readily assessed in the ED, was a predictor of neurologic complications. PMID:26632409

  5. Pig α1-Acid Glycoprotein: Characterization and First Description in Any Species as a Negative Acute Phase Protein

    PubMed Central

    Heegaard, Peter M. H.; Miller, Ingrid; Sorensen, Nanna Skall; Soerensen, Karen Elisabeth; Skovgaard, Kerstin

    2013-01-01

    The serum protein α1-acid glycoprotein (AGP), also known as orosomucoid, is generally described as an archetypical positive acute phase protein. Here, porcine AGP was identified, purified and characterized from pooled pig serum. It was found to circulate as a single chain glycoprotein having an apparent molecular weight of 43 kDa by SDS-PAGE under reducing conditions, of which approximately 17 kDa were accounted for by N-bound oligosaccharides. Those data correspond well with the properties of the protein predicted from the single porcine AGP gene (ORM1, Q29014 (UniProt)), containing 5 putative glycosylation sites. A monoclonal antibody (MAb) was produced and shown to quantitatively and specifically react with all microheterogenous forms of pig AGP as analyzed by 2-D electrophoresis. This MAb was used to develop an immunoassay (ELISA) for quantification of AGP in pig serum samples. The adult serum concentrations of pig AGP were in the range of 1–3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2–5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase protein. PMID:23844161

  6. Serum myeloperoxidase: a novel biomarker for evaluation of patients with acute coronary syndrome

    PubMed Central

    Gururajan, P; Gurumurthy, P; Nayar, P; Babu, S; Sarasabharati, A; Victor, D; Cherian, K M

    2009-01-01

    Objectives Myeloperoxidase, an abundant leucocyte enzyme, is elevated in culprit lesions that have ruptured in patients with sudden cardiac injury. Multiple lines of evidence suggest an association between myeloperoxidase and inflammation and acute coronary syndrome. Myeloperoxidase has been proposed as a potent risk marker and diagnostic tool in acute coronary syndrome (ACS). Recent studies have reported the potential use of myeloperoxidase in acute coronary syndrome, but limited reports are available on its utility in different groups of ACS in the emergency department. Therefore the circulating levels of serum myeloperoxidase in patients with acute coronary syndrome and control subjects were studied. Design and setting The levels of serum myeloperoxidase were measured by ELISA in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as non-cardiac chest pain (NCCP). The levels of myeloperoxidase were significantly increased in patients with ACS when compared with controls and NCCP. From the receiver operator characteristic (ROC) curve analysis, the optimum value above which myeloperoxidase can be considered positive was found to be 48.02 U/ml. The area under the curve was found to be 0.956 with 95% CI (0.934 to 0.973) (p<0.0001). A combination analysis of ROC curves of troponin, creatine kinase MB (CK-MB) and myeloperoxidase showed myeloperoxidase to be highly significant. Multivariate analysis revealed myeloperoxidase to be an independent diagnostic marker for early diagnosis of ACS. Conclusion Myeloperoxidase, in contrast to troponin and CK-MB, identified patients at risk of ischaemic events, even in the absence of myocardial necrosis, thus highlighting its potent usefulness for risk stratification among patients presenting with chest pain.

  7. Serum visfatin concentration in acutely ill and weight-recovered patients with anorexia nervosa.

    PubMed

    Seidel, Maria; King, Joseph A; Ritschel, Franziska; Döpmann, Johanna; Bühren, Katharina; Seitz, Jochen; Roessner, Veit; Westphal, Sabine; Egberts, Karin; Burghardt, Roland; Wewetzer, Christoph; Fleischhaker, Christian; Hebebrand, Johannes; Herpertz-Dahlmann, Beate; Ehrlich, Stefan

    2015-03-01

    Visfatin is a recently described protein that is thought to regulate the process of adipocyte differentiation. Findings suggest that visfatin may be actively involved in the control of weight regulatory networks. However, to what extent and which role it plays in eating disorders is still poorly understood, as mixed results have been reported. The aim of the current study was to investigate serum visfatin concentrations on a cross sectional sample between acute anorexia nervosa patients (n=44), weight recovered patients (n=13) and healthy controls (n=46) and a longitudinal sample of acute patients (n=57) during weight recovery at three different time-points. Results did not show significant differences in visfatin between the three groups; however, acute patients showed a higher visfatin/BMI-SDS ratio than controls and recovered patients. Longitudinal results revealed an increase of visfatin levels during therapy. Our results suggest that high ratios of visfatin/BMI-SDS could be a state marker in acute anorexia nervosa, displaying a compensatory mechanism of the individual to maintain normal visfatin levels under malnourished conditions. PMID:25617618

  8. [Diagnostic importance of pentraxins at the early phase of acute pancreatitis].

    PubMed

    Meryk, Piotr; Dumnicka, Paulina; Kuśnierz-Cabala, Beata; Kuźniewski, Marek; Kapusta, Maria; Gurda-Duda, Anna; Goebels, Marek; Pawlica-Gosiewska, Dorota; Kulig, Jan

    2014-01-01

    Pentraxins are among the main acute phase reactants. There are two types of pentraxins, i.e., long, including pentraxin 3 (PTX3) and short, including C-reactive protein (CRP) and serum amyloid A (SAA). The aim of the study was to assess the increase in serum concentrations of pentraxins (ex- pressed as the multiplicity of the upper reference limits) and their usefulness in prognosing severe course of acute pancreatitis (AP) in the early phase of the disease. Forty patients admitted to Ist Department of Surgery, Jagiel-Ionian University Medical College with the diagnosis of AP were recruited for the study. In the early phase of AP, the concentrations of PTX3 achieved maximum earlier than CRP or SAA, enabling to differentiate between mild and moderate or severe AP in the first day of the disease. Also, during the first 24 hours from beginning of AP, SAA achieved its best prognostic value. Of all pentraxins studied, SAA was characterized by the most significant increase as compared to the upper reference limit. The prognostic utility of CRP increased later, after 48 hours of AP. PMID:25344970

  9. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. [The nutrition of acute phase in patients with metabolic syndrome].

    PubMed

    Tsutsumi, Rie; Sebe, Mayu

    2016-03-01

    In this session, we describe the acute phase in patients with metabolic syndrome from two sides; acute disease that occurs higher in patients with metabolic syndrome such as colonary heart disease and stroke, and acute aggravation of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome. The electrolyte imbalance is frequently detected in critical ill patients. It is reported that the extreme abnormalities of ionized calcium concentrations are independent predictors of mortality. In addition, from clinical database MIMIC-Ⅱ,calcium supplementation improves clinical outcome in intensive care unit patients. Although metabolic syndrome; lifestyle-related disease, is a chronic disease, the possibility of falling into acute disease by having it becomes very high and improvement of electrolyte imbalance, especially hypocalcaemia is expected to effective on clinical outcome. PMID:26923986

  11. The serum protein fetuin-B is involved in the development of acute myocardial infarction.

    PubMed

    Jung, Seung Hyo; Won, Kyung-Jong; Lee, Kang Pa; Kim, Hyun-Joong; Seo, Eun-Hye; Lee, Hwan Myung; Park, Eun Seok; Lee, Seung Hyun; Kim, Bokyung

    2015-07-01

    The rupture of an atherosclerotic plaque is one of the main causes of coronary artery thrombotic occlusion, leading to myocardial infarction. However, the exact mechanism and causal risk factors for plaque rupture remain unclear. To identify a potential molecule that can influence atherosclerotic plaque rupture, we investigated protein expression in serum from patients with acute myocardial infarction (AMI) and stable angina (SA), using proteomic analysis. The expression of six proteins, including fibrinogen, fetuin-B, keratin 9, proapolipoprotein and fibrinogen, were altered in serum from patients with AMI compared with serum from those with SA. Of these, fetuin-B, proapolipoprotein, fibrinogen γ-B-chain precursors and fibrinogen expression were greater in serum from patients with AMI than from patients with SA. Increased fetuin-B expression in serum from AMI patients was also confirmed by Western blot analysis. Treatment with recombinant human fetuin-B increased the migration in monocytes and macrophages in a concentration-dependent manner. Fetuin-B also affected vascular plaque-stabilizing factors, including lipid deposition and cytokine production in macrophages, the activation of matrix metalloproteinase (MMP)-2 in monocytes, and the activation of apoptosis and MMP-2 in vascular smooth muscle cells. Moreover, in vivo administration of fetuin-B decreased the collagen accumulation and smooth muscle cell content and showed an increased number of macrophages in the vascular plaque. From these results, we suggest that fetuin-B may act as a modulator in the development of AMI. This study may provide a therapeutic advantage for patients at high risk of AMI. PMID:25671698

  12. Serum Procalcitonin as a Useful Serologic Marker for Differential Diagnosis between Acute Gouty Attack and Bacterial Infection

    PubMed Central

    Song, Jung-Soo

    2016-01-01

    Purpose Patients with gout are similar to those with bacterial infection in terms of the nature of inflammation. Herein we compared the differences in procalcitonin (PCT) levels between these two inflammatory conditions and evaluated the ability of serum PCT to function as a clinical marker for differential diagnosis between acute gouty attack and bacterial infection. Materials and Methods Serum samples were obtained from 67 patients with acute gouty arthritis and 90 age-matched patients with bacterial infection. Serum PCT levels were measured with an enzyme-linked fluorescent assay. Results Serum PCT levels in patients with acute gouty arthritis were significantly lower than those in patients with bacterial infection (0.096±0.105 ng/mL vs. 4.94±13.763 ng/mL, p=0.001). However, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels showed no significant differences between the two groups. To assess the ability of PCT to discriminate between acute gouty arthritis and bacterial infection, the areas under the curves (AUCs) of serum PCT, uric acid, and CRP were 0.857 [95% confidence interval (CI), 0.798–0.917, p<0.001], 0.808 (95% CI, 0.738–0.878, p<0.001), and 0.638 (95% CI, 0.544–0.731, p=0.005), respectively. There were no significant differences in ESR and white blood cell counts between these two conditions. With a cut-off value of 0.095 ng/mL, the sums of sensitivity and specificity of PCT were the highest (81.0% and 80.6%, respectively). Conclusion Serum PCT levels were significantly lower in patients with acute gouty attack than in patients with bacterial infection. Thus, serum PCT can be used as a useful serologic marker to differentiate between acute gouty arthritis and bacterial infections. PMID:27401644

  13. Lower Serum Caveolin-1 Is Associated with Cerebral Microbleeds in Patients with Acute Ischemic Stroke

    PubMed Central

    Zhang, Jun; Zhu, Wusheng; Xiao, Lulu; Cao, Qinqin; Zhang, Hao; Wang, Huaiming; Ye, Zusen; Hao, Yonggang; Dai, Qiliang; Sun, Wen; Liu, Xinfeng; Ye, Ruidong

    2016-01-01

    Caveolin-1 (Cav-1) plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD) in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs), silent lacunar infarcts (SLIs), and white matter hyperintensities (WMHs). After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77–9.30). However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59–10.25) and with multiple CMBs (OR: 3.18, 95% CI: 1.16–8.72). These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD. PMID:27119011

  14. Nickel concentrations in serum of patients with acute myocardial infarction or unstable angina pectoris

    SciTech Connect

    Leach, C.N. Jr.; Linden, J.V.; Hopfer, S.M.; Crisostomo, M.C.; Sunderman, F.W. Jr.

    1985-01-01

    Nickel was measured, by electrothermal atomic absorption spectrophotometry, in sera from (a) 30 healthy adults, (b) 54 patients with acute myocardial infarction, (c) 33 patients with unstable angina pectoris without infarction, and (d) five patients with coronary atherosclerosis who developed cardiac ischemia during treadmill exercise. Mean (and SD) concentrations in Group a were 0.3 (0.3) ..mu..g/L (range <0.05-1.1 ..mu..g/L). Within 72 h after hospital admission, hypernickelemia (Ni greater than or equal to 1.2 ..mu..g/L) was found in 41 patients of group b (76%) and in 16 patients of group c (48%). Hypernickelemia was found before and after exercise in one patient of Group d (20%). Peak values averaged 3.0 ..mu..g/L (range 0.4-21 ..mu..g/L) in Group b, 1.5 ..mu..g/L (range <0.05-3.3 ..mu..g/L) in Group c. In Group b, the mean time interval between the peak values for creatine kinase activity and for nickel was 18 h. Serum nickel concentrations were unrelated to age, sex, time of day, cigarette smoking, medications, clinical complications, or outcome. Mechanisms and sources of release of nickel into the serum of patients with acute myocardial infarction or unstable angina pectoris are conjectural, but hypernickelemia may be related to the pathogenesis of ischemic myocardial injury. 25 references, 2 figures, 6 tables.

  15. STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

    PubMed Central

    Kunzevitzky, Noelia; Guttridge, Denis C.; Khuri, Sawsan; Koniaris, Leonidas G.; Zimmers, Teresa A.

    2011-01-01

    Background Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia. Methodology/Principal Findings Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. Conclusions/Significance These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such

  16. Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans

    PubMed Central

    Darton, Thomas C.; Blohmke, Christoph J.; Giannoulatou, Eleni; Waddington, Claire S.; Jones, Claire; Sturges, Pamela; Webster, Craig; Drakesmith, Hal; Pollard, Andrew J.; Armitage, Andrew E.

    2015-01-01

    Background Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/Principal Findings Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/Significance We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S

  17. Acute Phase Proteins in Response to Dictyocaulus viviparus Infection in Calves

    PubMed Central

    Gånheim, C; Höglund, J; Waller, K Persson

    2004-01-01

    Three experiments were carried out to examine the acute phase response, as measured by the acute phase proteins (APP) haptoglobin, serum amyloid A (SAA) and fibrinogen, in calves infected with lungworm, Dictyocaulus vivparus. In addition, eosinophil counts were analysed. Three different dose models were used in 3 separate experiments: I) 250 D. viviparus infective third stage larvae (L3) once daily for 2 consecutive days, II) 100 D. viviparus L3 once daily for 5 consecutive days, and III) 2000 L3 once. All 3 dose regimes induced elevated levels of haptoglobin, SAA and fibrinogen, although there was considerable variation both between and within experiments. A significant increase was observed in all 3 APP at one or several time points in experiment I and III, whereas in experiment II, the only significant elevation was observed for fibrinogen at one occasion. The eosinophil numbers were significantly elevated in all 3 experiments. The results show that lungworm infection can induce an acute phase response, which can be monitored by the selected APP. Elevated APP levels in combination with high numbers of eosinophils in an animal with respiratory disease may be used as an indicator of lung worm infection, and help the clinician to decide on treatment. However, high numbers of eosinophils and low levels of APP do not exclude a diagnosis of lungworm. Thus, lungworm infection may not be detected if measurements of APP are used to assess calf health in herds or individual animals. PMID:15535088

  18. Antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during early phase of acute otitis media.

    PubMed

    Karjalainen, H; Koskela, M; Luotonen, J; Herva, E; Sipilä, P

    1990-01-01

    Serum type (IgG, IgM and IgA-class) and secretory type antibodies specific to Streptococcus pneumoniae (Pn), Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 serum and 114 middle ear effusion (MEE) samples from 85 children with acute otitis media (AOM). The samples were obtained within 12 h from the onset of the ear symptoms. Serum (but not secretory) type antibodies to the infecting Pn serotype were found in 24% of the MEE samples of the patients with Pn AOM and, correspondingly, serum and/or secretory type antibodies to Hi and Br were seen in 54% and 63% of the MEE samples of the patients with Hi or Br AOM, respectively. Moreover, antibodies against bacteria other than the causative one could also be found in the MEE. The occurrence of the serum type antibodies against these bacteria in the MEE was closely correlated with their serum levels. The findings of this study indicate that during the very early phase of AOM, the MEE contains both serum type antibodies originating from the serum, and secretory antibodies of middle ear origin. Among them there are antibodies specific to the three most common bacteria causing AOM (Pn, Hi, and Br) regardless of the bacterial etiology of the AOM attack in question. PMID:2106760

  19. Emergence of the acute-phase protein hemopexin in jawed vertebrates

    PubMed Central

    Dooley, Helen; Buckingham, E. Bryan; Criscitiello, Michael F.; Flajnik, Martin F.

    2010-01-01

    When released from damaged erythrocytes free heme not only provides a source of iron for invading bacteria but is also highly toxic due to its ability to catalyze free radical formation. Hemopexin (Hx) binds free heme with very high affinity and thus protects against heme toxicity, sequesters heme from pathogens, and helps conserve valuable iron. Hx is also an acute-phase serum protein (APP), whose expression is induced by inflammation. To date Hx has been identified as far back in phylogeny as bony fish where it is called Warm-temperature Acclimation-related 65 kDa Protein (WAP65), as serum protein levels are increased at elevated environmental temperatures as well as by infection. During analysis of nurse shark (Ginglymostoma cirratum) plasma we isolated a Ni2+-binding serum glycoprotein and characterized it as the APP Hx. We subsequently cloned Hx from nurse shark and another cartilaginous fish species, the little skate Leucoraja erinacea. Functional analysis showed shark Hx, like that of mammals, binds heme but is found at unusually high levels in normal shark serum. As an Hx orthologue could not be found in the genomes of jawless vertebrates or lower deuterostomes it appears to have arisen just prior to the emergence of jawed vertebrates, coincident with the second round of genome wide duplication and the appearance of tetrameric haemoglobin (Hb). PMID:20884052

  20. Serum folate, cobalamin, homocysteine and methylmalonic acid concentrations in pigs with acute, chronic or subclinical Lawsonia intracellularis infection.

    PubMed

    Grützner, Niels; Gebhart, Connie J; Lawhorn, Bruce D; Suchodolski, Jan S; Steiner, Jörg M

    2015-03-01

    Lawsonia intracellularis is the causative agent of porcine proliferative enteropathy. The clinical presentation can be acute (i.e. proliferative hemorrhagic enteropathy, PHE), chronic (i.e. porcine intestinal adenomatosis, PIA) or subclinical. In humans with chronic enteropathies, low serum folate (vitamin B(9)) and cobalamin (vitamin B(12)) concentrations have been associated with increased serum concentrations of homocysteine and methylmalonic acid (MMA), which reflect the availability of both vitamins at the cellular level. The aim of this study was to evaluate serum folate, cobalamin, homocysteine and MMA concentrations in serum samples from pigs with PHE, PIA or subclinical L. intracellularis infection, and in negative controls. Serum folate, cobalamin, homocysteine and MMA concentrations differed significantly among pigs in the PHE, PIA, subclinical and negative control groups. Serum folate concentrations in the PHE and PIA groups were lower than in the subclinical and negative control groups, while serum cobalamin concentrations were lower in the PIA group than in other groups. Serum concentrations of homocysteine were higher in the PHE, PIA and subclinical groups than in the negative control group. Serum concentrations of MMA were higher in the subclinical and PIA groups than in the control group. These data suggest that pigs infected with L. intracellularis have altered serum cobalamin, folate, homocysteine and MMA concentrations. PMID:25618855

  1. Serum, Saliva, and Urine Irisin with and Without Acute Appendicitis and Abdominal Pain

    PubMed Central

    Bakal, Unal; Aydin, Suleyman; Sarac, Mehmet; Kuloglu, Tuncay; Kalayci, Mehmet; Artas, Gokhan; Yardim, Meltem; Kazez, Ahmet

    2016-01-01

    A 112-amino-acid protein irisin (IRI) is widely expressed in many organs, but we currently do not know whether appendix tissue and blood cells express it. If appendix tissue and neutrophil cells express IRI, measuring its concentration in biological fluids might be helpful in the diagnosis of acute appendicitis (AA), since neutrophil cells are the currently gold-standard laboratory parameters for the diagnosis of AA. Therefore, the purpose of this study was to investigate the suitability of enzyme-linked immunosorbent assay-based measurements of the proposed myokine IRI for the discrimination of patients with AA from those with acute abdominal pain (AP) and healthy controls. Moreover, immunoreactivity to IRI was investigated in appendix tissues and blood cells. Samples were collected on admission (T1), 24 hours (T2), and 72 hours (T3) postoperatively from patients with suspected AA and from patients with AP corresponding to T1–T3, whereas control subject blood was once corresponding to T1. IRI was measured in serum, saliva, and urine by using enzyme-linked immunosorbent assay, whereas in appendix tissue and blood cells, IRI was detected by immunohistohcemistry. Appendix tissue and blood cells (except for erythrocytes) are new sources of IRI. Basal saliva, urine, and serum levels were higher in children with AA compared with postoperative levels (T2) that start to decline after surgery. This is in line with the finding that IRI levels are higher in children with AA when compared with those with AP or control subject levels, most likely due to a large infiltration of neutrophil cells in AA that release its IRI into body fluids. Measurement of IRI in children with AA parallels the increase or decrease in the neutrophil count. This new finding shows that the measurement of IRI and neutrophil count can together improve the diagnosis of AA, and it can distinguish it from AP. IRI can be a candidate marker for the diagnosis of AA and offers an additional parameter to

  2. Time dependent alterations of serum matrix metalloproteinase-1 and metalloproteinase-1 tissue inhibitor after successful reperfusion of acute myocardial infarction.

    PubMed Central

    Hirohata, S.; Kusachi, S.; Murakami, M.; Murakami, T.; Sano, I.; Watanabe, T.; Komatsubara, I.; Kondo, J.; Tsuji, T.

    1997-01-01

    OBJECTIVE: To test the hypothesis that changes in serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) after acute myocardial infarction reflect extracellular matrix remodelling and the infarct healing process. PATIENTS: 13 consecutive patients with their first acute myocardial infarction who underwent successful reperfusion. METHODS: Blood was sampled on the day of admission, and on days 2, 3, 4, 5, 7, 14, and 28. Serum MMP-1 and TIMP-1 were measured by one step sandwich enzyme immunoassay. Left ventricular volume indices were determined by left ventriculography performed four weeks after the infarct. RESULTS: Serum concentrations of both MMP-1 and TIMP-1 changed over time. The average serum MMP-1 was more than 1 SD below the mean control values during the initial four days, increased thereafter, reaching a peak concentration around day 14, and then returned to the middle control range. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum MMP-1 on day 5, when it began to rise, and for the magnitude of rise in MMP-1 on day 5 compared to admission. Serum TIMP-1 at admission was more than 1 SD below the mean control value, and increased gradually thereafter, reaching a peak on around day 14. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum TIMP-1 on days 5 and 7, and for the magnitude of rise in TIMP-1 on days 5 and 7 compared to admission. CONCLUSIONS: Both MMP-1 and TIMP-1 showed significant time dependent alteration after acute myocardial infarction. Thus MMP-1 and TIMP-1 may provide useful information in evaluating the healing process as it affects left ventricular remodelling after acute myocardial infarction. PMID:9391291

  3. Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant

    SciTech Connect

    Liu Zhilin; Ukomadu, Chinweike

    2008-01-25

    Fibrinogen-like protein 1 (FGL1) is a hepatocyte derived protein that is upregulated in regenerating rodent livers following partial hepatectomy. It has been implicated as a mitogen for liver cell proliferation. In this study, we show that recombinant human IL-6 induces FGL1 expression in Hep G2 cells in a pattern similar to those of acute phase reactants. Following induction of acute inflammation in rats by subcutaneous injection of turpentine oil, serum FGL1 levels are also enhanced. Although, a recent report suggests that FGL1 associates almost exclusively with the fibrin matrix, we report here that approximately 20% of the total plasma FGL1 remains free. The enhancement of FGL1 levels in vitro by IL-6 and its induction after turpentine oil injection suggest that it is an acute phase reactant. Its presence in bound and free forms in the blood also implies biological roles that extend beyond the proposed autocrine effect it has on hepatocytes during regeneration.

  4. Serum Adiponectin and Cardiometabolic Risk in Patients with Acute Coronary Syndromes

    PubMed Central

    Oliveira, Gustavo Bernardes de Figueiredo; França, João Ítalo Dias; Piegas, Leopoldo Soares

    2013-01-01

    Background The adipose tissue is considered not only a storable energy source, but mainly an endocrine organ that secretes several cytokines. Adiponectin, a novel protein similar to collagen, has been found to be an adipocyte-specific cytokine and a promising cardiovascular risk marker. Objectives To evaluate the association between serum adiponectin levels and the risk for cardiovascular events in patients with acute coronary syndromes (ACS), as well as the correlations between adiponectin and metabolic, inflammatory, and myocardial biomarkers. Methods We recruited 114 patients with ACS and a mean 1.13-year follow-up to measure clinical outcomes. Clinical characteristics and biomarkers were compared according to adiponectin quartiles. Cox proportional hazard regression models with Firth's penalization were applied to assess the independent association between adiponectin and the subsequent risk for both primary (composite of cardiovascular death/non-fatal acute myocardial infarction (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular death/non-fatal AMI/non-fatal stroke/ rehospitalization requiring revascularization). Results There were significant direct correlations between adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and significant inverse correlations between adiponectin and waist circumference, body weight, body mass index, Homeostasis Model Assessment (HOMA) index, triglycerides, and insulin. Adiponectin was associated with higher risk for primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p = 0.01 and p = 0.02, respectively). Conclusion In ACS patients, serum adiponectin was an independent predictor of cardiovascular events. In addition to the anthropometric and metabolic correlations, there was a significant direct correlation between adiponectin and BNP. PMID:24029961

  5. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain. PMID:26490459

  6. CEACAM1 and MICA as novel serum biomarkers in patients with acute and recurrent pericarditis

    PubMed Central

    Markel, Gal; Imazio, Massimo; Koren-Morag, Nira; Galore-Haskel, Gilli; Schachter, Jacob; Besser, Michal; Cumetti, Davide; Maestroni, Silvia; Altman, Arie; Shoenfeld, Yehuda; Brucato, Antonio; Adler, Yehuda

    2016-01-01

    Background The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function. Methods and results Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ∼50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality. Conclusions Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies. PMID:26909604

  7. [Usefulness of serum cardiac myosin light chain I for the estimation of acute myocardial infarction size].

    PubMed

    Narita, M; Kurihara, T; Murano, K; Usami, M

    1991-09-01

    To evaluate the usefulness of serum level of cardiac myosin light chain I (LC I) for the estimation of the extent of acute myocardial infarction (AMI), peak LC I level was compared with myocardial infarction weight (AMI weight) which was obtained by myocardial emission tomography with Tc-99m pyrophosphate (PYP). In 11 patients with AMI, serum LC I levels were measured once a day in most cases, and plasma CPK levels were measured serially (every 4 hours at least 48 hours after admission). Tc-99m PYP imagings were performed at second or third day of AMI, and AMI weight was calculated from the voxel numbers of myocardial hot spot in which Tc-99m PYP had accumulated. Peak LC I level correlated well with AMI weight (r = 0.72, p less than 0.02). As well as peak LC I level, peak CPK level correlated well with AMI weight (r = 0.68, p less than 0.05). But the estimation of the infarct size from peak LC I level had the following advantages over the estimation from peak CPK level. 1) We could compare peak LC I level with AMI weight in all 11 patients, but peak CPK level was able to compared with AMI weight in only 9 of them. This was because CPK level changed rapidly and reached maximum within 24 hours after the onset of AMI, while LC I level peaked after 3 to 5 days. 2) A good correlation between LC I and AMI weight was obtained by the determination of serum LC I level once a day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1836269

  8. Acute phase protein response in the capybara (Hydrochoerus hydrochaeris).

    PubMed

    Bernal, Luis; Feser, Mariane; Martínez-Subiela, Silvia; García-Martínez, Juan D; Cerón, José J; Tecles, Fernando

    2011-10-01

    We evaluated the acute phase protein response in capybaras (Hydrochoerus hydrochaeris). Three animal groups were used: 1) healthy animals (n=30), 2) a group in which experimental inflammation with turpentine was induced (n=6), and 3) a group affected with sarcoptic scabies (n=14) in which 10 animals were treated with ivermectin. Haptoglobin (Hp), acid-soluble glycoprotein (ASG) and albumin were analyzed in all animals. In those treated with turpentine, Hp reached its maximum value at 2 wk with a 2.7-fold increase, whereas ASG increased 1.75-fold and albumin decreased 0.87-fold 1 wk after the induction of inflammation. Capybaras affected with sarcoptic scabies presented increases in Hp and ASG of 4.98- and 3.18-fold, respectively, and a 0.87-fold decrease in albumin, compared with healthy animals. Haptoglobin and ASG can be considered as moderate, positive acute phase proteins in capybaras because they showed less than 10-fold increases after an inflammatory process and reached their peak concentrations 1 wk after the induction of inflammation. Conversely, albumin can be considered a negative acute phase protein in capybaras because it showed a reduction in concentration after inflammatory stimulus. PMID:22102653

  9. Normal Caloric Responses during Acute Phase of Vestibular Neuritis

    PubMed Central

    Lee, Sun-Uk; Park, Seong-Ho; Kim, Hyo-Jung; Koo, Ja-Won

    2016-01-01

    Background and Purpose We report a novel finding of caloric conversion from normal responses into unilateral paresis during the acute phase of vestibular neuritis (VN). Methods We recruited 893 patients with a diagnosis of VN at Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to 2014 after excluding 28 patients with isolated inferior divisional VN (n=14) and those without follow-up tests despite normal caloric responses initially (n=14). We retrospectively analyzed the neurotological findings in four (0.5%) of the patients who showed a conversion from initially normal caloric responses into unilateral paresis during the acute phase. Results In those four patients, the initial caloric tests were performed within 2 days of symptom onset, and conversion into unilateral caloric paresis was documented 1–4 days later. The clinical and laboratory findings during the initial evaluation were consistent with VN in all four patients except for normal findings in bedside head impulse tests in one of them. Conclusions Normal findings in caloric tests should be interpreted with caution during the acute phase of suspected VN. Follow-up evaluation should be considered when the findings of the initial caloric test are normal, but VN remains the most plausible diagnosis. PMID:26932259

  10. The acute phase protein haptoglobin regulates host immunity

    PubMed Central

    Huntoon, Kristin M.; Wang, Yanping; Eppolito, Cheryl A.; Barbour, Karen W.; Berger, Franklin G.; Shrikant, Protul A.; Baumann, Heinz

    2008-01-01

    The contribution of acute phase plasma proteins to host immune responses remains poorly characterized. To better understand the role of the acute phase reactant and major hemoglobin-binding protein haptoglobin (Hp) on the function of immune cells, we generated Hp-deficient C57BL/6J mice. These mice exhibit stunted development of lymphoid organs associated with lower counts of mature T and B cells in the blood and secondary lymphoid compartments. Moreover, these mice show markedly reduced adaptive immune responses as represented by reduced accumulation of IgG antibody after immunization with adjuvant and nominal antigen, abrogation of Th1-dominated delayed-type hypersensitivity reaction, loss of mitogenic responses mounted by T cells, and reduced T cell responses conveyed by APCs. Collectively, these defects are in agreement with the observations that Hp-deficient mice are not capable of generating a recall response or deterring a Salmonella infection as well as failing to generate tumor antigen-specific responses. The administration of Hp to lymphocytes in tissue culture partially ameliorates these functional defects, lending further support to our contention that the acute phase response protein Hp has the ability to regulate immune cell responses and host immunity. The phenotype of Hp-deficient mice suggests a major regulatory activity for Hp in supporting proliferation and functional differentiation of B and T cells as part of homeostasis and in response to antigen stimulation. PMID:18436583

  11. Sex differences in acute hormonal and subjective response to naltrexone: the impact of menstrual cycle phase

    PubMed Central

    Roche, Daniel J.O.; King, Andrea C.

    2015-01-01

    Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n = 46 women) participated in two morning sessions in which they received 50 mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n = 23) or luteal phase of the MC. Serum cortisol, prolactin, and luteinizing hormone (LH), salivary cortisol, and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women. PMID:25459893

  12. Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase.

    PubMed

    Roche, Daniel J O; King, Andrea C

    2015-02-01

    Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n=46 women) participated in two morning sessions in which they received 50mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n=23) or luteal phase of the MC. Serum cortisol, salivary cortisol, prolactin, luteinizing hormone (LH), and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women. PMID:25459893

  13. The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms.

    PubMed

    Ruiz-González, Agustín; Utrillo, Laia; Bielsa, Silvia; Falguera, Miquel; Porcel, José M

    2016-01-01

    Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p < 0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82-0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms. PMID:27610265

  14. The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms

    PubMed Central

    Utrillo, Laia; Bielsa, Silvia; Falguera, Miquel; Porcel, José M.

    2016-01-01

    Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p < 0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82–0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms. PMID:27610265

  15. Lack of association of acute phase response proteins with hormone levels and antidepressant medication in perimenopausal depression

    PubMed Central

    2014-01-01

    Background Major depression is associated with higher plasma levels of positive acute-phase proteins, as well as with lower plasma levels of negative acute-phase proteins. The aim of this study is to examine the levels of acute-phase response proteins and whether these levels are influenced by reproductive hormones and antidepressant medication in the perimenopausal depression. Methods Sixty-five women (age range: 40–58 years old) participated in this study. All women were in the perimenopausal phase. The diagnosis of depression was made through a psychiatric interview and with the aid of Hamilton Depression Rating Scale 17 (HAM-D 17). The acute-phase response proteins, such as haptoglobin (HP), transferrine (TRf), α1-antitrypsin, complement protein 3 (C3), complement protein 4 (C4) and C-reactive protein (CRP) and the reproductive hormones, for example follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), were analyzed using standard laboratory methods. Pearson’s correlations were applied to evaluate the relationship between acute-phase proteins and hormones. Results Perimenopausal women were divided into three groups. The first group consisted of normal controls, the second one involved depressed perimenopausal women, who were taking selective serotonin reuptake inhibitors (SSRIs), and the third one included depressed women that were not treated with SSRIs. Depressed women in perimenopause, when being compared to non-depressed women, did not differ as to serum levels of acute-phase proteins. There was a positive correlation between HP and E2 in depressed perimenopausal women, who were not taking SSRIs. Conclusions The lack of association between acute-phase proteins and depressive mood mentioned in this study does not support previous findings in patients with major depression. This negative finding in perimenopausal depression indicates either the absence or a more complex nature of the interactions between acute-phase proteins

  16. [The influence of local and combined acute suppurative Highmore maxillary sinusitis on the serum lactoferrin and interleukin-8 levels in the children].

    PubMed

    Klimova, I I; Zorina, V N; Zorina, R M; Akhtiamov, D R; Zorin, N A

    2014-01-01

    The objective of the present study was to estimate the influence of isolated and combined acute suppurative Highmore maxillary sinusitis on the serum lactoferrin (LF) and interleukin-8 (IL-8) levels in the children. A total of 70 children at the age varying from 4 to 15 years were available for the examination. Twenty of them constituted the control group, 29 presented with acute suppurative Highmore maxillary sinusitis, in 21 cildren this condition was combined with frontitis, ethmoiditis, otitis, and adenoiditis. Serum lactoferrin and interleukin-8 levels were measured by solid phase enzyme-linked immunoassay. It was shown that all the aforementioned forms of rhinosinusitis were associated with a significant increase of the serum LF level, an universal factor inactivating the propagation of bacterial, viral, and fungal pathogens. The level of IL-8 known to activate chemotaxis was increased only in the children presenting with combined forms of suppurative Highmore maxillary sinusitis. It is concluded that this difference can be used for the purpose of dufferential diagnostics of different forms of suppurative maxillary sinusitis. PMID:25588485

  17. Acute effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in sedentary young women.

    PubMed

    Imamura, H; Katagiri, S; Uchid, K; Miyamoto, N; Nakano, H; Shirota, T

    2000-12-01

    1. The aim of the present study was to examine the effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in seven sedentary young women under controlled conditions. 2. The subjects exercised on separate days for 30 or 60 min at an intensity of 60% of maximal oxygen uptake on a cycle ergometer. Total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), HDL2-C, HDL3-C, low-density lipoprotein-cholesterol, apolipoproteins A-I, A-II and B were measured in the serum at the end of the 60 min rest period before each exercise, immediately after the performance of each exercise and at 30 min and 1, 2 and 24 h after each exercise. 3. The results showed that there were no significant differences between the pre- and postexercise samples for any of the parameters tested. 4. The results of the present study suggest that a single bout of exercise designed to simulate a typical training workout has no noticeable effect on serum lipids, lipoproteins and apolipoproteins in normal sedentary young women who have normal lipid profiles, are in the follicular phase of their menstrual cycle and who consume a relatively low-fat diet. PMID:11117233

  18. Changes of serum amylase, its isozyme fractions and amylase-creatinine clearance ratio in dogs with experimentally induced acute pancreatitis.

    PubMed

    Akuzawa, M; Morizono, M; Nagata, K; Hayano, S; Sakamoto, H; Yasuda, N; Okamoto, K; Kawasaki, Y; Deguchi, E

    1994-04-01

    To investigate the diagnostic application of amylase to canine pancreatic diseases, serum amylase activities, its isozyme fractions and amylase-creatinine clearance ratio (ACCR) were analyzed in normal intact dogs and dogs experimentally induced acute pancreatitis. There was no statistic difference between normal male and female dogs. Amylase specific activities in pancreatic tissue extracts were more than 2,300 times higher than that in serum, and were also higher than those in other tissues; parotid and mandibular salivary glands, lung, heart, liver, spleen, duodenum, jejunum, ileum and kidney. Following the chloroform injection into the pancreatic tissue, WBC increased from 6 to 240 hr and serum glucose significantly increased at 72 and 96 hr, and no urine glucose was detected. BUN as well as serum and urine creatinine showed normal levels. ACCR increased until 96 hr without statistic significance. Serum amylase activities increased significantly after 3 hr and its isozyme was separated into 4 fractions (Amy1-Amy4) in contrast to 3 fractions (Amy2-Amy4) in intact dogs. Since this extra Amy1 seen from 1 hr increasing after 6 hr similarly to other 3 fractions, the evaluation of serum amylase and its isozyme fractions was indicated to be useful for the diagnosis of acute pancreatitis in dogs. PMID:7521216

  19. Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients.

    PubMed

    Perini, F; Morra, M; Alecci, M; Galloni, E; Marchi, M; Toso, V

    2001-08-01

    The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=-0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the antiinflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients. PMID:11808851

  20. Fever and increased serum IL-1 activity as a systemic manifestation of acute phototoxicity in New Zealand White rabbits.

    PubMed

    Ansel, J C; Luger, T A; Green, I

    1987-07-01

    Ultraviolet (UV) radiation is a significant environmental hazard for humans and animals. Although the clinical effect of an acute UV exposure such as cutaneous inflammation, malaise, somnolence, chills, and fever have been appreciated for many years, the underlying mechanisms mediating these effects are poorly understood. Since chills and fever are the most dramatic systemic sequelae after a prolonged exposure to UV, we specifically examined the effect of whole-body UV irradiation on core body temperature and serum endogenous pyrogen activity of New Zealand White rabbits, correlating this with serum interleukin 1 (IL-1) activity and alterations of serum divalent cation levels. We found that an acute dose of UV irradiation (Westinghouse FS-40 lamps, 0.2 mJ/cm2/s X 8 h) resulted in a significant increase in the core body temperature 2 h post UV (0.8 degree C), peaking 5 h post UV (1.8 degree C), and returning to normal 24 h post UV. Likewise, the sera from the UV-irradiated rabbits had significant endogenous pyrogen activity when transferred into naive recipient animals, causing an increase in core body temperature within 45 min (0.65 +/- 0.12 degree C), decreasing over the next 2 h, and returning to normal 6 h post injection. No endotoxin contamination was detected in any serum samples. This post-UV febrile response was accompanied by a prolonged increase in serum IL-1 activity (5-10 X) and a significant alteration in serum divalent cation levels, with the rabbits becoming euthermic even as the serum IL-1 levels remained elevated. These findings provide new information concerning the pathogenesis and kinetics of these systemic effects after an acute dose of UV irradiation. PMID:3496401

  1. Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

    PubMed Central

    Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov; Magnusson, Nils E; Moestrup, Søren K; Vilstrup, Hendrik; Grønbæk, Henning

    2016-01-01

    AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate (0.02 mg/kg) or free dexamethasone (0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide (LPS) (2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6) 2 h post-LPS and liver mRNAs and serum concentrations of the rat acute phase protein α-2-macroglobulin (α-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects. RESULTS: The conjugate halved the α-2-M liver mRNA (3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein (201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver mRNA or serum levels of α-2-M. Also, the conjugate reduced TNF-α (7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6 (15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight (421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group. CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo. PMID:27330681

  2. Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

    PubMed Central

    Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2016-01-01

    Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

  3. Serum homocysteine as a risk factor for carotid intimal thickening in acute stroke: A cross sectional observational study

    PubMed Central

    Devasia, Anup J.; Joy, Binu; Tarey, Subhash D.

    2016-01-01

    Introduction: The present study aimed to analyse if there is a correlation between carotid intima medial thickening (CIMT) and Hcy in stroke patients. Methodology: We studied 100 consecutive cases of acute anterior circulation strokes at St. John's Medical College, Bangalore, India. Fasting serum samples for homocysteine were sent within 24 hours of admission and all patients underwent a carotid Doppler scan and carotid intima-medial thickness (CIMT) was estimated on both sides. Results: There was significant correlation between serum homocysteine levels and carotid intima-medial thickness (r = 0.409, p = 0.000). Also after controlling for other possible risk factors it was found that elevations in serum homocysteine levels would cause a variation of 60% in the carotid intima-medial thickening. Conclusion: Serum Hcy levels correlate well with CIMT and hence may predict atherothrombotic events. PMID:27011628

  4. Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels

    PubMed Central

    Grammatikos, Georgios; Dietz, Julia; Ferreiros, Nerea; Koch, Alexander; Dultz, Georg; Bon, Dimitra; Karakasiliotis, Ioannis; Lutz, Thomas; Knecht, Gaby; Gute, Peter; Herrmann, Eva; Zeuzem, Stefan; Mavromara, Penelope; Sarrazin, Christoph; Pfeilschifter, Josef

    2016-01-01

    Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations. PMID:27304952

  5. Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels.

    PubMed

    Grammatikos, Georgios; Dietz, Julia; Ferreiros, Nerea; Koch, Alexander; Dultz, Georg; Bon, Dimitra; Karakasiliotis, Ioannis; Lutz, Thomas; Knecht, Gaby; Gute, Peter; Herrmann, Eva; Zeuzem, Stefan; Mavromara, Penelope; Sarrazin, Christoph; Pfeilschifter, Josef

    2016-01-01

    Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations. PMID:27304952

  6. Aberrant serum polyunsaturated fatty acids profile is relevant with acute coronary syndrome.

    PubMed

    Sakamoto, Atsushi; Saotome, Masao; Hosoya, Natsuko; Kageyama, Shigetaka; Yoshizaki, Toru; Takeuchi, Ryosuke; Murata, Koichiro; Nawada, Ryuzo; Onodera, Tomoya; Takizawa, Akinori; Satoh, Hiroshi; Hayashi, Hideharu

    2016-08-01

    Although a robust relationship between aberrant serum polyunsaturated fatty acids (PUFAs) profile and coronary artery disease (CAD) has been reported, the details concerning the association between aberrant PUFAs profile and clinical feature of CAD are not fully discovered. Therefore, we investigated the relationship between serum PUFAs and clinical profiles in CAD patients. We classified 595 consecutive CAD patients, who underwent coronary angiography into 3 groups according to the clinical profiles of CAD (group A: early phase ACS, n = 96; group B: stable CAD with previous history of ACS, n = 259; group C: stable CAD without previous history of ACS, n = 240) and measured serum n-3 [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and n-6 [arachidonic acid (AA)] PUFAs. Serum EPA, DHA, and EPA/AA ratio were significantly low in the order of group A < B < C [EPA; 48.1 (34.1-60.3) μg/ml, 61.7 (41.2-94.5) μg/ml, and 74.4 (52.7-104.9) μg/ml, DHA; 113.1 (92.8-135.1) μg/ml, 125.8 (100.4-167.2) μg/ml, and 140.1 (114.7-177.0) μg/ml, EPA/AA ratio; 0.31 (0.22-0.45), 0.39 (0.26-0.62), and 0.44 (0.31-0.69), medians with interquartile range, p < 0.01]. Multiple regression analysis revealed that EPA (p = 0.009) and EPA/AA ratio (p = 0.023), but not DHA and DHA/AA ratio, were negatively associated with clinical profiles of ACS in CAD patients. Significant correlation was not observed between PUFAs profile and severity of coronary stenosis. Low serum EPA and EPA/AA ratio correlates with clinical profiles of ACS in patients with CAD, regardless of the extent and severity of coronary artery stenosis. PMID:26233644

  7. Serum thyroid autoantibodies in patients with idiopathic either acute or chronic urticaria.

    PubMed

    Gangemi, S; Saitta, S; Lombardo, G; Patafi, M; Benvenga, S

    2009-02-01

    In Italy, only one study was conducted on the detection of serum thyroid autoantibodies (ATA) in patients with urticaria. This northern-Italy study reported a 23% rate of ATA positiveness in 52 patients with chronic idiopathic urticaria (CIU). During the years 1998-2006, 688 patients with urticaria were hospitalized at our Division of Allergy and Clinical Immunology. Thyroglobulin and thyroperoxidase autoantibodies (TgAb and TPOAb) were assayed at admission in 144/688 patients. Of the 144 patients (mean age: 42.3+/-15.8 yr, range 17-84), 95 (72 women and 23 men) had an history of CIU (CIU group) and 49 (44 women and 5 men) did not [acute urticaria group or (AU)]. Of the 144 patients, 37 (25.7%) tested positive for at least one ATA: 31 with CIU (32.6%) and 6 with AU (12.2%, chi2=7.037, p=0.008). Positiveness for TPOAb or TgAb was 30/37 (81.1%) or 17/37 (45.9%); 10/37 (27.0%). Pre-hospitalization duration of CIU was longer in the 31 ATA positive patients compared to the 64 ATA negative patients (207.2+/-273.4 vs 81.6+/-106.3 weeks, p=0.015). Pre-hospitalization duration of CIU correlated positively with the log10-transformed serum concentration of TPOAb in the 25 CIU patients who tested TPOAb positive (r=0.42, p=0.039). We conclude that our rate of 31/95 (32.6%) positiveness for at least one type of ATA in CIU is greater than that of 6 representative international studies published between the years 2000 and 2006 (111/488 or 22.7%, range 15-29%, chi2=4.884, p=0.027). PMID:19411805

  8. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers.

    PubMed

    Kjell, Jacob; Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew; Olson, Lars

    2015-11-01

    With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines--monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)--to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  9. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  10. Serum biomarkers and source of inflammation in acute coronary syndromes and percutaneous coronary interventions.

    PubMed

    Centurión, Osmar Antonio

    2016-03-01

    There is robust information that confirms the enormous contribution of inflammation to plaque development, progression and vulnerability. The presence of plaques with inflammatory components associates with a greater likelihood of future cardiovascular events. The inflammatory cascade has been implicated during the entire plaque formation, from the early stages of endothelial dysfunction to the development of acute coronary syndromes (ACS). The presence of macrophages, T lymphocytes, dendritic cells, and mast cells in atherosclerotic lesions; the detection of HLA class II antigen expression; and the finding of secretion of several cytokines point to the involvement of immune inflammatory mechanisms in the pathogenesis of atherosclerosis. Serum biomarkers reflecting the activity of biological processes involved in plaque growth or destabilization may provide great help in establishing the appropriate clinical management, and therapeutic interventions. Evidence for a role of inflammation in plaque rupture has been demonstrated by localization of inflammation at plaque rupture sites. However, the focus of inflammation may not precisely reside within the coronary vessel itself but rather in the injured myocardium distal to the disrupted plaque. These observations outline the potential benefits of therapies targeting inflammation in the arterial wall and cardiovascular system. Emerging anti-inflammatory approaches to vascular protection have the potential to benefit patients by marked reductions in serum biomarkers of inflammation and reduce vascular events. With ongoing technical advances, percutaneous coronary interventions (PCI) will continue to play a critical role in the evaluation of novel compounds designed to modulate inflammation. The constant refinements in the different therapeutic strategies, the combination of scientific understanding in the adequate utilization of novel inflammatory markers, the new pharmacologic agents, and the new techniques in PCI will

  11. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

    PubMed Central

    Vujasinovic, Miroslav; Tepes, Bojan; Makuc, Jana; Rudolf, Sasa; Zaletel, Jelka; Vidmar, Tjasa; Seruga, Maja; Birsa, Bostjan

    2014-01-01

    AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria. RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks. CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful. PMID:25561813

  12. Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

    PubMed Central

    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is

  13. The Effect of Oxandrolone on the Endocrinologic, Inflammatory, and Hypermetabolic Responses During the Acute Phase Postburn

    PubMed Central

    Jeschke, Marc G.; Finnerty, Celeste C.; Suman, Oscar E.; Kulp, Gabriela; Mlcak, Ronald P.; Herndon, David N.

    2007-01-01

    Objective and Summary Background Data: Postburn long-term oxandrolone treatment improves hypermetabolism and body composition. The effects of oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. Methods: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus oxandrolone for at least 7 days (oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. Results: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in oxandrolone-treated patients (0.48 ± 0.02 days/% burn) compared with controls (0.56 ± 0.02 days/% burn), (P < 0.05). Control patients lost 8 ± 1% of their lean body mass (LBM), whereas oxandrolone-treated patients had preserved LBM (+9 ± 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased α2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. Conclusions: In this large prospective, double-blinded, randomized single-center study, oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT. PMID:17717439

  14. Fever and acute phase reactants in the rat.

    PubMed Central

    van Vugt, H.; van Gool, J.; Deutz, N. E.

    1988-01-01

    In rats synthesis of some acute phase reactants can be induced by a combination of corticosteroids and adrenaline. During fever both hormones show high plasma levels. We studied the effect of fever induced by intra-cerebroventricular (i.c.v.) injection of PGE2 on the acute phase response. Fever was continuously recorded and 24 h after induction acute phase reactant (APR) response was measured as indicated by the rise of alpha-macrofetoprotein (alpha M FP, alpha 2 macroglobulin of the rat). Controls received 0.9% saline i.c.v. Controls did not develop fever (dTmax less than or equal to 1 degree C) nor did they show significant APR response. The maximal rise in body temperature after PGE2 (2.6 +/- 0.7 degrees C) correlated significantly with the rise in alpha M FP concentration 24 h later. Adrenalectomy prevented the APR response completely but the magnitude of the fever reaction remained the same (2.1 +/- 0.3 degrees C). alpha-Blockade gave a smaller fever response but had no effect on the APR response. In alpha- and beta-blockade, fever response was normal but no APR response was obtained. Destroying the sympathetic nerve supply to the liver with 6-OH dopamine retarded the fever response but again APR response was not impeded. In order to differentiate between the role of fever as such and the effect of PGE2 on APR synthesis, we used heat exposure to induce hyperthermia in normal rats who showed an APR response comparable with that after i.c.v. PGE2. Pretreatment with sodium salicylate before inducing hyperthermia led to a variable rise in alpha M FP. Fever as such, without tissue injury, induces an APR response. The pathway to this effect probably involves circulating corticosterone and adrenaline, possibly via a beta-receptor mediated stimulation. PMID:2460123

  15. Induction of hepatocyte lipopolysaccharide binding protein in models of sepsis and the acute-phase response.

    PubMed

    Geller, D A; Kispert, P H; Su, G L; Wang, S C; Di Silvio, M; Tweardy, D J; Billiar, T R; Simmons, R L

    1993-01-01

    Lipopolysaccharide binding protein (LBP) is a serum glycoprotein that complexes with lipopolysaccharide (LPS) to facilitate macrophage response to endotoxin. To determine the conditions that stimulate LBP production in vivo, we measured the induction of LBP in models of inflammation produced by LPS, Corynebacterium parvum, and turpentine injection. Plasma aspartate aminotransferase and alanine aminotransferase concentrations and hepatocyte fibrinogen synthesis were elevated in all models. Northern blot analysis revealed 17-, 14-, and 20-fold upregulation of hepatocyte LBP mRNA following treatment with LPS, C parvum, and turpentine, respectively. Peritoneal macrophage interleukin 6 and tumor necrosis factor production following endotoxin stimulation was augmented by cultured hepatocyte supernatants, suggesting increased LBP synthesis in these groups. The results show that LBP mRNA is induced during hepatic inflammation and suggest that LBP is an acute-phase protein important in regulating the in vivo response to endotoxin. PMID:8418776

  16. The silk protein, sericin, protects against cell death caused by acute serum deprivation in insect cell culture.

    PubMed

    Takahashi, Masakazu; Tsujimoto, Kazuhisa; Yamada, Hideyuki; Takagi, Hiroshi; Nakamori, Shigeru

    2003-11-01

    Sericin is the silk protein that covers fibroin fibers and functions as a 'glue' in the cocoons of silkworms, and its most abundant component, Ser1, contains repeats of Ser- and Thr-rich 38 amino acid residues. The viability of Sf9 insect cells was 20, 57 and 49% on the fifth day and 41, 91 and 70% on the ninth day after serum deprivation in the presence of no additives, 3000 microg sericin hydrolysate and 350 microg SerD (the peptide containing the two repetitive units) ml(-1), respectively. Thus, the sericin samples were useful in preventing cell death and promoting cellular growth after acute serum deprivation. PMID:14677702

  17. Tail biting induces a strong acute phase response and tail-end inflammation in finishing pigs.

    PubMed

    Heinonen, Mari; Orro, Toomas; Kokkonen, Teija; Munsterhjelm, Camilla; Peltoniemi, Olli; Valros, Anna

    2010-06-01

    The extent of inflammation associated with tail biting in finishing pigs was evaluated. Tail histopathology, carcass condemnation and the concentration of three acute phase proteins (APPs), C-reactive protein (CRP), serum amyloid-A (SAA) and haptoglobin (Hp), were examined in 12 tail-bitten and 13 control pigs. The median concentrations of APPs were higher (P<0.01) in bitten (CRP 617.5mg/L, range 80.5-969.9; SAA 128.0mg/L, 6.2-774.4; Hp 2.8g/L, 1.6-3.5) than in control pigs (CRP 65.7mg/L, 28.4-180.4; SAA 6.2mg/L, 6.2-21.4; Hp 1.2g/L, 0.9-1.5). There was a tendency for APP concentrations to rise with the histopathological score but the differences were only statistically significant between some of the scores. Five (42%) bitten cases and one (8%) control pig had partial carcass condemnations owing to abscesses (P=0.07). The results show that tail biting induces an inflammatory response in the tail end leading to an acute phase response and formation of carcass abscesses. PMID:19398209

  18. Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction.

    PubMed

    Magga, Jarkko; Puhakka, Mikko; Hietakorpi, Seppo; Punnonen, Kari; Uusimaa, Paavo; Risteli, Juha; Vuolteenaho, Olli; Ruskoaho, Heikki; Peuhkurinen, Keijo

    2004-04-01

    Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH(2)-terminal proANP (r = 0.45, P < 0.001), BNP (r = 0.55, P < 0.001) and NH(2)-terminal proBNP (r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% (P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% (P < 0.001). ICTP levels correlated with NH(2)-terminal proBNP (r = 0.25, P < 0.05) and BNP (r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP. PMID:14607848

  19. Assessment of Serum UCH-L1 and GFAP in Acute Stroke Patients

    PubMed Central

    Ren, Changhong; Kobeissy, Firas; Alawieh, Ali; Li, Na; Li, Ning; Zibara, Kazem; Zoltewicz, Susie; Guingab-Cagmat, Joy; Larner, Stephen F.; Ding, Yuchuan; Hayes, Ronald L.; Ji, Xunming; Mondello, Stefania

    2016-01-01

    A rapid and reliable diagnostic test to distinguish ischemic from hemorrhagic stroke in patients presenting with stroke-like symptoms is essential to optimize management and triage for thrombolytic therapy. The present study measured serum concentrations of ubiquitin C-terminal hydrolase (UCH-L1) and glial fibrillary astrocytic protein (GFAP) in acute stroke patients and healthy controls and investigated their relation to stroke severity and patient characteristics. We also assessed the diagnostic performance of these markers for the differentiation of intracerebral hemorrhage (ICH) from ischemic stroke (IS). Both UCH-L1 and GFAP concentrations were significantly greater in ICH patients than in controls (p < 0.0001). However, exclusively GFAP differed in ICH compared with IS (p < 0.0001). GFAP yielded an AUC of 0.86 for differentiating between ICH and IS within 4.5hrs of symptom onset with a sensitivity of 61% and a specificity of 96% using a cut-off of 0.34ng/ml. Higher GFAP levels were associated with stroke severity and history of prior stroke. Our results demonstrate that blood UCH-L1 and GFAP are increased early after stroke and distinct biomarker-specific release profiles are associated with stroke characteristics and type. We also confirmed the potential of GFAP as a tool for early rule-in of ICH, while UCH-L1 was not clinically useful. PMID:27074724

  20. [Changes of endotoxin concentration in blood serum in patients with uncomplicated acute myocardial Q-infarction].

    PubMed

    Anikhovskaya, I A; Kubatiev, A A; Salakhov, I M; Tebloev, K I; Yakovlev, M Yu

    2015-01-01

    The effectiveness of acute myocardial infarction (AMI) treatment does not correspond to high material costs for the study of its pathogenesis and development of new drugs. This circumstance gives the grounds to assume existence of nowadays unknown mechanisms of emergence and development of this disease. High probability of participation of endotoxin (ET) in the pathogenesis of AMI was theoretically proved by us for more than a quarter of the century ago, but it's clinical evidence to date is not found yet. As a result of the study a significant increase of endotoxin (ET) concentration in the blood serum of patients with AMI increasing from 1 to 14 day of the disease has been found. In women the concentration of ET was higher than in men. It allows to qualify the EA as a factor probably influencing the known difference in AMI tolerance in men and women. The source of ET were Bacteroides (most often--67.8% of patients), Klebsiella, Pseudomonas, Proteus, Escherichia coli. One or two bacteria more often took part in the development of EA. In 9.1% of patients the etiology of EA could not be verified, what indicates the presence of other sources of EA, not evaluated in this study. In 25% of patients with AMI serologic evidence of systemic candidiasis, caused by candida Albicans, has been found, what is able to enhance the biological effects of ET. PMID:26852597

  1. Diminished acute phase response and increased hepatic inflammation of aged rats in response to intraperitoneal injection of lipopolysaccharide.

    PubMed

    Gomez, Christian R; Acuña-Castillo, Claudio; Pérez, Claudio; Leiva-Salcedo, Elías; Riquelme, Denise M; Ordenes, Gamaliel; Oshima, Kiyoko; Aravena, Mauricio; Pérez, Viviana I; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

    2008-12-01

    Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, alpha-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult. PMID:19126842

  2. Periparturient cortisol, acute phase cytokine, and acute phase protein profiles of gilts housed in groups or stalls during gestation.

    PubMed

    Sorrells, A D; Eicher, S D; Harris, M J; Pajor, E A; Richert, B T

    2007-07-01

    Use of gestation stalls in pork production remains a controversial topic in animal welfare. Immune status and measures are frequently used to assess stress levels and thus well-being of confined animals. The important welfare issue of close confinement among gestating gilts was tested by quantifying cortisol, acute phase cytokine, and acute phase protein pro-files before and after farrowing of gilts housed in 2 systems. Landrace x Yorkshire crossbred gilts housed in groups of 4 (group, n = 8) in pens (3.9 x 2.4 m with 4 individual feeding spaces, 9.36 m(2) total or 2.34 m(2)/gilt) were compared with gilts housed in standard industry stalls (stall, n = 16; 2.2 x 0.6 m, 1.32 m(2)/gilt). Floors were fully slatted, and a substrate was not provided for either system. Cortisol was determined from saliva on d 105 of gestation, 1 h after moving the gilts into farrowing stalls (d 111), and 24 h and 7 d after farrowing. Cortisol was greater (P = 0.04) for group gilts compared with stall gilts 1 h after moving them into farrowing stalls and 24 h after farrowing. Cortisol concentrations decreased (P = 0.001) over time. Leukocyte mRNA expression of IL-1, IL-1 receptor antagonist, and tumor necrosis factor-alpha was determined by quantitative, reverse transcription PCR on d 35, 63, and 91 of gestation and 72 h after farrowing. Cytokine mRNA expression of peripheral blood mononuclear cells did not differ between housing systems for IL-1, its receptor antagonist, or for tumor necrosis factor-alpha. Acute phase proteins, including fibrinogen, haptoglobin, and alpha(1)-acid glycoprotein were determined for plasma samples taken at d 35, 63, and 91 of gestation and 72 h and 14 d after farrowing. In contrast to cortisol, plasma fibrinogen concentrations increased (P < 0.005) over time. Haptoglobin did not differ between treatments (P > 0.10). Stall gilts tended to have greater (P = 0.07) plasma alpha(1)-acid glycoprotein concentrations than group animals at d 35 of gestation and d 14

  3. The analysis of the acute phase response during the course of Trypanosoma carassii infection in the goldfish (Carassius auratus L.).

    PubMed

    Kovacevic, Nikolina; Hagen, Mariel O; Xie, Jiasong; Belosevic, Miodrag

    2015-11-01

    The expression of genes encoding the acute phase proteins (APP) during the course of Trypanasoma carassii infection in the goldfish was determined using quantitative PCR. Significant changes in the mRNA levels of ceruloplasmin (Cp), C-reactive protein (CRP), transferrin (Tf), hemopexin (Hx) and serum amyloid A (SAA) were observed in the kidney, liver and spleen at various days post infection (dpi). Of the five acute phase protein genes examined, CRP and SAA exhibited the highest expression in the tissues during the acute infection. Cp and Tf were up-regulated throughout the acute course of infection in the liver. During the chronic phase of the infection, APP expression in the liver was similar to that in the non-infected control fish. At 7 dpi, Cp, Tf and Hx were down-regulated in the spleen, and Cp and Tf kidney, but their mRNA levels gradually returned to those of control non-infected fish. In contrast, during the chronic phase of the infection, there was an up-regulation of Cp, Hx and Tf in the spleen, and Tf and SAA in the kidney. The goldfish CRP was cloned and functionally characterized. CRP was differentially expressed in normal goldfish immune cells, with highest expression in monocytes and lowest expression in mature macrophages. A recombinant goldfish CRP (rgfCRP) was generated using prokaryotic expression. rgfCRP enhanced complement-mediated killing of trypanosomes in vitro, and the lysis increased after addition of immune serum. rgfCRP did not affect the production of reactive oxygen and nitrogen intermediates by monocytes and macrophages, respectively. PMID:26116443

  4. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study

    PubMed Central

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-01-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011–2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  5. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study.

    PubMed

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-08-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011-2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  6. Early Acute Kidney Injury based on Serum Creatinine or Cystatin C in Intensive Care Unit after Major Trauma

    PubMed Central

    Zand, Farid; Sabetian, Golnar; Abbasi, Ghasem; Rezaianzadeh, Abbas; Salehi, Alireza; Khosravi, Abbas; Geramizadeh, Bita; Taregh, Shuja Ulhaq; Javadpour, Shohreh

    2015-01-01

    Background: Acute kidney injury (AKI) is a common problem in critically ill patients and is independently associated with increased morbidity and mortality. Recently, serum cystatin C has been shown to be superior to creatinine in early detection of renal function impairment. We compared estimated GFR based on serum cystatin C with estimated GFR based on serum creatinine for early detection of renal dysfunction according to the RIFLE criteria. Methods: During 9 months, three hundred post trauma patients that were referred to the intensive care unit of a referral trauma hospital were recruited. Serum creatinine and serum cystatin C were measured and the estimated GFR within 24 hours of ICU admission was calculated. The primary outcome was the incidence of AKI according to the RIFLE criteria within 2nd to 7th day of admission. Results: During the first week of ICU admission, 21% of patients experienced AKI. After adjusting for major confounders, only the patients with first day’s serum cystatin level higher than 0.78 mg/l were at higher risk of first week AKI (OR=6.14, 95% CI: 2.5-14.7, P<0.001). First day’s serum cystatin C and injury severity score were the major risk factors for ICU mortality (OR=3.54, 95% CI: 1.7-7.4, P=0.001) and (OR=4.6, 95% CI: 1.5-14, P=0.007), respectively. Conclusion: Within 24 hours after admission in ICU due to multiple trauma, high serum cystatin C level may have prognostic value in predicting early AKI and mortality during ICU admission. However, such correlation was not seen neither with creatinine nor cystatin C based GFR. PMID:26538776

  7. Serum cystatin C and chitotriosidase in acute P-407 induced dyslipidemia: Can they serve as potential early biomarkers for atherosclerosis?

    PubMed

    Korolenko, T A; Pisareva, E E; Filyushina, E E; Johnston, T P; Machova, E

    2015-09-01

    In an attempt to better understand potential biomarkers for, and the role of macrophages in, the development of atherosclerosis, the toxicologic, and any therapeutic pharmacologic effects of carboxymethylated β-glucan, gadolinium chloride, and poloxamer 407 were studied in mice for their capacity to perturb serum lipids, cystatin C, and chitotriosidase-1. Gadolinium and carboxymethylated β-glucan dosed separately to control mice had no effect on serum lipids, whereas carboxymethylated β-glucan, but not gadolinium, exerted a significant (p<0.01) and unexpected hypolipidemic effect in poloxamer 407-induced hyperlipidemic mice. An acute hyperlipidemic state (∼4 days), induced with poloxamer 407 administration alone, resulted in a significant (p<0.01) time-dependent decrease and increase in serum cystatin C and chitotriosidase, respectively. Carboxymethylated β-glucan administration to hyperlipidemic mice significantly (p<0.05) increased the serum concentration of cystatin C, but significantly (p<0.01) decreased chitotriosidase activity, when each was compared to mice treated with poloxamer 407 only. Gadolinium administration caused a significant decrease in serum chitotriosidase activity in both controls (p<0.01) and poloxamer 407-induced hyperlipidemic (p<0.001) mice, but had no effect on the concentration of cystatin C in either controls or poloxamer 407-induced hyperlipidemic mice. Gadolinium administration resulted in both morphological and functional changes to liver macrophages, which included incorporation of excess lipids, especially when simultaneously administered with poloxamer 407. It is suggested that serum cystatin C and chitotriosidase may represent potential early biomarkers for eventual atherosclerosis in the poloxamer 407-induced mouse model of atherogenesis, and that two compounds known to either increase (carboxymethylated β-glucan) or decrease (gadolinium chloride) the number of macrophages in vivo were able to modulate serum

  8. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response

    PubMed Central

    Rivory, L P; Slaviero, K A; Clarke, S J

    2002-01-01

    Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A function in 40 patients with advanced cancer using the erythromycin breath test. Both the traditional C20min measure and the recently proposed 1/TMAX values were estimated. The marker of acute-phase response, C-reactive protein and the pro-inflammatory cytokines IL-6, IL-1β, TNFα and IL-8 were measured in serum or plasma at baseline. Cancer patients with an acute phase response (C-reactive protein >10 mg l−1, n=26) had reduced metabolism as measured with the erythromycin breath test 1/TMAX (Kruskal–Wallis Anova, P=0.0062) as compared to controls (C-reactive protein ⩽10 mg l−1, n=14). Indeed, metabolism was significantly associated with C-reactive protein over the whole concentration range of this acute-phase marker (r=−0.64, Spearman Rank Correlation, P<0.00001). C-reactive protein serum levels were significantly correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population. British Journal of Cancer (2002) 87, 277–280. doi:10.1038/sj.bjc.6600448 www.bjcancer.com © 2002 Cancer Research UK PMID:12177794

  9. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    PubMed

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares. PMID:27177966

  10. Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition?

    PubMed

    Alemán, María Remedios; Santolaria, Francisco; Batista, Norberto; de La Vega, María; González-Reimers, Emilio; Milena, Antonio; Llanos, Marta; Gómez-Sirvent, Juan Luis

    2002-07-01

    Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers. These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat. PMID:12200109

  11. Typical Hus: Evidence of Acute Phase Complement Activation from a Daycare Outbreak

    PubMed Central

    Brady, Tammy M; Pruette, Cozumel; Loeffler, Lauren F; Weidemann, Darcy; Strouse, John J; Gavriilaki, Eleni; Brodsky, Robert A

    2016-01-01

    The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by eculizumab in vitro, an effect that was replicated in vitro utilizing Shiga toxin as a stimulus of complement activation in normal serum. Our report suggests that complement blockade may be effective in the treatment of STEC-HUS when initiated early in the disease. Given the epidemic nature of the disease that limits the feasibility of randomized clinical trials, further studies are needed to determine the value of early eculizumab treatment in STEC-HUS. PMID:27413789

  12. Acute phase protein and protein electrophoresis values for captive Grant's zebra (Equus burchelli).

    PubMed

    Cray, Carolyn; Hammond, Elizabeth; Haefele, Holly

    2013-12-01

    Grant's zebra (Equus burchelli) are commonly kept in zoos and are subject to routine health monitoring and research studies. Recently, assays for acute phase proteins (APP) have been described in many wildlife species, and specific assays for serum amyloid A (SAA) have been well validated and studied in horses (Equus ferus caballus), in which it serves as a major APP. In the present study, serum samples from 26 Grant's zebra were subject to analysis by using assays for SAA, haptoglobin (HP), and protein electrophoresis. Reference intervals were calculated by using the robust method: SAA 1.8-31.4 mg/L and HP 0.37-1.58 mg/ml. Significant differences in SAA and HP were observed in clinically abnormal zebra; in some cases, these differences were marked and were noted in the absence of abnormal values for protein electrophoretic fractions. These data indicate that APP may be a valuable and sensitive tool in monitoring inflammation in this species. PMID:24450080

  13. Serum Level of Fibroblast Growth Factor 21 Is Independently Associated with Acute Myocardial Infarction

    PubMed Central

    Ding, Wenhui; Wang, Fang

    2015-01-01

    Background Fibroblast growth factor 21 (FGF21) has been described as a metabolic hormone critical for glucose and lipid metabolism. Previously, high levels of FGF21 were observed in patients with coronary heart disease and non-acute myocardial infarction (non-AMI). In this study, we investigated the changes in FGF21 levels in Chinese patients with AMI. Methodology/Principal Findings We used ELISA to measure circulating FGF21 levels in 55 AMI patients and 45 non-AMI control patients on the 1st day after syndrome onset. All patients were followed-up within 30 days. FGF21 levels in AMI patients were significantly higher than those in non-AMI controls (0.25 (0.16–0.34) vs. 0.14 (0.11–0.20) ng/mL, P < 0.001). FGF21 levels reached the maximum within approximately 24 h after the onset of AMI and remained at high for 7 days, and the FGF21 level (OR: 16.93; 95% confidence interval (CI): 2.65–108.05; P = 0.003) was identified as an independent factor associated with the presence of AMI. On the 7th day, FGF21 levels were significantly higher in the patients who subsequently developed re-infarction within 30 days than in the patients who did not develop re-infarction (with vs. without re-infarction: 0.45 (0.22–0.64) vs. 0.21 (0.15–0.29) ng/mL, P = 0.014). Conclusions/Significance The level of serum FGF21 is independently associated with the presence of AMI in Chinese patients. High FGF21 levels might be related to the incidence of re-infarction within 30 days after onset. PMID:26091256

  14. The Use of Dermal Substitutes in Burn Surgery: Acute Phase

    PubMed Central

    Shahrokhi, Shahriar; Anna, Arno; Jeschke, Marc G.

    2013-01-01

    Dermal substitutes are increasingly becoming an essential part of the burn care strategy. During the acute phase of burn treatment, dermal substitutes improve functional and cosmetic results long-term and thus increase quality of life. In the chronic wound setting, dermal substitutes are used to reconstruct and improve burn scars and other defects. Despite some successes in the use of dermal substitutes there are more needs and requirements to further improve outcomes and hence further research is required not only to strengthen scientific evidence regarding their effects but also to develop new technology and products. Dermal substitutes also emerge as pivotal research strategies to develop adequate scaffolds for stem cells, tissue engineering and regenerative medicine applications to obtain long-lasting and scarless artificial skin. This review discusses status-quo of dermal substitutes and novel strategies in the use of dermal substitutes with a focus on burn care. PMID:24393152

  15. Mechanisms of vascular dysfunction in acute phase of Trypanosoma cruzi infection in mice.

    PubMed

    Silva, Josiane F; Capettini, Luciano S A; da Silva, José F P; Sales-Junior, Policarpo; Cruz, Jader Santos; Cortes, Steyner F; Lemos, Virginia S

    2016-07-01

    Vascular disorders have a direct link to mortality in the acute phase of Trypanosoma cruzi infection. However, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. We hypothesize that T. cruzi invades endothelial cells causing dysfunction in contractility and relaxation of the mouse aorta. Immunodetection of T. cruzi antigen TcRBP28 was observed in endothelial cells. There was a decreased endothelial nitric oxide synthase (eNOS)-derived NO-dependent vascular relaxation, and increased vascular contractility accompanied by augmented superoxide anions production. Endothelial removal, inhibition of cyclooxygenase 2 (COX-2), blockade of thromboxane A2 (TXA2) TP receptors, and scavenger of superoxide normalized the contractile response. COX-2, thromboxane synthase, inducible nitric oxide synthase (iNOS), p65 NFκB subunit and p22(phox) of NAD(P)H oxidase (NOX) subunit expressions were increased in vessels of chagasic animals. Serum TNF-α was augmented. Basal NO production, and nitrotyrosine residue expression were increased. It is concluded that T. cruzi invades mice aorta endothelial cells and increases TXA2/TP receptor/NOX-derived superoxide formation. Alongside, T. cruzi promotes systemic TNF-α increase, which stimulates iNOS expression in vessels and nitrosative stress. In light of the heart failure that develops in the chronic phase of the disease, to understand the mechanism involved in the increased contractility of the aorta is crucial. PMID:26988253

  16. Hepatic acute phase proteins--regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-κB-dependent signaling.

    PubMed

    Bode, Johannes G; Albrecht, Ute; Häussinger, Dieter; Heinrich, Peter C; Schaper, Fred

    2012-01-01

    The function of the liver as an important constituent of the immune system involved in innate as well as adaptive immunity is warranted by different highly specialized cell populations. As the major source of acute phase proteins, including secreted pathogen recognition receptors (PRRs), short pentraxins, components of the complement system or regulators of iron metabolism, hepatocytes are essential constituents of innate immunity and largely contribute to the control of a systemic inflammatory response. The production of acute phase proteins in hepatocytes is controlled by a variety of different cytokines released during the inflammatory process with IL-1- and IL-6-type cytokines as the leading regulators operating both as a cascade and as a network having additive, inhibitory, or synergistic regulatory effects on acute phase protein expression. Hence, IL-1β substantially modifies IL-6-induced acute phase protein production as it almost completely abrogates production of acute phase proteins such as γ-fibrinogen, α(2)-macroglobulin or α(1)-antichymotrypsin, whereas production of for example hepcidin, C-reactive protein and serum amyloid A is strongly up-regulated. This switch-like regulation of IL-6-induced acute phase protein production by IL-1β is due to a complex processing of the intracellular signaling events activated in response to IL-6 and/or IL-1β, with the crosstalk between STAT3- and NF-κB-mediated signal transduction being of particular importance. Recent data suggest that in this context complex formation between STAT3 and the p65 subunit of NF-κB might be of key importance. The present review summarizes the regulation of acute phase protein production focusing on the role of the crosstalk of STAT3- and NF-κB-driven pathways for transcriptional control of acute phase gene expression. PMID:22093287

  17. Association of serum uric acid level with mortality and morbidity of patients with acute ST-elevation myocardial infarction

    PubMed Central

    Hajizadeh, Reza; Ghaffari, Samad; Salehi, Rezvanieh; Mazani, Sarvin; Aghavali, Sharmin

    2016-01-01

    Introduction: Investigating the clinical impact of serum uric acid (UA) and its lowering agents on the complications and mortality of acute ST-elevation myocardial infarction (STEMI) can open a new era in STEMI treatment. The aim of this study was to evaluate the effect of on admission serum UA level on the mortality and morbidity of patients admitted with STEMI. Methods: A number of 608 patients with STEMI were enrolled in this study from December 21, 2012 until February 19, 2014. Patients were followed for 20 months. Male to female ratio was 2.53, and the mean age of patients was 62.6±13.4. The relationship between the level of UA and patients’ mortality and morbidity, left ventricular ejection fraction (LVEF), atrial and ventricular arrhythmia was analyzed. Results: Patients with high serum UA level had higher Killip class after STEMI (P=0.001). Mean LVEF was measured to be 39.5±9.6 in normal UA group and 34.6±11.6 in high UA group (P=0.001). In comparison with normal UA group, high UA group had significantly higher cTnI (2.68±0.09 vs 4.09±0.42, respectively, P=0.001), increased blood pressure (P=0.009), and higher atrial fibrillation (AF) occurrence (P=0.03), but no association was seen between ventricular tachycardia and serum UA level. Short term and midterm mortality were not different in two groups (P=0.44 and 0.31, respectively). Conclusion: In the current study, high serum UA level in patients with acute myocardial infarction (MI) was not associated with higher in-hospital or midterm mortality, but it was associated with lower LVEF, higher Killip class, elevated cTnI, creatinine, triglyceride, and higher AF. PMID:27489597

  18. Serum sodium based modification of the MELD does not improve prediction of outcome in acute liver failure

    PubMed Central

    2013-01-01

    Background Acute liver failure (ALF) is a devastating clinical syndrome with a high mortality rate. The MELD score has been implied as a prognostic tool in ALF. Hyponatremia is associated with lethal outcome in ALF. Inclusion of serum sodium (Na) into the MELD score was found to improve its predictive value in cirrhotic patients. Therefore the aim of this study was to determine whether inclusion of serum Na improves the predictive value of MELD in ALF compared to established criteria. Methods In a prospective single center study (11/2006–12/2010), we recruited 108 consecutive ALF patients (64% females / 36% males), who met the criteria defined by the “Acute Liver Failure Study Group Germany”. Upon admission, clinical and laboratory data were collected, King’s College Criteria (KCC), Model of End Stage Liver Disease score (MELD), and serum sodium based modifications like the MELD-Na score and the United Kingdom Model of End Stage Liver Disease score (UKELD) were calculated and area under the receiver operating characteristic curve analyses were performed regarding the prediction of spontaneous recovery (SR) or non-spontaneous recovery (NSR; death or transplantation). Results Serum bilirubin was of no prognostic value in ALF, and Na also failed to predict NSR in ALF. The classical MELD score was superior to sodium-based modifications and KCC. Conclusions We validated the prognostic value of MELD-Na and UKELD in ALF. Classic MELD score calculations performed superior to KCC in the prediction of NSR. Serum Na and Na-based modifications of MELD did not further improve its prognostic value. PMID:23551795

  19. Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants.

    PubMed

    Ricken, Roland; Adli, Mazda; Lange, Claudia; Krusche, Esther; Stamm, Thomas J; Gaus, Sebastian; Koehler, Stephan; Nase, Sarah; Bschor, Tom; Richter, Christoph; Steinacher, Bruno; Heinz, Andreas; Rapp, Michael A; Borgwardt, Stefan; Hellweg, Rainer; Lang, Undine E

    2013-12-01

    In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms. PMID:24018547

  20. Abnormal physiological conditions in acute schizophrenic patients on emergency admission: dehydration, hypokalemia, leukocytosis and elevated serum muscle enzymes.

    PubMed

    Hatta, K; Takahashi, T; Nakamura, H; Yamashiro, H; Endo, H; Fujii, S; Fukami, G; Masui, K; Asukai, N; Yonezawa, Y

    1998-01-01

    This study investigated varieties and incidence of abnormal physiological conditions in acute schizophrenic patients on emergency. Laboratory data obtained prior to treatment from patients, admitted on an emergency basis during an 18-month period, were evaluated retrospectively, as well as demographics and clinical characteristics. Of 259 male acute schizophrenic patients (ICD-10: F2), 6.9% revealed dehydration, a third had hypokalemia and leukocytosis, and two thirds showed elevated serum muscle enzymes. These percentages were statistically significant compared with those of outpatients. In addition, the former three of these conditions in the F2 group were as frequent as those in alcohol and/or psychoactive substance abusers (ICD-10: F1) on emergency admission, although elevated serum muscle enzymes in the F2 group was less frequent than that in the F1 group. In order to prevent these abnormal physiological conditions from worsening and becoming life-threatening, one fourth of the F2 group [dehydration, 6.9%, severe hypokalemia (< 3.0 mEq/l), 2.3%, and markedly elevated serum muscle enzymes (creatine phosphokinase > 1000 IU/l), 16.5%] required medical management such as fluid therapy and various types of monitoring. In cases of a behavioral emergency, laboratory screening and monitoring of urinary output were essential. Due to their lack of cooperation, case history, physical examination, and initial vital signs did not contribute to detection of their medical condition. PMID:9810481

  1. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    PubMed Central

    Saber, Anne T; Halappanavar, Sabina; Folkmann, Janne K; Bornholdt, Jette; Boisen, Anne Mette Z; Møller, Peter; Williams, Andrew; Yauk, Carole; Vogel, Ulla; Loft, Steffen; Wallin, Håkan

    2009-01-01

    Background Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) – or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver. Results Mice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005) 177–182). As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS) intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap) (the murine homologue of Crp) and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3) responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT-PCR. Conclusion Our findings

  2. Acute-phase protein response in pigs experimentally infected with Haemophilus parasuis.

    PubMed

    Martín de la Fuente, A J; Carpintero, R; Rodríguez Ferri, E F; Alava, M A; Lampreave, F; Gutiérrez Martín, C B

    2010-12-01

    The acute-phase protein (APP) response to an infection caused by Haemophilus parasuis, the etiological agent of Glässer's disease in pigs, was characterized measuring serum concentrations of pig major acute-phase protein (pig MAP), haptoglobin (HPT), C-reactive protein (CRP) and apolipoprotein A-I (ApoA-I) in colostrum-deprived pigs. They were divided into six experimental groups: non-immunized control group (I); immunized with a non-commercial bacterin (II); with an OMP-vaccine (III); with a sublethal dose (IV); and with two commercial bacterins (V and VI). All groups were challenged intratracheally with 5 × 10(9)CFU of H. parasuis 37 days after immunisation. The highest levels of the positive APPs (pig MAP, HPT and CRP) and the lowest levels of the negative APPs (ApoA-I) were observed in the animals that died as a consequence of the infection, both those in the non-immunized and in the immunized groups. However, the surviving animals (all of them in groups II, V and VI, two pigs in group III, and three in group IV) showed a minor variation in APP response, mainly on day 1 post-challenge (p.c.), and then tended to recover the initial values. APP response was still less pronounced in the groups of pigs previously immunized with bacterins. In conclusion, APP response can reflect Glässer-disease ongoing, showing a correlation between the severity and duration of the clinical signs and lesions and the magnitude of changes in the APP levels. PMID:19117607

  3. Changes in gene expression of DOR and other thyroid hormone receptors in rat liver during acute-phase response

    PubMed Central

    Baumgartner, Bernhard G.; Naz, Naila; Sheikh, Nadeem; Moriconi, Federico; Ramadori, Giuliano

    2010-01-01

    Non-thyroidal illness is characterized by low tri-iodothyronine (T3) serum level under acute-phase conditions. We studied hepatic gene expression of the newly identified thyroid hormone receptor (TR) cofactor DOR/TP53INP2 together with TRs in a rat model of aseptic abscesses induced by injecting intramuscular turpentine-oil into each hind limb. A fast (4-6 h) decrease in the serum level of free thyroxine and free T3 was observed. By immunohistology, abundant DOR protein expression was detected in the nuclei of hepatocytes and ED-1+ (mononuclear phagocytes), CK-19+ (biliary cells), and SMA+ (mesenchymal cells of the portal tract) cells. DOR signal was reduced with a minimum at 6-12 h after the acute-phase reaction (APR). Immunohistology also showed a similar pattern of protein expression in TRα1 but without a significant change during APR. Transcripts specific for DOR, nuclear receptor co-repressor 1 (NCoR-1), and TRβ1 were down-regulated with a minimum at 6-12 h, whereas expression for TRα1 and TRα2 was slightly and significantly up-regulated, respectively, with a maximum at 24 h after APR was initiated. In cultured hepatocytes, acute-phase cytokines interleukin-1β (IL-1β) and IL-6 down-regulated DOR and TRβ1 at the mRNA level. Moreover, gene expression of DOR and TRs (TRα1, TRα2, and TRβ1) was up-regulated in hepatocytes by adding T3 to the culture medium; this up-regulation was almost completely blocked by treating the cells with IL-6. Thus, TRβ1, NCoR-1, and the recently identified DOR/TP53INP2 are abundantly expressed and down-regulated in liver cells during APR. Their down-regulation is attributable to the decreased serum level of thyroid hormones and most probably also to the direct action of the main acute-phase cytokines. PMID:20949361

  4. Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) Outperforms Serum Creatinine in Detecting Sepsis-Induced Acute Kidney Injury, Experiments on Bilateral Nephrectomy and Bilateral Ureter Obstruction Mouse Models.

    PubMed

    Leelahavanichkul, Asada; Somparn, Poorichaya; Issara-Amphorn, Jiraphorn; Eiam-Ong, Somchai; Avihingsanon, Yingyos; Hirankarn, Nattiya; Srisawat, Nattachai

    2016-05-01

    Serum neutrophil gelatinase associated lipocalin (sNGAL), a promising acute kidney injury (AKI) biomarker produced by renal and non-renal tissues, might be affected by sepsis. We evaluated sNGAL in zero glomerular filtration rate models [bilateral ureter obstruction (BUO) and bilateral nephrectomy (BiNx)] with subsequent cecal ligation and puncture (CLP)-induced sepsis in 6 to 8-week-old ICR mice. We found that sNGAL increased earlier than serum creatinine (Scr) in BiNx/BUO with and without CLP. The earliest time-point of increased sNGAL in BiNx+CLP was 1 h after surgery. Scr, but not sNGAL, was lower at 18 h after BiNx/BUO+CLP compared with BiNx/BUO alone. Compared with BUO, BiNx had higher, and equal sNGAL at 1 to 18 h and 36 h, respectively. Additionally, similar NGAL expression in internal organs (heart, lung, liver, and spleen) and survival rates indicated the comparable severity of BiNx and BUO. Serum interleukin (IL)-6 was increased and correlated with sNGAL in BiNx/BUO with and without sepsis. In summary, we demonstrated: sNGAL is an early AKI biomarker, which is not affected by sepsis; sNGAL is mainly produced by extrarenal sources as demonstrated by the comparable sNGAL in BiNx and BUO; the saturation of renal NGAL re-absorption in BUO is demonstrated by lower sNGAL in BUO at 1 to 18 h, but not at 36 h when compared with BiNx; and a correlation of sNGAL and IL-6 implied sNGAL is a good sepsis prognostic biomarker. Therefore, sNGAL is a more beneficial sepsis-AKI biomarker than Scr. PMID:26863120

  5. Cytokine profile of a Holstein calf with bovine leukocyte adhesion deficiency during the acute-phase inflammatory response.

    PubMed

    Nagahata, Hajime; Hagiwara, Katsuro; Kasamatsu, Masahiko; Higuchi, Hidetoshi; Kurosawa, Takashi

    2002-12-01

    Changes in interleukin (IL)-1beta, IL-6 and IL-8 in serum, and their mRNA expression on neutrophils from a 4.6-month old Holstein young calf with bovine leukocyte adhesion deficiency (BLAD) during the acute phase were evaluated. IL-1beta concentrations in the serum of the calf with BLAD at age 143-162 days ranged from 8.7 to 16.6 ng/ml, whereas the values were less than 2.7 ng/ml in control calves. Serum IL-6 (0.04 ng/ml) was only detected on the 1st day when the animal was diagnosed with the BLAD. IL-1beta and IL-8 mRNA expression on neutrophils from the affected calf appeared to be similar to those of controls. Serum cytokine levels and their mRNA expression on neutrophils from the calf with BLAD appeared to be little affected by the deficient expression of beta(2)-integrin on leukocytes, and are considered to be modulated by the inflammatory stimuli. PMID:12520109

  6. Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves.

    PubMed

    Nonnecke, B J; McGill, J L; Ridpath, J F; Sacco, R E; Lippolis, J D; Reinhardt, T A

    2014-09-01

    Studies in young animals have shown an association between vitamin deficiencies and increased risk of infectious disease; however, there is a paucity of information regarding the effect of acute infection on the vitamin status of the vitamin-replete neonate. To characterize the effects of acute infection on vitamin D and E status of the neonate, 6 vitamin-replete preruminant Holstein bull calves were experimentally infected with bovine viral diarrhea virus (BVDV; strain BVDV2-1373). Six mock-inoculated calves served as controls. Sustained pyrexia, leukopenia, and asynchronous increases in serum haptoglobin and serum amyloid A characterized the response of calves to infection with BVDV. Infection was also associated with increased serum IFN-γ, IL-2, and IL-6 concentrations. During the last 8 d of the 14-d postinoculation period, serum 25-hydroxyvitamin D and α-tocopherol concentrations in infected calves decreased by 51 and 82%, respectively. The observed inverse association between vitamin D and E status and serum amyloid A in infected calves suggests that the infection-induced acute phase response contributed to the reduced vitamin status of these animals. Additional studies are necessary to determine if the negative effect of infection on status are unique to this specific infection model or is representative of preruminant calf's response to acute infection. Studies are also needed to characterize mechanisms underlying infection-related changes in vitamin D and E status and to determine whether additional vitamin D or E supplementation during an acute infection diminishes disease severity and duration in the young animal. PMID:25022687

  7. Effect of digoxin on serum and urinary cation changes on acute induction to high altitude

    SciTech Connect

    Ohri, V.C.; Chatterji, J.C.; Sachdev, Y.R.; Das, B.K.; Akhtar, M.; Tiwari, S.C.; Bhattacharji, P.; Behl, A.; Dutta, S.K.

    1984-04-01

    Forty subjects each were rapidly inducted by road to altitudes of 3200 and 3771 meters (m). Half of subjects at each altitude were maintained on digoxin and the other half received placebos. The digoxin group showed higher serum potassium at both altitudes. Serum sodium remained unaltered. When compared to control groups, urinary volume changes were less marked in the digoxin group. Similarly, the alterations in calcium and magnesium in serum and urine at 3771 m were less pronounced. However, none of these changes in the digoxin groups were statistically significant when compared with control groups. 21 references.

  8. Absence of a serum melatonin rhythm under acutely extended darkness in the horse

    PubMed Central

    2011-01-01

    Background In contrast to studies showing gradual adaptation of melatonin (MT) rhythms to an advanced photoperiod in humans and rodents, we previously demonstrated that equine MT rhythms complete a 6-h light/dark (LD) phase advance on the first post-shift day. This suggested the possibility that melatonin secretion in the horse may be more strongly light-driven as opposed to endogenously rhythmic and light entrained. The present study investigates whether equine melatonin is endogenously rhythmic in extended darkness (DD). Methods Six healthy, young mares were maintained in a lightproof barn under an LD cycle that mimicked the ambient natural photoperiod outside. Blood samples were collected at 2-h intervals for 48 consecutive h: 24-h in LD, followed by 24-h in extended dark (DD). Serum was harvested and stored at -20°C until melatonin and cortisol were measured by commercial RIA kits. Results Two-way repeated measures ANOVA (n = 6/time point) revealed a significant circadian time (CT) x lighting condition interaction (p < .0001) for melatonin with levels non-rhythmic and consistently high during DD (CT 0-24). In contrast, cortisol displayed significant clock-time variation throughout LD and DD (p = .0009) with no CT x light treatment interaction (p = .4018). Cosinor analysis confirmed a significant 24-h temporal variation for melatonin in LD (p = .0002) that was absent in DD (p = .51), while there was an apparent circadian component in cortisol, which approached significance in LD (p = .076), and was highly significant in DD (p = .0059). Conclusions The present finding of no 24 h oscillation in melatonin in DD is the first evidence indicating that melatonin is not gated by a self-sustained circadian process in the horse. Melatonin is therefore not a suitable marker of circadian phase in this species. In conjunction with recent similar findings in reindeer, it appears that biosynthesis of melatonin in the pineal glands of some ungulates is strongly driven by the

  9. Particle-Induced Pulmonary Acute Phase Response Correlates with Neutrophil Influx Linking Inhaled Particles and Cardiovascular Risk

    PubMed Central

    Saber, Anne Thoustrup; Lamson, Jacob Stuart; Jacobsen, Nicklas Raun; Ravn-Haren, Gitte; Hougaard, Karin Sørig; Nyendi, Allen Njimeri; Wahlberg, Pia; Madsen, Anne Mette; Jackson, Petra; Wallin, Håkan; Vogel, Ulla

    2013-01-01

    Background Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk. Methods We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes. Results Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points. Conclusions Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease. PMID:23894396

  10. Use of corticosteroids during acute phase of Kawasaki disease.

    PubMed

    Yu, Jeong Jin

    2015-11-01

    In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary. PMID:26566486

  11. Use of corticosteroids during acute phase of Kawasaki disease

    PubMed Central

    Yu, Jeong Jin

    2015-01-01

    In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary. PMID:26566486

  12. THE ACUTE PHASE RESPONSE IN E. COLI CHALLENGED PIGS TREATED WITH SYSTEMIC ANTIBIOTICS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Changes in serum C-reactive protein (CRP), haptoglobin (HG) and cortisol (CS), and rectal temperature (RT) were evaluated in response to an acute enterotoxemia elicited by antibiotic injection. Twenty-four, 24-day old, pigs were individually housed and provided feed and water ad libitum. Twelve pig...

  13. Smoking is associated with reduced serum paraoxonase, antioxidants and increased oxidative stress in normolipidaemic acute myocardial infarct patients

    PubMed Central

    Kumar, Arun; Biswas, Utpal Kumar

    2011-01-01

    Background Paraoxonase is a high-density lipoprotein (HDL)-associated enzyme that protects lipoproteins from oxidative modifications and from becoming atherogenic in nature. Smoking is a well-known major cardiovascular risk factor that promotes lipid peroxidation (LP). The present study examined the hypothesis that smoking modulates the activity of paraoxonase and depletes antioxidants. Aim The present study evaluated paraoxonase activity, antioxidant status and LP in smoking and non-smoking normolipidaemic acute myocardial infarct (AMI) patients, and results were compared with controls. Settings and design The serum paraoxonase activities, antioxidants and LP were determined in 86 normolipidaemic patients diagnosed of AMI, and 86 age–sex-matched healthy volunteers served as control. Material and methods Serum paraoxonase activities were measured by enzymatic kit. The glutathione peroxidase, superoxide dismutase and catalase activity was determined by standard methods. Malondialdehyde was measured by the thiobarbituric acid reaction, and conjugated diene levels by the Recknagel and Glende method. Serum uric acid, total bilirubin, serum albumin and lipid profiles were analysed by standard methods. Statistics The values were expressed as mean±SD, and data from the patients and control were compared using the Student t test. Results and conclusion The total cholesterol/HDL cholesterol ratio, triglycerides, low-density lipoprotein cholesterol, low-density lipoprotein/HDL cholesterol ratio and triglyceride/HDL cholesterol ratio were significantly higher, and HDL cholesterol significantly lower in smokers compared with non-smoking AMI patients. Superoxide dismutase, glutathione peroxidase and catalase were significantly higher in non-smokers compared with smokers. Serum albumin, uric acid and bilirubin were higher in the control compared with smoking AMI patients. The malondialdehyde and conjugated dienes were significantly higher, and paraoxonase activities were

  14. Association between Serum Bilirubin and Acute Intraoperative Hyperglycemia Induced by Prolonged Intermittent Hepatic Inflow Occlusion in Living Liver Donors

    PubMed Central

    Han, Sangbin; Jin, Sang-Man; Ko, Justin Sangwook; Kim, Young Ri; Gwak, Mi Sook; Son, Hee Jeong; Joh, Jae-Won; Kim, Gaab Soo

    2016-01-01

    Background Intermittent hepatic inflow occlusion (IHIO) is associated with acute hyperglycemia during living donor hepatectomy when the ischemia is prolonged. Bilirubin is a potent antioxidant to play an important role for maintaining insulin sensitivity and preventing hyperglycemia. Thus, we aimed to test whether serum bilirubin level is associated with prolonged IHIO-induced intraoperative hyperglycemia. Methods Seventy-five living liver donors who underwent a prolonged IHIO with a >30 minute cumulative ischemia were included. The association between preoperative serum bilirubin concentrations and the risk of intraoperative hyperglycemia (blood glucose concentration >180 mg/dl) was analyzed using binary logistic regression with adjusting for potential confounders including age and steatosis. Results The number of donors who underwent 3, 4, 5, and 6 rounds of IHIO was 41, 22, 7, and 5, respectively. Twenty-nine (35%) donors developed intraoperative hyperglycemia. Total bilirubin concentration was inversely associated with hyperglycemia risk (odds ratio [OR] 0.033, 95% confidence interval [CI] 0.004–0.313, P = 0.003). There was an interaction between age and total bilirubin concentration: the effect of lower serum total bilirubin (≤0.7 mg/dl) on the development of hyperglycemia was greater in older donors (>40 years) than in younger donors (P = 0.0.028 versus P = 0.212). Both conjugated bilirubin (OR 0.001 95% CI 0.001–0.684) and unconjugated bilirubin (OR 0.011 95% CI 0.001–0.246) showed an independent association with hyperglycemia risk. Conclusions Lower preoperative serum bilirubin was associated with greater risk of prolonged IHIO-induced hyperglycemia during living donor hepatectomy particularly in older donors. Thus, more meticulous glycemic management is recommended when prolonged IHIO is necessary for surgical purposes in old living donors with lower serum bilirubin levels. PMID:27367602

  15. ITIH4 (Inter-Alpha-Trypsin Inhibitor Heavy Chain 4) Is a New Acute-Phase Protein Isolated from Cattle during Experimental Infection

    PubMed Central

    Piñeiro, M.; Andrés, M.; Iturralde, M.; Carmona, S.; Hirvonen, J.; Pyörälä, S.; Heegaard, P. M. H.; Tjørnehøj, K.; Lampreave, F.; Piñeiro, A.; Alava, M. A.

    2004-01-01

    We have isolated from calf serum a protein with an apparent Mr of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4, the heavy chain 4 of the inter-alpha-trypsin inhibitor family. The response of this protein in the sera was determined for animals during experimental bacterial and viral infections. In the bacterial model, animals were inoculated with a mixture of Actinomyces pyogenes, Fusobacterium necrophorum, and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease. Animals with experimental infections with bovine respiratory syncytial virus (BRSV) also showed increases in ITIH4 concentration (from two- to fivefold), which peaked at around 7 to 8 days after inoculation. Generally, no response was seen after a second infection of the same animals with the virus. Because of the significant induction of the protein in the animals in the mastitis and BRSV infection models, we can conclude that ITIH4 is a new positive acute-phase protein in cattle. PMID:15213118

  16. Insulinlike Growth Factor I Plus Insulinlike Growth Factor Binding Protein 3 Attenuates the Proinflammatory Acute Phase Response in Severely Burned Children

    PubMed Central

    Jeschke, Marc G.; Barrow, Robert E.; Herndon, David N.

    2000-01-01

    Objective To determine the effect of insulinlike growth factor I (IGF-I) in combination with its principal binding protein (IGFBP-3) on the hepatic acute phase response in severely burned children. Summary Background Data The hepatic acute phase response is a cascade of events initiated to restore homeostasis after trauma. A prolonged response, however, may contribute to multiple organ failure, hypermetabolism, complications, and death. Methods Twenty-two children with a mean total body surface area (TBSA) burn of 57 ± 3% were given a continuous infusion of 1 to 4 mg/kg/day IGF-I/BP-3 for 5 days after wound excision and grafting. Eight children with a TBSA burn of 54 ± 4% were given saline as controls. Before and 5 days after excision and grafting, blood samples were taken for serum hepatic constitutive protein, acute phase protein, and proinflammatory cytokine analysis. Results Serum IGF-I levels in burned children given the IGF-I/BP-3 complex increased from 113 ± 15 to 458 ± 40 ng/mL and IGFBP-3 levels increased from 1.8 ± 0.2 to 3.1 ± 0.3 ng/mL. Levels of serum constitutive hepatic proteins (prealbumin, retinol-binding protein, and transferrin) increased with IGF-I/BP-3, whereas levels of type I acute phase proteins (C-reactive protein, α1-acid glycoprotein, and complement C-3) decreased when compared with controls. The complex had no effect on type II acute phase proteins. Tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels decreased with IGF-I/BP-3 compared with controls, with no effect on interleukin-6. Conclusion Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1β and TNF-α followed by a decrease in type I acute phase proteins that was associated with a concomitant increase in constitutive hepatic proteins. Attenuating the proinflammatory acute phase with IGF-1/BP-3 response may prevent multiple organ failure and improve clinical outcomes after thermal injury without any detectable adverse side effects. PMID

  17. Acute-phase responses in cattle infected with hydatid cysts and microbial agents.

    PubMed

    Sevimli, A; Sevimli, F K; Şeker, E; Ulucan, A; Demirel, H H

    2015-07-01

    The aim of this study was to investigate the effect of hydatid cysts and microbial agents on the acute-phase response in cattle. Twenty-seven cattle with hydatid cysts and eight apparently healthy cattle comprised the study and control groups, respectively. Parasitological, microbiological, histopathological and immunohistochemical examinations of the liver and lungs were undertaken, and 49 of these organs were infected with cysts. In 14 of 31 (45.1%) livers and 10 of 18 (55.5%) lungs microbial growth was observed. The most frequent species occurring in the liver were Staphylococcus aureus, Escherichia coli, Corynebacterium spp. and Campylobacter spp., whereas in the lungs the most common species was Candida spp., followed by Streptococcus spp., Mannheimia haemolytica, Corynebacterium spp., Micrococcus spp. and S. aureus. The concentration of serum interleukin (IL-6) in infected cattle, 455.35 ± 39.68 pg/ml, was significantly higher than that of 83.02 ± 17.87 pg/ml in the control group (P0.05). The highest concentrations of IL-6 were detected in serum of the cattle where microbial growth had been detected, followed by cattle infected with bacteria + Trichostrongylus sp. (P< 0.001). Consequently, SAA showed an important increase in the group infected with hydatid cysts, whereas haptoglobin level decreased. It was noticed that IL-6, like SAA, had a significant role in hydatid cyst infection. Therefore IL-6 and SAA appear to be major markers in the detection of infection of cattle with hydatid cysts. PMID:26017333

  18. Incidence and Risk Factors of Acute Kidney Injury after Radical Cystectomy: Importance of Preoperative Serum Uric Acid Level

    PubMed Central

    Joung, Kyoung-Woon; Choi, Seong-Soo; Kong, Yu-Gyeong; Yu, Jihion; Lim, Jinwook; Hwang, Jai-Hyun; Kim, Young-Kug

    2015-01-01

    Background: Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. While radical cystectomy associates significantly with an increased risk of serious complications, including AKI, risk factors of AKI after radical cystectomy has not been reported. This study was performed to determine the incidence and independent predictors of AKI after radical cystectomy. Methods: All consecutive patients who underwent radical cystectomy in 2001-2013 in a single tertiary-care center were identified. Their demographics, laboratory values, and intraoperative data were recorded. Postoperative AKI was defined and staged according to the Acute Kidney Injury Network criteria on the basis of postoperative changes in creatinine levels. Independent predictors of AKI were identified by univariate and multivariate logistic regression analyses. Results: Of the 238 patients who met the eligibility criteria, 91 (38.2%) developed AKI. Univariate logistic regression analyses showed that male gender, high serum uric acid level, and long operation time associated with the development of AKI. On multivariate logistic regression analysis, preoperative serum uric acid concentration (odds ratio [OR] = 1.251; 95% confidence interval [CI] = 1.048-1.493; P = 0.013) and operation time (OR = 1.005; 95% CI = 1.002-1.008; P = 0.003) remained as independent predictors of AKI after radical cystectomy. Conclusions: AKI after radical cystectomy was a relatively common complication. Its independent risk factors were high preoperative serum uric acid concentration and long operation time. These observations can help to prevent AKI after radical cystectomy. PMID:26283877

  19. Serum leptin and cortisol, related to acutely perceived academic examination stress and performance in female university students.

    PubMed

    Haleem, Darakhshan J; Inam, Qurrat-Ul-Aen; Haider, Saida; Perveen, Tahira; Haleem, Muhammad Abdul

    2015-12-01

    Leptin, identified as an antiobesity hormone, also has important role in responses to stress and processing of memory. This study was designed to determine effects of academic examination stress-induced changes in serum leptin and its impact on academic performance. Eighty five healthy female students (age 19-21 years; BMI 21.9 ± 1.6) were recruited for the study. Serum leptin and cortisol were monitored at base line (beginning of academic session) and on the day of examination; using a standardized ELISA kit. Acute perception of academic examination stress was determined with the help of a questionnaire derived from Hamilton Anxiety Scale and self report of stress perception. Academic performance was evaluated by the percentage of marks obtained in the examination. Serum cortisol levels were positively correlated (p < 0.01) with the subjective perception of examination stress but not with academic performance. There was an inverted U-shape relationship between level of stress and academic performance. Leptin increased in all stress groups and correlated (p < 0.01) positively with academic performance. There was an inverted U-shape relationship between level of stress and circulating leptin. The findings suggest the peptide hormone, leptin, is a biomarker of stress perception and a mediator of facilitating effects of stress on cognition. PMID:26187200

  20. CCI-779 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, or Chronic Myelogenous Leukemia in Blastic Phase

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

  1. Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia

    SciTech Connect

    Taylor, G.J.; Crampton, R.S.; Gibson, R.S.; Stebbins, P.T.; Waldman, M.T.; Beller, G.A.

    1981-07-01

    The prospectively assessed time course of changes in ventricular repolarization during acute myocardial infarction (AMI) is reported in 32 patients admitted 2.0 +/- 1.8 (SD) hours after AMI onset. The initial corrected QT interval (QTc) upon hospitalization was longer in the 14 patients developing ventricular tachycardia (VT) within the first 48 hours as compared to QTc in the eight patients with frequent ventricular premature beats (VPBs) and to QTc in the 10 patients with infrequent VPBs. By the fifth day after AMI onset, the QTc shortened significantly only in the VT group, suggesting a greater initial abnormality of repolarization in these patients. All 32 patients had coronary angiography, radionuclide ventriculography, and myocardial perfusion scintigraphy before hospital discharge. Significant discriminating factors related to early phase VT in AMI included initially longer QT and QTc intervals, faster heart rate, higher peak serum levels of creatine kinase, acute anterior infarction, angiographically documented proximal stenosis of the left anterior descending coronary artery, and scintigraphic evidence of hypoperfusion of the interventricular septum. Prior infarction, angina pectoris, hypertension, multivessel coronary artery disease, and depressed left ventricular ejection fraction did not provide discrimination among the three different ventricular arrhythmia AMI groups. Researchers conclude that (1) the QT interval is frequently prolonged early in AMI, (2) the initial transiently prolonged ventricular repolarization facilitates and predicts complex ventricular tachyarrhythmias within the first 48 hours of AMI, (3) jeopardized blood supply to the interventricular septum frequently coexists, and (4) therapeutic enhancement of rapid recovery of the ventricular repolarization process merits investigation for prevention of VT in AMI.

  2. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    NASA Astrophysics Data System (ADS)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  3. Induction of acute phase gene expression by brain irradiation

    SciTech Connect

    Hong, Ji-Hong |; Sun, Ji-Rong; Withers, H.R.

    1995-10-15

    To investigate the in vivo acute phase molecular response of the brain to ionizing radiation, C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1{alpha}, IL-1{beta}, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-{gamma}), tumor necrosis factors (TNF-{alpha} and TNF-{beta}), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), {alpha}1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. Levels of TNF-{alpha}, IL-1{beta}, ICAM-1, EB22/5.3, and to a lesser extent IL-1{alpha} and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances. 64 refs., 4 figs.

  4. Comparative evaluation of immunoglobulin M neutralizing antibody response in acute-phase sera and virus isolation for the routine diagnosis of enterovirus infection.

    PubMed Central

    Pozzetto, B; Gaudin, O G; Aouni, M; Ros, A

    1989-01-01

    A total of 314 patients exhibiting symptoms consistent with a viral disease provided, during the early stage of hospitalization, at least one specimen from a peripheral site (throat or stools or both) and a serum specimen in order to evaluate the neutralizing immunoglobulin M (IgM) antibody response in acute-phase serum in comparison with virus isolation for the rapid diagnosis of enterovirus (EV) infection. IgM antibodies were fractionated by ion-exchange chromatography and tested by seroneutralization against the various types of EV that have been recently circulating. A total of 189 patients (60%) were negative, and 21 (7%) were positive by both methods; in 51 patients (16%), a virus was isolated without IgM antibody response; 53 patients (17%) showed the opposite pattern. In all age groups except for children under 6 months, the frequency of positive results was higher with IgM serology than with virus isolation (27 and 22%, respectively). Apart from meningitis, for which isolation was more efficient, the other clinical conditions were associated with similar percentages of positivity by both methods. Regarding the 21 cases with positive results by the two techniques, the same serotype was detected in 9 cases and different serotypes were detected in 12, suggesting crossreactivities. Thus, IgM neutralizing antibody response on acute-phase serum appears to be of limited value in the rapid diagnosis of acute EV infection but may prove useful for the investigation of the wide range of chronic diseases associated with EV. PMID:2542363

  5. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-01-01

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms. PMID:27323085

  6. Intestinal pathogens, diarrhoea and acute phase proteins in naturally infected dairy calves.

    PubMed

    Seppä-Lassila, Leena; Orro, Toomas; Lassen, Brian; Lasonen, Riikka; Autio, Tiina; Pelkonen, Sinikka; Soveri, Timo

    2015-08-01

    In this study, the association between Eimeria spp. related signs and innate immune response in dairy calves was examined. Calves (n=100) aged 15-60 days were clinically examined and faecal samples, blood samples and deep nasopharyngeal swabs obtained. The samples were analysed for intestinal pathogens, acute phase proteins and WBC count, and respiratory tract pathogens, respectively. Diarrhoea was diagnosed in 32.6% (23.3-43.0%, 95% CI) of calves. An association between the pathogenic Eimeria spp. and diarrhoea was detected by multiple correspondence analysis. Eimeria related signs (diarrhoea, presence of pathogenic species and total oocyst count) were combined resulting a four level variable. Calves with weak signs of eimeriosis had decreased haptoglobin concentrations (p=0.02) and increased fibrinogen concentrations (p=0.048) compared to no signs. Increased haptoglobin and fibrinogen concentrations were associated with respiratory tract infection and umbilical infection. Serum amyloid A and WBC counts showed no association with signs of eimeriosis or clinical diagnoses. PMID:26264522

  7. The effect of transport stress on turkey (Meleagris gallopavo) liver acute phase proteins gene expression.

    PubMed

    Marques, Andreia Tomás; Lecchi, Cristina; Grilli, Guido; Giudice, Chiara; Nodari, Sara Rota; Vinco, Leonardo J; Ceciliani, Fabrizio

    2016-02-01

    The aim of this study was to investigate the effects of transport-related stress on the liver gene expression of four acute phase proteins (APP), namely α1-acid glycoprotein (AGP), C-Reactive Protein (CRP), Serum Amyloid A (SAA) and PIT54, in turkeys (Meleagris gallopavo). A group of seven BUT BIG 6 commercial hens was subjected to a two-hour long road transportation and the quantitative gene expression of APP in the liver was compared to that of a non transported control group. The expression of AGP and CRP mRNA was found to be increased in animals slaughtered after road transport. The presence of AGP protein was also confirmed by immunohistochemistry and Western blotting. The results of this study showed that road-transport may induce the mRNA expression of immune related proteins. The finding that AGP and CRP can be upregulated during transport could suggest their use as for the assessment of turkey welfare during transport. PMID:26850544

  8. Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis

    PubMed Central

    Christianson, Christina A.; Corr, Maripat; Firestein, Gary S.; Mobargha, Anahita; Yaksh, Tony L.; Svensson, Camilla I.

    2010-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that affects approximately 1% of the population. Synovial inflammation cannot fully explain the level of pain reported by patients and facilitation of pain processing at the spinal level has been implicated. We characterized the K/BxN serum transfer arthritis model as a model of joint inflammation-induced pain and examine pharmacologic responsiveness and spinal glia activation. Mechanical allodynia developed congruently with joint swelling. Surprisingly, allodynia persisted after resolution of inflammation. At the peak of joint inflammation, (days 4–10) hypersensitivity was attenuated with i.p. etanercept, gabapentin, and ketorolac. Following resolution of synovial inflammation (day 19–28), only gabapentin relieved allodynia. The superficial dorsal horn of arthritic mice displayed increased staining of microglia at early and late time points, but astrocyte staining increased only during the inflammatory phase. ATF3, a marker of nerve injury, was significantly increased in the lumbar dorsal root ganglia during the late phase (day 28). Hence, serum transfer in the K/BxN serum transfer arthritis model produces a persistent pain state, where the allodynia during the inflammatory state is attenuated by TNF and prostaglandin inhibitors, and the pharmacology and histochemistry data suggest a transition from an inflammatory state to a state that resembles a neuropathic condition over time. Therefore, the K/BxN serum transfer model represents a multifaceted model for studies exploring pain mechanisms in conditions of joint inflammation and may serve as a platform for exploring novel treatment strategies for pain in human arthritic conditions. K/BxN serum transfer arthritis produces persistent mechanical hypersensitivity despite resolution of clinical signs with evidence of transition from an inflammatory to neuropathic pain state. PMID:20739123

  9. Systemic acute phase proteins response in calves experimentally infected with Eimeria zuernii.

    PubMed

    Lassen, Brian; Bangoura, Berit; Lepik, Triin; Orro, Toomas

    2015-09-15

    Acute phase proteins (APPs) have been demonstrated to be useful in evaluating general health stress and diseases in cattle. Serum amyloid A (SAA) and haptoglobin (Hp) are APPs that are produced during inflammation, and likely play a role in host immunological defence against Eimeria infection and the associated intestinal tissue damage. We investigated the involvement of SAA and HP in an experimental study, including three groups of calves: a control group (group 0, n=11), and two groups infected with either 150,000 or 250,000 Eimeria zuernii oocysts (group 1 (n=11) and group 2 (n=12), respectively). The calves were monitored for 28 days and data was collected on oocyst excretion, faecal score, animal weight, and SAA and Hp serum concentrations. Generalized linear mixed models showed that the clinical symptoms, indicated by an increase in the number of oocysts in the faeces and severe diarrhoea, manifested at patency for group 1 and 2. Serum Hp and SAA levels also increased during this period. Hp appeared to be a more sensitive marker than SAA, and differences between groups 1 and 2 were observed only for Hp. Linear regression models showed a negative association between weight gain and Hp concentrations, calculated as the area under the curve (AUC) during the overall experimental period and the patency period. A similar result was seen for SAA only during the patency period. This result supports the assumption that reduced weight gain due to E. zuernii infection is an immunologically driven process that involves an increase in APPs. A random intercept regression model of oocyst shedding groups showed that calves shedding 1-500 oocysts had reduced concentrations of Hp, indicating that a different immunological reaction occurs during mild shedding of E. zuernii oocysts than during more intensive shedding. A similar model was used to examine associations between faecal scores and Hp concentrations for each group. Group 2 calves with haemorrhagic diarrhoea displayed

  10. Evaluation of Serum Pregnancy Associated Plasma Protein-A & Plasma D-Dimer in Acute Coronary Syndrome

    PubMed Central

    Thomas, Vivian Samuel

    2016-01-01

    Introduction Acute coronary syndrome (ACS), a spectrum comprising unstable angina pectoris, ST Elevated Myocardial Infarction (STEMI) & Non ST Elevated Myocardial Infarction (NSTEMI) is the major cause of presentation in Emergency Department today. Though ECG and cardiac enzymes are used for diagnosis, they mislead the diagnosis sometimes and delay in treatment initiation. This leads us to search certain new parameters which reflect the pathophysiology of ACS. Markers of plaque stability like Pregnancy Associated Plasma Protein-A and D-Dimer, a marker of ongoing thrombosis are found to be better markers in early diagnosis. Aim To evaluate the diagnostic competence of PAPP-A and D-Dimer in acute coronary syndrome over CK-MB and to compare with the inflammatory marker High Sensitive C-Reactive Protein (hs-CRP) which is associated with atherosclerosis. Materials and Methods Fifty patients presenting with acute onset of chest pain to Emergency Department with or without ECG changes served as cases and 50 healthy people served as controls. Serum PAPP-A is measured by Enzyme Linked Immunosorbent Assay (ELISA), D-Dimer and hs-CRP by using Latex Turbidimetry method. Results A statistical significant difference of PAPP-A and D-Dimer was noted between the ACS and controls (p < 0.001) whereas CK-MB shows no much difference (p 0.09). Statistically significant positive correlation is noted between parameters. Conclusion PAPP-A marker of plaque instability and D-Dimer marker of ongoing thrombosis are raised in acute coronary syndrome and thus can be considered as one of the marker in ACS for diagnosis. PMID:26894054

  11. Acute phase proteins increase with sarcoptic mange status and severity in Iberian ibex (Capra pyrenaica, Schinz 1838).

    PubMed

    Ráez-Bravo, Arián; Granados, José Enrique; Cerón, José Joaquín; Cano-Manuel, Francisco Javier; Fandos, Paulino; Pérez, Jesús María; Espinosa, José; Soriguer, Ramón Casimiro; López-Olvera, Jorge Ramón

    2015-11-01

    Sarcoptic mange is a contagious skin disease caused by Sarcoptes scabiei, affecting both domestic and wild mammals, including the Iberian ibex (Capra pyrenaica), a medium-sized mountain ungulate almost endemic to the Iberian Peninsula. Acute phase proteins (APPs) could be an indicator of sarcoptic mange disease and severity in Iberian ibex. Serum samples from 131 healthy and sarcoptic mange-affected Iberian ibexes were collected from 2005 to 2012 in Sierra Nevada Natural Space in southern Spain. Serum alpha-1-acid glycoprotein (AGP), serum amyloid A (SAA) and haptoglobin (Hp) concentrations were quantified, and statistically significant differences according to sarcoptic mange disease and severity were assessed. Both AGP and SAA were significantly higher in the sarcoptic mange-affected ibexes than in the healthy ones as well as in the severely affected ibexes as compared to those with less than 50 % of the body surface affected. For the first time, changes in APP are reported in relation to sarcoptic mange in Iberian ibex. It is also reported for the first time that the intensity of APP increase depends on the severity of sarcoptic mange, which could be related with the pathological secondary amyloidosis, leading to organ dysfunction in severely mange-affected animals. Species and population differences in the increase of APP in response to sarcoptic mange could indicate individual and population differences in the immune capability of each population to deal with mange, population prevalence and mortality being the last indicators of such sensitivity. PMID:26227139

  12. [Effect of shengmaisan on serum lipid peroxidation in acute viral myocarditis].

    PubMed

    Zhao, M H; Rong, Y Z; Lu, B J

    1996-03-01

    The effect of Shengmaisan (SMS) on 62 acute viral myocarditis patients and its peroxidation damage was studied. The results revealed that the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in blood were decreased and the content of malondialdehyde (MDA) in plasma was increased in acute viral myocarditis patients in comparison with the healthy controls (P < 0.001). 62 acute viral myocarditis patients were divided into two groups: SMS group and placebo group. After treatment, both SOD and GSH-Px activities were increased and the level of MDA decreased (P < 0.001) in SMS group, while those in placebo group were not changed (P < 0.05). The results suggested that the myocardial damage of viral myocarditis is closely related with lipid peroxidation SMS acts as an effective free radical scavenger and anti-lipid peroxidation drug. SMS could prevent the damage of myocardia and might be taken as one of the effective therapeutic methods in treatment of acute viral myocarditis. PMID:9208534

  13. Predictors of Longitudinal Outcomes after Unstable Response to Acute Phase Cognitive Therapy for Major Depressive Disorder

    PubMed Central

    Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.; Jarrett, Robin B.

    2015-01-01

    After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT (C-CT), double-blinded fluoxetine or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT. PMID:25985046

  14. Correlation of serum C-reactive protein, white blood count and neutrophil percentage with histopathology findings in acute appendicitis

    PubMed Central

    2012-01-01

    -value <0.05). CRP monitoring enhances the diagnostic accuracy of acute appendicitis. The diagnostic accuracy of CRP is not significantly greater than WBC and NP. A combination of these three tests significantly increases the accuracy. We found that elevated serum CRP levels support the surgeon's clinical diagnosis. PMID:22866907

  15. Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level.

    PubMed Central

    Wegenka, U M; Buschmann, J; Lütticken, C; Heinrich, P C; Horn, F

    1993-01-01

    Interleukin-6 (IL-6) is known to be a major mediator of the acute-phase response in liver. We show here that IL-6 triggers the rapid activation of a nuclear factor, termed acute-phase response factor (APRF), both in rat liver in vivo and in human hepatoma (HepG2) cells in vitro. APRF bound to IL-6 response elements in the 5'-flanking regions of various acute-phase protein genes (e.g., the alpha 2-macroglobulin, fibrinogen, and alpha 1-acid glycoprotein genes). These elements contain a characteristic hexanucleotide motif, CTGGGA, known to be required for the IL-6 responsiveness of these genes. Analysis of the binding specificity of APRF revealed that it is different from NF-IL6 and NF-kappa B, transcription factors known to be regulated by cytokines and involved in the transcriptional regulation of acute-phase protein genes. In HepG2 cells, activation of APRF was observed within minutes after stimulation with IL-6 or leukemia-inhibitory factor and did not require ongoing protein synthesis. Therefore, a preexisting inactive form of APRF is activated by a posttranslational mechanism. We present evidence that this activation occurs in the cytoplasm and that a phosphorylation is involved. These results lead to the conclusions that APRF is an immediate target of the IL-6 signalling cascade and is likely to play a central role in the transcriptional regulation of many IL-6-induced genes. Images PMID:7678052

  16. Methylprednisolone-hemisuccinate and its metabolites in serum, urine and bile from two patients with acute graft rejection.

    PubMed Central

    Lawson, G J; Chakraborty, J; Tredger, J M; Baylis, E M

    1995-01-01

    Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-alpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (20 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h intravenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patients with rheumatoid arthritis (historical controls) who had normal liver function. The transplant patients showed a ratio in urine of 'total metabolites'/MPHS that was one third that of patients with rheumatoid arthritis. Less than 0.2% of the administered MPHS appeared in bile as MPHS, MP, 20 alpha HMP and 20 beta HMP during the 24 h following infusion. Liver transplantation did not affect the overall elimination of drug in urine. However, the impaired liver function following transplantation resulted in reduced conversion of MPHS to its active form (MP). PMID:7742157

  17. Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response

    PubMed Central

    Kirkconnell, Killeen S.; Paulsen, Michelle T.; Magnuson, Brian; Bedi, Karan

    2016-01-01

    ABSTRACT Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent RNA Bru-seq technique in order to capture early dynamic changes in the nascent transcriptome. Our data provides an unprecedented view of the dynamics of genome-wide transcription during the first two hours of serum stimulation in human fibroblasts. While some genes showed sustained induction or repression, other genes showed transient or delayed responses. Surprisingly, the dynamic patterns of induction and suppression of response genes showed a high degree of similarity, suggesting that these opposite outcomes are triggered by a common set of signals. As expected, early response genes such as those encoding components of the AP-1 transcription factor and those involved in the circadian clock were immediately but transiently induced. Surprisingly, transcription of important DNA damage response genes and histone genes were rapidly repressed. We also show that RNA polymerase II accelerates as it transcribes large genes and this was independent of whether the gene was induced or not. These results provide a unique genome-wide depiction of dynamic patterns of transcription of serum response genes and demonstrate the utility of Bru-seq to comprehensively capture rapid and dynamic changes of the nascent transcriptome. PMID:27230646

  18. Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response.

    PubMed

    Kirkconnell, Killeen S; Paulsen, Michelle T; Magnuson, Brian; Bedi, Karan; Ljungman, Mats

    2016-01-01

    Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent RNA Bru-seq technique in order to capture early dynamic changes in the nascent transcriptome. Our data provides an unprecedented view of the dynamics of genome-wide transcription during the first two hours of serum stimulation in human fibroblasts. While some genes showed sustained induction or repression, other genes showed transient or delayed responses. Surprisingly, the dynamic patterns of induction and suppression of response genes showed a high degree of similarity, suggesting that these opposite outcomes are triggered by a common set of signals. As expected, early response genes such as those encoding components of the AP-1 transcription factor and those involved in the circadian clock were immediately but transiently induced. Surprisingly, transcription of important DNA damage response genes and histone genes were rapidly repressed. We also show that RNA polymerase II accelerates as it transcribes large genes and this was independent of whether the gene was induced or not. These results provide a unique genome-wide depiction of dynamic patterns of transcription of serum response genes and demonstrate the utility of Bru-seq to comprehensively capture rapid and dynamic changes of the nascent transcriptome. PMID:27230646

  19. Acute ingestion of catechin-rich green tea improves postprandial glucose status and increases serum thioredoxin concentrations in postmenopausal women.

    PubMed

    Takahashi, Masaki; Miyashita, Masashi; Suzuki, Katsuhiko; Bae, Seong-Ryu; Kim, Hyeon-Ki; Wakisaka, Takuya; Matsui, Yuji; Takeshita, Masao; Yasunaga, Koichi

    2014-11-14

    Elevated postprandial hyperglycaemia and oxidative stress increase the risks of type 2 diabetes and CVD. Green tea catechin possesses antidiabetic properties and antioxidant capacity. In the present study, we examined the acute and continuous effects of ingestion of catechin-rich green tea on postprandial hyperglycaemia and oxidative stress in healthy postmenopausal women. Participants were randomly assigned into the placebo (P, n 11) or green tea (GT, n 11) group. The GT group consumed a catechin-rich green tea (catechins 615 mg/350 ml) beverage per d for 4 weeks. The P group consumed a placebo (catechins 92 mg/350 ml) beverage per d for 4 weeks. At baseline and after 4 weeks, participants of each group consumed their designated beverages with breakfast and consumed lunch 3 h after breakfast. Venous blood samples were collected in the fasted state (0 h) and at 2, 4 and 6 h after breakfast. Postprandial glucose concentrations were 3 % lower in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). Serum concentrations of the derivatives of reactive oxygen metabolites increased after meals (P< 0·05), but no effect of catechin-rich green tea intake was observed. Conversely, serum postprandial thioredoxin concentrations were 5 % higher in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). These findings indicate that an acute ingestion of catechin-rich green tea has beneficial effects on postprandial glucose and redox homeostasis in postmenopausal women. PMID:25230741

  20. The Evaluation of Serum Copeptin Levels and Some Commonly Seen Thrombophilic Mutation Prevalence in Acute Pulmonary Embolism.

    PubMed

    Ozturk, Nurinnisa; Baygutalp, Nurcan Kilic; Bayramoglu, Atif; Polat, Harun; Gul, Mehmet Ali; Bakan, Ebubekir; Aslan, Sahin; Gunes, Ozge Nur

    2016-06-01

    Acute pulmonary embolism (PE) is a common, emergent condition and may affect a large number of patients. Copeptin has been indicated to be a sensitive biomarker of arginine vasopressin release, and has diagnostic and prognostic value in various clinical conditions. Genetic mutations are considerable components of thrombophilic diseases, and factor II gene G20210A, (FII20210A), factor V Leiden (FVL, G1691A) and methylenetetrahydrofolate reductase gene C677T (MTHFR677T) single nucleotide polymorphisms are the most common mutations of thrombophilic diseases. In this study, serum copeptin levels were determined in patients with PE and healthy controls, and the results were discussed. The prevalence of some commonly seen thrombophilic mutations was also evaluated in patients with PE. The study included 32 patients (18 male, 14 female) with PE and 24 (13 male, 11 female) age- and gender-matched healthy controls. A significant difference in serum copeptin levels was determined between the patient and control groups (8.58 ± 4.42 and 4.07 ± 1.02 pmol/L, respectively). Heterozygous mutant genotype for FII20210A and heterozygous mutant genotype for FVL were observed in 3.1 and 9.4% of patients, respectively. Mutant genotype of 49% was determined for MTHFR677T mutations. It was concluded that copeptin may have diagnostic value for PE. PMID:26886096

  1. Increased serum concentrations of soluble CD95/Fas and caspase 1/ICE in patients with acute angina

    PubMed Central

    Ankersmit, H J; Weber, T; Auer, J; Roth, G; Brunner, M; Kvas, E; Moser, B; Spreitzer, S; Lassnig, E; Maurer, E; Hartl, P; Wolner, E; Boltz-Nitulescu, G; Eber, B

    2004-01-01

    Objectives: To investigate the expression of death inducing receptors in the sera of patients with stable and unstable angina. Design: 80 consecutive patients with stable (n  =  40) or unstable (n  =  40) angina pectoris were studied. Serum concentrations of soluble CD95 (sCD95), soluble CD95 ligand (sCD95L; CD178), tumour necrosis factor (TNF) α, soluble TNFα receptor type 1 (sTNFR1), and interleukin 1β converting enzyme (ICE; caspase 1) were measured by enzyme linked immunosorbent assay (ELISA). Results: Significant increases in the concentrations of sCD95 and ICE (p < 0.001 and p < 0.023, respectively) were found in the serum from patients with unstable angina relative to those with stable angina. There were no significant differences in the concentrations of sCD95L, TNF α, and sTNFR1 between the groups. Conclusions: These data provide the first evidence that sCD95 and ICE are important serological markers that may help to discriminate between stable and unstable angina. This observation may warrant further clinical study to elucidate the clinical impact of sCD95 and ICE in acute coronary syndromes. PMID:14729783

  2. Serum albumin: touchstone or totem?

    PubMed

    Margarson, M P; Soni, N

    1998-08-01

    A decrease in serum albumin concentrations is an almost inevitable finding in disease states, and is primarily mediated in the acute phase by alterations in vascular permeability and redistribution. This change is not disease specific but marked changes that persist are generally associated with a poorer prognosis. Critical appraisal of long-standing practices and the availability of alternative colloid solutions have led to a reduction in albumin replacement therapy, and a widespread tolerance of lower albumin concentrations in patients. The factors determining serum albumin concentrations, their measurement and the implications of hypoalbuminaemia are reviewed. The clinical value of serum albumin measurement is discussed. PMID:9797524

  3. Neutrophil to lymphocyte ratio might help prediction of acute myocardial infarction in patients with elevated serum creatinine

    PubMed Central

    Nalbant, Ahmet; Cinemre, Hakan; Kaya, Tezcan; Varim, Ceyhun; Varim, Perihan; Tamer, Ali

    2016-01-01

    Background and Objective: Diagnostic performance of troponin assays is affected by renal insufficiency. Neutrophil to lymphocyte ratio(NLR) is an independent predictor of acute coronary syndrome. Our objective was to evaluate performance of NLR in diagnosing acute myocardial infarction (AMI) among patients with elevated serum creatinine. Methods: Patients with elevated creatinine levels evaluated for coronary artery disease were included (n=284). Patients were divided into two groups according to having AMI or non-specific chest pain. AMI diagnosis was made based on clinical and laboratory data, including serial EKG and cardiac enzymes, ECHO and coronary angiography. Results: Troponin, neutrophil, and NLR were found to be higher in patients with AMI, compared to patients without AMI (P= 0.001, P= 0.001 and P=0.028, respectively). ROC curve analysis for NLR in diagnosing AMI was significant (AUC: 0.607; P=0.003). Sensitivity, specificity, LR +, LR-, PPV and NPV for NLR>7.4 were found as 42.3%, 74.7%, 1.68%, 0.77%, 77% and 40%, respectively. Logistic regression analysis revealed that patients whose NLR>7.4 were 2.18 times as likely to have AMI. Conclusions: NLR can be used as an independent predictor of AMI in patients with renal insufficiency. This seems to get more important in the era of high sensitivity troponin assays. Our results might also help in early diagnosis of AMI in this high risk population while serial cardiac enzyme results are pending. PMID:27022355

  4. Serum Angiopoietin Levels are Different in Acute and Chronic Myeloid Neoplasms: Angiopoietins do not only Regulate Tumor Angiogenesis.

    PubMed

    Atesoglu, Elif Birtas; Tarkun, Pinar; Mehtap, Ozgur; Demirsoy, Esra Terzi; Atalay, Figen; Maden, Muhammet; Celebi, Koray; Hacihanefioglu, Abdullah

    2016-06-01

    Molecular balance between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) has important effects in tumor angiogenesis. Ang-2 was shown to be elevated and proved to be a prognostic factor in acute myeloid leukemia (AML). To date studies revealed increased angiogenesis in bone marrows (BMs) of both myeloproliferative neoplasm (MPN) and AML patients. We conducted this study to demonstrate circulating levels of Ang-1 and Ang-2 in MPN patients since no data exists in literature. Thirty-three newly diagnosed MPN, 27 newly diagnosed AML patients and 25 controls (HC) were enrolled and Angiopoietin levels were determined with ELISA. We found that Ang-1 levels were higher whereas Ang-2 levels were lower in MPN and HC when compared to AML. Our results suggest that though angiogenesis is increased in both AML and MPN, angiopoietin serum level profile of the two diseases are different, and MPN patients have similar Ang-1 and Ang-2 levels as HC. We conclude that, according to our results Ang-1 and Ang-2 do not only regulate tumor angiogenesis and the difference between angiopoietin levels of acute and chronic myeloid neoplasms could be a reflection of other effects of these growth factors on tumor malignancy. PMID:27065577

  5. THE ACUTE PHASE RESPONSE INDUCED BY BRONCHOSCOPY WITH LAVAGE

    EPA Science Inventory

    Bronchoscopy has been used to evaluate the inflammatory responses in vitro and in vivo. The procedure may affect acute inflammation in the lower respiratory tract. We reviewed consecutive bronchoscopies done in normal healthy non-smokers between April, 1998 and April, 2004. The...

  6. Determination of theophylline in serum by molecularly imprinted solid-phase extraction with pulsed elution.

    PubMed

    Mullett, W M; Lai, E P

    1998-09-01

    The technique of molecular imprinting is used to produce an extensively cross-linked poly(methacrylic acid-co-ethylene dimethacrylate) material that contains theophylline as a print molecule. After Soxhlet extraction of the theophylline, binding sites are formed in the polymer with complementary size, shape, and positioning of chemical functionalities. The molecularly imprinted polymer's (MIP) high theophylline selectivity, chemical stability, and physically robust nature make it an ideal stationary-phase material in columns for HPLC separation of theophylline from other structurally related drug compounds. Mobile-phase tests confirm that a retention mechanism typical of normal-phase chromatography governs the separation, and selectivity of the MIP column can be controlled by a combination of the mobile phase and the sample solvent. Under optimal conditions, the MIP column functions like a solid-phase sorbent for theophylline extraction. Rapid elution of the bound theophylline can be accomplished in a pulsed format through injection of 20 μL of a solvent that has the proper polarity and protic nature to disrupt the electrostatic interactions and hydrogen bonding between theophylline and binding sites. A concentration detection limit of 120 ng/mL is obtained using direct UV absorption detection at 270 nm, which corresponds to a mass detection limit of 2.4 ng. This new technique, molecularly imprinted solid-phase extraction with pulsed elution (MISPE-PE), permits on-line preconcentration of theophylline from a large volume of dilute sample solution. Using a sample volume of 300 μL, a 40 ng/mL standard solution produces a detectable peak signal. Application of MISPE-PE in serum analysis further demonstrates the high capability of the MIP column to selectively isolate theophylline from other matrix components for fast, accurate determination. PMID:21644709

  7. The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels

    PubMed Central

    Buczinski, Sébastien

    2015-01-01

    The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI. PMID:26587339

  8. Acute and long-term effects of radioiodine therapy on serum levels of calcitonin

    SciTech Connect

    Franke, A.; Oeff, K.

    1984-01-01

    The purpose of this study is to establish data on the radiosensitivity of thyroid C cells and medullary carcinoma of the thyroid (MCT) as reflected by the alterations in serum concentrations of calcitonin (Ct) after radioiodine therapy. Serum levels of Ct were measured by radioimmunoassay in 1437 patients subjected to diagnostic and therapeutic procedures for thyroid diseases. The effect of low dose and of high dose radioiodine therapy (RLO, RHI) was studied in 158 patients with hyperthyroidism and in 84 patients with thyroid cancer, respectively. RLO and RHI were followed by significant alterations in the distribution of Ct values. RLO decreased the occurrence of high values. RHI was followed by the absence of high concentrations and a substantial reduction in normal levels. The effect of RLO was confirmed in 47 patients by comparing their individual levels before and 8 weeks after RLO, the means +- SD being 24.3+-8.3 and 12.6+-5.7 pmol/l, respectively (p<0.001). In 30 patients followed up for late onset hypothyroidism who had been treated by RLO 10-25 years ago, the concentrations of Ct were almost normal (mean +- SD 16.6 +- 5.7 pmol/l).

  9. Serum thyroid hormones and tissue 5'-monodeiodinase activity in acutely thyroidectomized newborn lambs

    SciTech Connect

    Polk, D.H.; Wu, S.Y.; Fisher, D.A.

    1986-08-01

    After either total thyroidectomy or sham operation in full-term fetal sheep, fetuses were delivered and serial blood samples were obtained for measurements of thyroxine (T4), triiodothyronine (T3), and catecholamines. Despite comparable serum T4 values, serum T3 values were lower in the thyroidectomized animals. Four hours after birth, the animals were killed with an intravenous overdose of barbiturate. Brain, thyroid, liver, kidney, and brown adipose tissues were dissected and analyzed for thyroxine 5'-monodeiodinase (5'-MDI) activity in vitro. 5'-MDI activity was comparable in all tissues from sham-operated and thyroidectomized lambs. Plasma epinephrine and norepinehprine concentrations, mean arterial pressure, mean pulse, rectal temperature, and arterial blood gas values were similar in the two groups of animals. These data support the hypothesis that the thyroid gland is the major source of T3 for the T3 surge in the immediate newborn period. They also indicate that the neonatal T3 surge has limited immediate metabolic significance in euthyroid newborns.

  10. Solid-phase dispersive extraction method for analysis of benzodiazepine drugs in serum and urine samples.

    PubMed

    Saito, Koichi; Kikuchi, Yuu; Saito, Rieko

    2014-11-01

    A simple yet highly efficient pretreatment method called solid-phase dispersive extraction (SPDE) was developed and used in combination with liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) for the analysis of benzodiazepines (BZPs) in serum and urine samples. By using a custom-made centrifugal filter, SPDE could be performed in a closed system, thereby minimizing exposure to infectious microbes or hazardous chemicals. The limit of detection and the limit of quantification of nine BZPs were 1-10 and 5-50ng/mL, respectively. The average recoveries of BZPs from pooled serum samples spiked at 50 and 500ng/mL were 89.6-105.0% (RSD: 2.1-6.8%) and 93.6-110.4% (RSD: 2.1-4.2%), respectively, and those from urine samples were 88.7-105.5% (RSD: 2.9-6.4%) and 91.5-101.1% (RSD: 3.6-5.5%), respectively. SPDE-LC/TOF-MS has potential application in forensic science and emergency medicine. PMID:25126966

  11. Simultaneous serum desalting and total protein determination by macroporous reversed-phase chromatography.

    PubMed

    Boichenko, Alexander; Govorukhina, Natalia; van der Zee, Ate G J; Bischoff, Rainer

    2013-04-01

    Macroporous reversed-phase (mRP) chromatography was successfully used to develop an accurate and precise method for total protein in serum. The limits of detection (0.83 μg, LOD) and quantification (2.51 μg, LOQ) for the mRP method are comparable with those of the widely used micro BCA protein assay. The mRP method can be used to determine the total protein concentration across a wide dynamic range by detecting chromatographic peaks at 215 nm and 280 nm. The method has the added advantage of desalting and denaturing proteins, leading to more complete digestion by trypsin and to better LC-MS-MS identification in shotgun proteomics experiments. PMID:23388688

  12. Enantioselective separation of chiral arylcarboxylic acids on an immobilized human serum albumin chiral stationary phase.

    PubMed

    Andrisano, V; Booth, T D; Cavrini, V; Wainer, I W

    1997-01-01

    A series of 12 chiral arylcarboxylic acids were chromatographed on an immobilized human serum albumin chiral stationary phase (HSA-CSP). The effects of solute structure on chromatographic retentions and enantioselective separations were examined by linear regression analysis and the construction of quantitative structure-enantioselective retention relationships. Competitive displacement studies were also conducted using R-ibuprofen as the displacing agent. The results indicate that the enantioselective retention of the solutes takes place at the indole-benzodiazepine site (site II) on the HSA molecule and that chiral recognition is affected by the hydrophobicity and steric volume of the solutes. The displacement studies also identified a cooperative allosteric interaction induced by the binding of R-ibuprofen to site II. PMID:9134695

  13. Association of Serum Leptin Level with Obesity in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Zareifar, S; Shorafa, S; Haghpanah, S; Karamizadeh, Z; Adelian, R

    2015-01-01

    Background Obesity is a medical problem in survivors of childhood acute lymphoblastic leukemia. Obesity is associated with many complications, so it is important to investigate the respective etiology. Leptin is a protein synthesized in the fatty tissue and is effective in the control of obesity. Survey of leptin in acute lymphoblastic leukemia (ALL) survivors could be helpful in controlling obesity. Materials and Methods In this prospective study, 53 pediatric patients diagnosed with ALL between 2006 and 2012 from Southern Iran, were enrolled. We examined body mass index (BMI) status and performed laboratory measuring tests including triglyceride, cholesterol, fasting blood sugar, leptin at diagnosis time and then every 6 months and in the last visit. Results Participants consisted of 35 male and 18 female patients. At the time of diagnosis, 5.66% were overweight or obese, whereas at the end of treatment, approximately 13 patients (24.53%) were overweight or obese. The median and interquartile range (IQR) for blood leptin level were significantly higher for obese patients than other patients (885, 1120 vs. 246, 494 pg/ml), (P=0.030). The median and IQR were also significantly higher in females than in males (861, 969 vs. 204, 267 pg/ml), (P=0.006). Conclusion Obesity is a complication of ALL treatment. It is associated with elevated blood leptin level. Hypothalamus leptin resistance in obese patients should be considered. In each visit, clinicians should weight and their patient’s BMI take into account. PMID:26705449

  14. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  15. Change in Psychosocial Functioning and Depressive Symptoms during Acute-Phase Cognitive Therapy for Depression

    PubMed Central

    Dunn, Todd W.; Vittengl, Jeffrey R.; Clark, Lee Anna; Carmody, Thomas; Thase, Michael E.; Jarrett, Robin B.

    2013-01-01

    Background Major Depressive Disorder (MDD) is highly prevalent, is recurrent, and impairs people’s work, relationships, and leisure. Acute-phase treatments improve psychosocial impairment associated with MDD, but how these improvements occur is unclear. In this study, we tested the hypotheses that reductions in depressive symptoms exceed, precede, and predict improvements in psychosocial functioning. Method Patients with recurrent MDD (N = 523; 68% women, 81% Caucasian; M = 42 years old) received acute-phase Cognitive Therapy (CT; Beck, Rush, Shaw & Emery, 1979). We measured functioning and symptom severity with the Social Adjustment Scale—Self-Report (Weissman & Bothwell, 1976), Range of Impaired Functioning Tool (Leon et al., 1999), Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961), Hamilton Rating Scale for Depression (Hamilton, 1960) and Inventory for Depressive Symptomatology—Self-Report (Rush et al., 1996). We tested cross-lagged correlations between functioning and symptoms measured at baseline and the beginning, middle and end of acute phase CT. Results Pre- to post- treatment improvement in psychosocial functioning and depressive symptoms was large and inter-correlated. Depressive symptoms improved more and sooner than did psychosocial functioning. But among four assessments across the course of treatment, improvements in functioning more strongly predicted later improvement in symptoms than vice versa. Conclusions Improvements in psychosocial functioning and depressive symptoms correlate substantially during acute-phase CT, and improvements in functioning may play a role in subsequent symptom reduction during acute-phase CT. PMID:21781377

  16. Early weaning alters the acute-phase reaction to an endotoxin challenge in beef calves.

    PubMed

    Carroll, J A; Arthington, J D; Chase, C C

    2009-12-01

    Previous research indicates that early weaning before shipment can reduce transportation-induced increases in acute-phase proteins (APP) and can increase feedlot performance in beef calves. These data suggest that the combination of weaning and transport stress may compromise the immune system of calves, thus hindering subsequent performance and health. Therefore, our objective was to determine if the innate immune response of early weaned calves (EW; 80 d of age) differed from normal-weaned calves (NW; 250 d of age) in response to an endotoxin challenge. Eighteen Brahman x Angus calves (8 and 10 EW and NW, respectively; 233 +/- 5 kg of BW) were used. Calves were maintained on pasture with supplement and then moved into individual pens for 1 wk of acclimation before the start of the study. Calves were fitted with an indwelling jugular catheter 1 d before LPS challenge (0 h; 1.0 microg/kg of BW, intravenously). Blood samples were collected at 30-min intervals from -2 to 8 h. Serum samples were stored at -80 degrees C until analyzed for cortisol, tumor necrosis factor-alpha (TNF), IL-1 beta, IL-6, interferon-gamma (IFN), ceruloplasmin, and haptoglobin. Whereas LPS increased serum cortisol (P or= 0.15) was observed. A weaning age x time interaction (P

  17. Parameters of immunity acute phase reaction in men in relation to exposure duration to mercury vapours.

    PubMed

    Moszczynski, P; Moszczynski, P; Słowinski, S; Bem, S; Bartus, R

    1991-01-01

    The study was carried out in 89 men aged 21 to 57 years with a history of exposure to mercury vapour from 2 to 26 years during occupational work involving chlorine production by the method of mercury electrolysis. The workers were divided into three groups depending on the duration of occupational exposure: 1) 32 workers with a short history of exposure 2-10 years, 2) 37 workers with medium-long exposure - 11-20 years, and 3) 20 workers with a history of long exposure - 21-26 years. The urinary concentrations of mercury in these individuals was 73 +/- 60 microliters x 1(-1), and in blood this concentration was not exceeding 50 microliters x 1(-1). The control group comprised 40 men aged 17 to 52 years. They had not had any occupational exposure to chemicals, or harmful physical factors. On the basis of clinical, haematological and biochemical studies 89 workers with occupational exposure to mercury vapour were regarded as clinically healthy. None of them had any symptoms and signs of the complete neurasthenic syndrome or organic brain injury. Increased nervous excitability was the complaint of 24 workers, 9 had headaches, sleep disturbances were reported by 5, and a feeling of tiredness and apathy was mentioned by 5 men. EEG recording demonstrated 81 normal tracings, and moderately pathological records in 8 men. The parameters of immunity and proteins acute phase reaction were determined, measuring the concentration of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, haptoglobin and ceruloplasmin in serum. A lower level of IgA, IgG and lysozyme was only noted in individuals with occupational exposure exceeding 20 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1725175

  18. Changing Patterns of Acute Phase Proteins and Inflammatory Mediators in Experimental Caprine Coccidiosis

    PubMed Central

    Khodakaram-Tafti, Azizollah; Razavi, Seyed Mostafa; Nazifi, Saeed

    2011-01-01

    This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×103 and1×105 sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis. PMID:22072820

  19. Markers of iron status are associated with stage of pregnancy and acute-phase response, but not with parity among pregnant women in Guinea-Bissau.

    PubMed

    Kæstel, Pernille; Aaby, Peter; Ritz, Christian; Friis, Henrik

    2015-10-14

    While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and α1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27% lower during weeks 16-20 of gestation up to 59% lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52% of the women had sTfR levels >2·3 mg/l, while only 25% had serum ferritin levels 2·3 mg/l decreased to 47% after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 μg/l increased to 33% after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy. PMID:26285696

  20. Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review

    PubMed Central

    2014-01-01

    Anti-Müllerian hormone (AMH) is a very sensitive indicator of the ovarian follicular content. Chemotherapeutic agents are notoriously ovariotoxic in that they damage follicles. The aim of this systematic review was to investigate the interest of serum AMH variations in determining the acute and long-term effects of chemotherapy on the ovarian reserve. According to the PRISMA guidelines, searches were conducted on PubMed for all English language articles until December 2013. Fifteen articles that focused on dynamic variations of AMH levels before and after chemotherapy were selected. Cancer patients have significantly lower AMH after chemotherapy than age-matched controls. Longitudinal studies of AMH variations before, during and after chemotherapy provide information about the degree of follicle loss for each patient according to different chemotherapy regimens. Different patterns of AMH levels during the ovarian recovery phase make it possible to discriminate between high and low gonadotoxic chemotherapy protocols. In addition, pretreatment AMH levels are shown to predict the long-term ovarian function after the end of treatment. These results may help to better understand the ovarian toxicity mechanisms of chemotherapy and to predict the degree of the ovarian follicle loss. Therefore, it can be useful for fertility preservation strategies, fertility counseling and future family planning. PMID:24666685

  1. Peritransplant Serum Albumin Decline Predicts Subsequent Severe Acute Graft-versus-Host Disease after Mucotoxic Myeloablative Conditioning.

    PubMed

    Rashidi, Armin; DiPersio, John F; Westervelt, Peter; Abboud, Camille N; Schroeder, Mark A; Cashen, Amanda F; Pusic, Iskra; Romee, Rizwan

    2016-06-01

    Conditioning-related gut toxicity can result in a protein-losing enteropathy manifesting as a decline in serum albumin in the peritransplant period. Inspired by the pathogenesis of acute graft-versus-host disease (aGVHD), we hypothesized that the magnitude of decline in serum albumin from the day of conditioning initiation until its nadir in the first 2 weeks after hematopoietic cell transplantation HCT (DeltaAlb) predicts the risk for subsequent severe aGVHD. We reviewed the medical records of all 88 patients with acute myeloid leukemia or myelodysplastic syndrome who underwent highly mucotoxic myeloablative (busulfan/cyclophosphamide or cyclophosphamide/total body irradiation) allogeneic HCT from a matched related donor (MRD) or matched unrelated donor (MUD) at our institution between January 1, 2012 and January 1, 2015. Severe aGVHD was associated with MUD (47% versus 14% with MRD; P = .001) and DeltaAlb, which was significantly greater among patients who developed versus did not develop severe aGVHD (1.2 ± .5 versus .8 ± .4 g/dL, respectively; P < .001). In multivariate analysis DeltaAlb remained a significant predictor of severe aGVHD (odds ratio, 5.68; 95% CI, 1.65 to 19.64; P = .006; area under the ROC curve, .74; 95% CI, .63 to .86; P < .001). The best cutoff for DeltaAlb to predict severe aGVHD was .9, with a sensitivity, specificity, and overall classification accuracy of 77%, 66%, and 69%, respectively. The model was validated using the bootstrap technique, with no significant change in its performance. These results were not generalizable to a cohort of 30 patients who received less mucotoxic myeloablative or reduced-intensity conditioning. In conclusion, with mucotoxic myeloablative HCT, each .1-g/dL increase in DeltaAlb was associated with an approximately 23% increase in the odds of developing severe aGVHD. As an early biomarker of gut damage, DeltaAlb can be incorporated in composite risk models for aGVHD prediction, with hopes for

  2. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    PubMed

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function. PMID:26612091

  3. Inflammatory cytokine and acute phase protein concentrations in the peripheral blood and uterine washings of cows with subclinical endometritis in the late postpartum period.

    PubMed

    Brodzki, Piotr; Kostro, Krzysztof; Krakowski, Leszek; Marczuk, Jan

    2015-06-01

    The aim of the study was to evaluate the concentrations of proinflammatory cytokines: tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), anti-inflammatory cytokine interleukin-10 (IL-10), and acute phase proteins (APPs)--haptoglobin (Hp) and serum amyloid A (SAA) in serum and uterine washings of cows with subclinical endometritis, and compare them to healthy animals. The study was performed on 24 cows on day 60 after delivery. The cows were divided into two groups based on the results of cytological tests: 12 cows with subclinical endometritis and 12 healthy cows. Experimental material consisted of blood serum and uterine washings. The levels of the following cytokines in the study material were determined with ELISA: TNF-α, IL-6, IL-10 and APPs - Hp and SAA. The results show that the levels of TNF-α (p < 0.01), IL-6, IL-10 as well as SAA and Hp were significantly higher in the serum of cows with subclinical endometritis compared to the controls (p < 0.001). Uterine washings had significantly higher levels of IL-6, IL-10, and Hp in the experimental cows compared to the controls (p < 0.001). The demonstrated differences in the concentration of cytokines and APP between cows with subclinical endometritis and healthy cows, in both the serum and uterine washings, may suggest the usefulness of these parameters in the diagnosis of subclinical endometritis in cows in the late postpartum period. PMID:25846950

  4. Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl

    PubMed Central

    Doğan, Vehbi; Karaaslan, Erhan; Özer, Samet; Gümüşer, Rüveyda; Yılmaz, Resul

    2016-01-01

    Background: Kawasaki disease is a systemic vasculitis predominately affecting coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of Kawasaki disease have been reported. Case Report: We report here a 4 month-old girl with diffuse coronary ectasia and secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of incomplete Kawasaki disease. Conclusion: Due to the large overlap in clinical symptoms, the presence of atypical findings for Kawasaki disease should suggest the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients. PMID:27606147

  5. The effects of combined therapy of rheumatoid arthritis on the acute phase reactants.

    PubMed

    Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Pllana, Ejup; Dragusha, Gani; Gashi, Masar; Rexhepi, Blerta

    2009-01-01

    The paper presents the results of studies of acute phase reactants in the 60 treated patients with rheumatoid arthritis. Patients were divided into two groups, depending on the applied treatment: group I (n = 30) was treated with methotrexate, sulfasalazine and hydroxychloroquine, and group II (n = 30) with methotrexate. The results of our study shows that there is a statistically significant reduction in the value of acute phase reactants and clinical parameters after treatment in both investigated groups of patients, and also a significant statistical difference between the first and second group of treated patients. PMID:20429264

  6. Phase-Dependent Shifting of the Adrenal Clock by Acute Stress-Induced ACTH.

    PubMed

    Engeland, William C; Yoder, J Marina; Karsten, Carley A; Kofuji, Paulo

    2016-01-01

    The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoid production, yet it is unclear how the clock responds to acute stress. We hypothesized that stress-induced ACTH provides a signal that phase shifts the adrenal clock. To assess whether acute stress phase shifts the adrenal clock in vivo in a phase-dependent manner, mPER2:LUC mice on a 12:12-h light:dark cycle underwent restraint stress for 15 min or no stress at zeitgeber time (ZT) 2 (early subjective day) or at ZT16 (early subjective night). Adrenal explants from mice stressed at ZT2 showed mPER2:LUC rhythms that were phase-advanced by ~2 h, whereas adrenals from mice stressed at ZT16 showed rhythms that were phase-delayed by ~2 h. The biphasic response was also observed in mice injected subcutaneously either with saline or with ACTH at ZT2 or ZT16. Blockade of the ACTH response with the glucocorticoid, dexamethasone, prevented restraint stress-induced phase shifts in the mPER2:LUC rhythm both at ZT2 and at ZT16. The finding that acute stress results in a phase-dependent shift in the adrenal mPER2:LUC rhythm that can be blocked by dexamethasone indicates that stress-induced effectors, including ACTH, act to phase shift the adrenal clock rhythm. PMID:27445984

  7. Phase-Dependent Shifting of the Adrenal Clock by Acute Stress-Induced ACTH

    PubMed Central

    Engeland, William C.; Yoder, J. Marina; Karsten, Carley A.; Kofuji, Paulo

    2016-01-01

    The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoid production, yet it is unclear how the clock responds to acute stress. We hypothesized that stress-induced ACTH provides a signal that phase shifts the adrenal clock. To assess whether acute stress phase shifts the adrenal clock in vivo in a phase-dependent manner, mPER2:LUC mice on a 12:12-h light:dark cycle underwent restraint stress for 15 min or no stress at zeitgeber time (ZT) 2 (early subjective day) or at ZT16 (early subjective night). Adrenal explants from mice stressed at ZT2 showed mPER2:LUC rhythms that were phase-advanced by ~2 h, whereas adrenals from mice stressed at ZT16 showed rhythms that were phase-delayed by ~2 h. The biphasic response was also observed in mice injected subcutaneously either with saline or with ACTH at ZT2 or ZT16. Blockade of the ACTH response with the glucocorticoid, dexamethasone, prevented restraint stress-induced phase shifts in the mPER2:LUC rhythm both at ZT2 and at ZT16. The finding that acute stress results in a phase-dependent shift in the adrenal mPER2:LUC rhythm that can be blocked by dexamethasone indicates that stress-induced effectors, including ACTH, act to phase shift the adrenal clock rhythm. PMID:27445984

  8. Applications of magnetic surface imprinted materials for solid phase extraction of levofloxacin in serum samples.

    PubMed

    Xiao, Deli; Wang, Cuixia; Dai, Hao; Peng, Jun; He, Jia; Zhang, Kai; Kong, Sumei; Qiu, Panzi; He, Hua

    2015-05-01

    In this work, molecularly imprinted magnetic carbon nanotubes (MCNTs@MIPs) was prepared with surface imprinting technique for extraction of levofloxacin in serum samples. The preparation of molecularly imprinted polymers (MIPs) used levofloxacin as template, methacrylic acid as functional monomer, and ethylene glycol dimethacrylate as cross-linker, and the magnetic carbon nanotubes (MCNTs) was synthesized by solvothermal method. The prepared polymers not only can be separated and collected easily by an external magnetic, but also exhibited high specific surface area and high selectivity to template molecules. Kinetic adsorption and static adsorption capacity investigations indicated that the synthesized MCNTs@MIPs had excellent recognition towards levofloxacin. Furthermore, magnetic solid phase extraction (MSPE) using the prepared MCNTs@MIPs as sorbent was then investigated, and an efficient sample cleanup was obtained with recoveries ranged from 78.7 ± 4.8 % to 83.4 ± 4.1%. In addition, several parameters, including the pH of samples, the amount of MCNTs@MIPs, the adsorption and desorption times, and the eluent, were investigated to obtain optimal extraction efficiency. Under the optimal extraction conditions, the stability of the polymer was also evaluated, and the average recovery reduced less than 7.6% after 5 cycles. MCNTs@MIPs successfully applied in the preconcentration and determination of levofloxacin in serum sample suggested that the MSPE method based on the novel polymers could be a promising alternative for selective and efficient extraction of trace amounts of pharmaceutical substances in bio-matrix samples. PMID:25732346

  9. Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients

    PubMed Central

    2013-01-01

    Background Chloride administration has been found to be harmful to the kidney in critically ill patients. However the association between plasma chloride concentration and renal function has never been investigated. Methods This was a retrospective study conducted in a tertiary 24-bed intensive care unit from September 2010 to November 2012. Data on serum chloride for each patient during their ICU stay were abstracted from electronic database. Cl0 referred to the initial chloride on ICU entry, Clmax, Clmin and Clmean referred to the maximum, minimum and mean chloride values before the onset of AKI, respectively. AKI was defined according to the conventional AKIN criteria. Univariate and multivariable analysis were performed to examine the association of chloride and AKI development. Results A total of 1221 patients were included into analysis during study period. Three hundred and fifty-seven patients (29.2%) developed AKI. Clmax was significantly higher in AKI than in non-AKI group (111.8 ± 8.1 vs 107.9 ±5.4 mmol/l; p < 0.001); Cl0 was not significantly different between AKI and non-AKI patients; Clmean was significantly higher in AKI than non-AKI (104.3 ±5.8 vs 103.4 ± 4.5; p = 0.0047) patients. Clmax remained to be associated with AKI in multivariable analysis (OR: 1.10, 95% CI: 1.08-1.13). Conclusion Chloride overload as represented by Clmean and Clmax is significantly associated with the development of AKI. PMID:24164963

  10. Association of Altered Serum MicroRNAs with Perihematomal Edema after Acute Intracerebral Hemorrhage

    PubMed Central

    Zhu, Ying; Wang, Jia-Lu; He, Zhi-Yi; Jin, Feng; Tang, Ling

    2015-01-01

    Background and Purpose Perihematomal edema (PHE) contributes to secondary brain damage and aggravates patient outcomes after intracerebral hemorrhage (ICH). MicroRNAs (miRNAs) are stable in circulation, and their unique expression profiles have fundamental roles in modulating vascular disease. The objective of this study was to test the hypothesis that altered miRNA levels are associated with PHE in ICH patients. Methods Hematoma and PHE volumes of ICH patients were measured on admission and in follow-up computed tomography scans. Whole-genome miRNA profiles of ICH patients and healthy controls were determined using the Exiqon miRCURY LNA Array, and validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatics analysis investigated dysregulated miRNA target genes and the signaling pathways involved. Results We identified 55 miRNAs that were differentially expressed in ICH patients compared with normal controls, of which 54 were down-regulated and one was up-regulated. qRT-PCR confirmation showed decreases in miR-126 (0.63-fold), miR-146a (0.64-fold), miR-let-7a (0.50-fold), and miR-26a (0.54-fold) in ICH patients relative to controls. Serum miR-126, but not miR-146a, miR-let-7a or miR-26a, levels were significantly correlated with relative PHE volume on days 3–4 (r = −0.714; P<0.001) in patients with ICH. Conclusions ICH patients appear to have a specific miRNA expression profile. Low expression of miR-126 was positively correlated with the extent of PHE, suggesting it may have a pathogenic role in the development of PHE after ICH. PMID:26207814

  11. Acute tubular necrosis (ATN) presenting with an unusually prolonged period of marked polyuria heralded by an abrupt oliguric phase

    PubMed Central

    Ramoutar, Virin; Landa, Cristian; James, Leighton R

    2014-01-01

    A 50-year-old African-American man presented with acute tubular necrosis (ATN) secondary to hypotension from non-typhoid Salmonella gastroenteritis and bacteraemia. The oliguric phase lasted only 24 h followed by prolonged polyuria for 20 days, with urine output in excess of 16 L/day at maximum. As indexed in PubMed this is only the second published case of this nature since 1974, in which an abrupt oliguric phase of 24 h or less heralded prolonged polyuria in ATN. The diagnosis is challenging as fractional excretion of sodium early in the clinical course and rapid normalisation of serum creatinine with intravenous fluids (IVF) may point towards prerenal azotaemia resulting in a premature discharge from hospital. Patients with an abrupt oliguric phase may suffer a secondary renal insult from the profound fluid loss that is to follow and may need inpatient monitoring with supplemental IVF to prevent deleterious outcomes. PMID:25150229

  12. Differentiation of acute renal failure and chronic renal failure by 2-dimensional analysis of urinary dipeptidase versus serum creatinine.

    PubMed

    Lee, S H; Kang, B Y; We, J S; Park, S K; Park, H S

    1999-03-01

    The differential diagnosis of acute renal failure (ARF) and chronic renal failure (CRF) may be possible by measuring urinary dipeptidase (Udpase) activity and serum creatinine (Scr) concentration. When the mass test of 246 individuals was examined on a 2-dimensional plot of Udpase (y-axis) versus Scr (x-axis) with the data obtained from healthy volunteers (n = 189), ARF (n = 19) and CRF (n = 38) patients, the characteristic distribution of each group was obvious. It is summarized by the mean values of healthy volunteers (1.44 +/- 0.39 mg/dL, 1.19 (0.59 mU/mL), ARF (6.04 +/- 5.04 mg/dL, 0.12 +/- 0.08 mU/mL), and CRF patients (8.72 +/- 2.93 mg/dL, 0.81 +/- 0.44 mU/mL). The healthy volunteers are distributed along the y-axis and the ARF patients the x-axis, thus separating the two groups 90 degrees apart. The CRF patients are scattered away from both x-, and y-axis. This 2-dimensional approach is thought to be very useful for the differential diagnosis of ARF suggesting Udpase as a new member of the marker enzymes of renal disease. PMID:10088177

  13. GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-12-03

    Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. Serum Neutrophil Gelatinase-Associated Lipocalin in Infants and Children with Sepsis-Related Conditions with or without Acute Renal Dysfunction

    PubMed Central

    Afify, Mohammed Farouk M.; Maher, Sheren Esam; Ibrahim, Nora Mohamed; El-Hamied, Waleed Mahamoud Abd

    2016-01-01

    PURPOSE To validate serum neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for acute kidney injury (AKI) in sepsis-related conditions and its predictive and prognostic values. PATIENTS AND METHODS This study included 65 patients, who were clinically evaluated for sepsis, severe sepsis, or septic shock, and 20 apparently healthy served as controls. Patients were divided into two groups: Group I (AKI-sepsis): 65 newly admitted patients diagnosed as sepsis, who were further divided into three subgroups according to the severity: systemic inflammatory response syndrome, severe sepsis, and septic shock, and Group II (control group): 20 apparently healthy subjects matched for age and sex, serum creatinine and serum NGAL concentrations were estimated initially within 24 hours of admission and after 72 hours of admission in all patients and control groups. RESULTS Serum NGAL increased significantly with increasing severity of renal impairment. Receiver-operating characteristic analysis suggested that serum NGAL cutoff value of 40 ng/mL within the first 24 hours of admission is highly specific and sensitive for predicting AKI, with sensitivity of 90.9% and specificity of 75.8%. CONCLUSION We concluded that early measurement of serum NGAL level in sepsis can serve as a clinically useful marker for early prediction of AKI and for grading of its severity. PMID:27547045

  15. Elevated serum levels of IGFBP-2 found in children suffering from acute leukaemia is accompanied by the occurrence of IGFBP-2 mRNA in the tumour clone.

    PubMed Central

    Wex, H.; Vorwerk, P.; Mohnike, K.; Bretschneider, D.; Kluba, U.; Aumann, V.; Blum, W. F.; Mittler, U.

    1998-01-01

    Insulin-like growth factor-binding proteins (IGFBPs) are important modulators of IGF action. In 50 children suffering from acute lymphoblastic leukaemia (ALL), we studied the serum levels of IGFBP-1,-2 and-3. The mean standard deviation score (SDS) values were estimated to be 0.7, 3.1 and -1.7 for the IGFBP-1,-2 and-3, respectively, compared with the normal range defined by a SDS from -2 to +2. IGFBP-1 and-3 were normal, but for IGFBP-2 we found a significantly elevated serum level compared with control groups (P < 0.05). However, during chemotherapy this increased serum IGFBP-2 normalized. In addition, we found a correlation between higher serum levels and the detection rate of the IGFBP-2 transcript in corresponding cells. In patients with ALL, the detection rates of IGFBP-2 mRNA were estimated to be 72% and 35% at the time of diagnosis and at day 33 of chemotherapy respectively; in the control groups (healthy children and children at their initial presentation of diabetes mellitus), the values were 28% and 33% respectively. Based on the correlation between IGFBP-2 serum levels and the corresponding gene expression as well as the normalization of IGFBP-2 levels during chemotherapy, we concluded that the increased serum level mainly originated from the tumour clone itself. Furthermore, possible functional consequences of elevated IGFBP-2 were outlined. Images Figure 2 Figure 3 PMID:9716037

  16. Proteins involved on TGF-β pathway are up-regulated during the acute phase of experimental Chagas disease.

    PubMed

    Ferreira, Roberto Rodrigues; de Souza, Elen Mello; de Oliveira, Fabiane Loiola; Ferrão, Patrícia Mello; Gomes, Leonardo Henrique Ferreira; Mendonça-Lima, Leila; Meuser-Batista, Marcelo; Bailly, Sabine; Feige, Jean Jacques; de Araujo-Jorge, Tania Cremonini; Waghabi, Mariana Caldas

    2016-05-01

    Studies developed by our group in the last years have shown the involvement of TGF-β in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-β cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-β is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-β signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-β receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-β. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-β activity in the heart, we found that serum levels of total TGF-β were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-β pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection. PMID:26852285

  17. Modulation of the acute phase response in feedlot steers supplemented with Saccharomyces cerevisiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of supplementing feedlot steers with Saccharomyces cerevisiae CNCM I-1079 (SC) on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 266 ± 4 kilograms body weight) were separated into three treatment groups (n = 6/treatm...

  18. Altered postnatal acute phase response in heifers exposed to lipopolysachcharide in utero

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to LPS challenge in heifer calves. Pregnant crossbred cows (n=50) were separated into prenatal stress (PNS; n=25; administered 0.1 microgram per kilogram...

  19. Changes in the Neuropsychological Correlates of Clinical Dimensions between the Acute and Stable Phase of Schizophrenia

    ERIC Educational Resources Information Center

    Guillem, F.; Ganeva, E.; Pampoulova, T.; Stip, E.; Lalonde, P.; Sasseville, M.

    2005-01-01

    This study was designed to investigate whether the neuropsychological correlates of the symptom dimensions of schizophrenia vary with the clinical state in patients followed from the acute to stable the phase of the illness. Fifteen patients were assessed for symptoms (SAPS-SANS) and undergone a complete neuropsychological assessment at two…

  20. Angus and Romosinuano steers exhibit differential acute phase responses following an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our primary objective was to elucidate the acute phase response in cattle while evaluating potential genetic differences between two diverse Bos taurus breeds [Angus (AG) and Romosinuano (RO)] in response to an endotoxin challenge. The Romosinuano is a tropically adapted Bos taurus breed developed i...

  1. Roles of STAT3 in Protein Secretion Pathways during the Acute-Phase Response

    PubMed Central

    Ahyi, Ayele-Nati N.; Quinton, Lee J.; Jones, Matthew R.; Ferrari, Joseph D.; Pepper-Cunningham, Zachary A.; Mella, Juan R.; Remick, Daniel G.

    2013-01-01

    The acute-phase response is characteristic of perhaps all infections, including bacterial pneumonia. In conjunction with the acute-phase response, additional biological pathways are induced in the liver and are dependent on the transcription factors STAT3 and NF-κB, but these responses are poorly understood. Here, we demonstrate that pneumococcal pneumonia and other severe infections increase expression of multiple components of the cellular secretory machinery in the mouse liver, including the endoplasmic reticulum (ER) translocon complex, which mediates protein translation into the ER, and the coat protein complexes (COPI and COPII), which mediate vesicular transport of proteins to and from the ER. Hepatocyte-specific mutation of STAT3 prevented the induction of these secretory pathways during pneumonia, with similar results observed following pharmacological activation of ER stress by using tunicamycin. These findings implicate STAT3 in the unfolded protein response and suggest that STAT3-dependent optimization of secretion may apply broadly. Pneumonia also stimulated the binding of phosphorylated STAT3 to promoter regions of secretion-related genes in the liver, supporting a direct role for STAT3 in their transcription. Altogether, these results identify a novel function of STAT3 during the acute-phase response, namely, the induction of secretory machinery in hepatocytes. This may facilitate the processing and delivery of newly synthesized loads of acute-phase proteins, enhancing innate immunity and preventing liver injury during infection. PMID:23460517

  2. Early weaning alters the acute phase response to an endotoxin challenge in beef calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research indicates that early weaning prior to shipment can reduce transportation-induced increases in acute phase proteins (APP), and can increase subsequent performance in the feedlot. These data suggest that the combination of weaning and transport stress may compromise the immune system...

  3. Profile of the bovine acute-phase response following an intravenous bolus-dose lipopolysaccharide challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two experiments were conducted to further define the acute-phase response to a lipopolysaccharide (LPS) challenge in beef steers. In Exp. 1, 9 crossbred beef steers (449 ± 12 kg BW) were used in a completely random design to determine the effects of 0.5, 1.0, or 2.0 micrograms of LPS/kilogram of bod...

  4. Increasing and decreasing phases of ferritin and hemosiderin iron determined by serum ferritin kinetics.

    PubMed

    Saito, Hiroshi; Hayashi, Hisao; Tomita, Akihiro; Ohashi, Haruhiko; Maeda, Hideaki; Naoe, Tomoki

    2013-08-01

    We attempted to clarify the mechanism of the storage iron metabolism. A new program of serum ferritin kinetics was applied for studying the increasing and decreasing phases of ferritin and hemosiderin iron in iron addition and removal in patients with a normal level of iron stores or iron overload. The change of ferritin iron in response to iron addition and removal was rapid in the initial stage, but it was slow later. In contrast, the change of hemosiderin iron was slow in the initial stage, but it became rapid later. These changes of ferritin and hemosiderin iron suggest that the turnover of ferritin iron is preferential to that of hemosiderin iron, and that the initially existed ferritin iron is gradually replaced by the ferritin iron recovered by taking iron from hemosiderin in iron mobilization. The crossing of the increasing curves of ferritin and hemosiderin iron in iron addition indicates a switching of the principal storage iron from ferritin to hemosiderin. The crossing point shifted toward a higher storage iron level in the increase of iron deposition. Iron storing capacity can be increased not only by the transformation of ferritin into hemosiderin, but also by the expansion of cell space as seen by hepatomegaly in hereditary hemochromatosis. The amounts of hemosiderin iron exceeded ferritin iron in all 10 patients with chronic hepatitis C even though they had normal storage iron levels. This suggests it is difficult to store iron in the form of ferritin in chronic hepatitis C. PMID:24640177

  5. Characterization of bovine serum albumin partitioning behaviors in polymer-salt aqueous two-phase systems.

    PubMed

    Chow, Yin Hui; Yap, Yee Jiun; Tan, Chin Ping; Anuar, Mohd Shamsul; Tejo, Bimo Ario; Show, Pau Loke; Ariff, Arbakariya Bin; Ng, Eng-Poh; Ling, Tau Chuan

    2015-07-01

    In this paper, a linear relationship is proposed relating the natural logarithm of partition coefficient, ln K for protein partitioning in poly (ethylene glycol) (PEG)-phosphate aqueous two-phase system (ATPS) to the square of tie-line length (TLL(2)). This relationship provides good fits (r(2) > 0.98) to the partition of bovine serum albumin (BSA) in PEG (1450 g/mol, 2000 g/mol, 3350 g/mol, and 4000 g/mol)-phosphate ATPS with TLL of 25.0-50.0% (w/w) at pH 7.0. Results also showed that the plot of ln K against pH for BSA partitioning in the ATPS containing 33.0% (w/w) PEG1450 and 8.0% (w/w) phosphate with varied working pH between 6.0 and 9.0 exhibited a linear relationship which is in good agreement (r(2) = 0.94) with the proposed relationship, ln K = α' pH + β'. These results suggested that both the relationships proposed could be applied to correlate and elucidate the partition behavior of biomolecules in the polymer-salt ATPS. The influence of other system parameters on the partition behavior of BSA was also investigated. An optimum BSA yield of 90.80% in the top phase and K of 2.40 was achieved in an ATPS constituted with 33.0% (w/w) PEG 1450 and 8.0% (w/w) phosphate in the presence of 8.5% (w/w) sodium chloride (NaCl) at pH 9.0 for 0.3% (w/w) BSA load. PMID:25553974

  6. Simple and rapid solid-phase radioimmunoassay for serum progesterone, using the protein A of Staphylococcus aureus as immunoadsorbent

    SciTech Connect

    Jungers, J.; Delogne-Desnoeck, J.; Robyn, C.

    1981-07-01

    A simple, rapid, and inexpensive radioimmunoassay method for serum progesterone is described, which uses a solid-phase technique for separation of antibody-bound from antibody-free progesterone. Rabbit antiprogesterone immunoglobulins are adsorbed on the protein A of formaldehyde- and heat-treated Staphylococcus aureus cells (Pansorbin; Calbiochem-Behring Corp., La Jolla, California). The suspension of antibody-coated Pansorbin retains all its binding activity of 1-2-H(N)-progesterone when kept at + 4/sup 0/ or at -25/sup 0/C for at least 4 months. Dose-response curves obtained with ether-serum extracts and with the progesterone standard do not deviate significantly from parallelism. The progesterone standard gives identical dose-response curves whether diluted in the assay buffer or in a progesterone-free ether-serum extract. The sensitivity of the assay is 0.02 ng/assay tube. The intra-assay variation coefficient is 16%, and the routine interassay variation coefficient is 17%. The mean serum progesterone concentrations were 0.55 ng/ml during the follicular phase of the menstrual cycle and 12.5 ng/ml during the luteal phase. The average blank value for distilled water was 0.02 ng/assay tube.

  7. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  8. Metabolizable protein supply modulated the acute-phase response following vaccination of beef steers.

    PubMed

    Moriel, P; Arthington, J D

    2013-12-01

    Our objective was to evaluate the effects of MP supply, through RUP supplementation, on the acute-phase response of beef steers following vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 ± 31 kg; 175 ± 16 d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining 0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and individually provided to steers once daily (0800 h) from d 0 to 29. Steers were weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d 7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and ADG were similar (P ≥ 0.50) among treatments (mean = 184 ± 9 kg and 0.5 ± 0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma concentrations of all acute-phase proteins, which peaked between d 7 to 14, returning to baseline concentrations by d 29. Treatment effects were not detected (P ≥ 0.19) for plasma concentrations of acid-soluble protein, albumin, fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein (TP) and plasma urea nitrogen (PUN) increased (P ≤ 0.05) with increasing supply of MP (87.1, 89.6, and 90.1 ± 1.09 mg TP/mL and 6.1, 8.3, and 10.3 ± 0.41 mg PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations. On d 14, plasma concentrations of haptoglobin were greatest (P ≤ 0.06) for steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71 and 0.44 ± 0.099 mg/mL, respectively). On d 10, plasma concentrations of creatinine were greater (P = 0.01) for steers

  9. Application of high-performance thin-layer chromatography for the detection of organophosphorus insecticides in human serum after acute poisoning.

    PubMed

    Futagami, K; Narazaki, C; Kataoka, Y; Shuto, H; Oishi, R

    1997-12-19

    We developed a rapid and simple method for identifying 25 commonly used organophosphorus insecticides in human serum using high-performance thin-layer chromatography (HPTLC). These organophosphates were separated on plates with three different developing systems within 6-18 min and detected by means of ultraviolet radiation and coloring reactions with 4-(4-nitrobenzyl)pyridine-tetraethylenepentamine reagent (NT reagent) or palladium chloride reagent (PdCl2 reagent). Each organophosphate was accurately identified by means of the R(F) x 100 value and the spot color in three systems. The detection limits of dichlorvos, fenitrothion, malathion, methidathion, parathion and trichlorfon in serum by the liquid-liquid extraction method were 1.1, 0.12, 0.12, 0.05, 0.6 and 0.1 microg/ml, respectively. These sensitivities may be sufficient to detect those organophosphates in patient serum after acute poisoning. PMID:9518173

  10. Discordant uptake of Tc-99m DTPA-galactosyl human serum albumin and Tc-99m Sn colloid in a patient with severe acute hepatitis.

    PubMed

    Miyazaki, C; Matsunaga, T; Kubo, K

    1994-08-01

    A patient with recently diagnosed severe acute hepatitis underwent serial liver scintigraphy with Tc-99m Sn colloid and Tc-99m DTPA-galactosyl human serum albumin. In initial studies, radionuclide distribution on Tc-99m DTPA-galactosyl human serum albumin scintigraphy was completely discrepant to that on Tc-99m Sn colloid scintigraphy. In a follow-up study 1 month later, the distribution of both radionuclides in the liver appeared relatively homogeneous. The uptake of Tc-99m DTPA-galactosyl human serum albumin and Tc-99m Sn colloid reflects the function of hepatocytes and Kupffer cells, respectively. Both kinds of scintigraphic study may be helpful to assess histopathologic change of different hepatic tissue architectures. PMID:7955747

  11. Early phase combined therapeutic management of acute ischaemic stroke.

    PubMed

    Bassi, P; Lattuada, P; Tonietti, S

    2005-05-01

    An adequate treatment of ischaemic stroke in the early phase (28-48 h) is the most important factor for a better outcome. Thrombolysis with rTPA (within 3 h) and oral ASA 300 mg/days are the first therapeutic misures. Continuous monitoring of cardiological and haemodinamic parameters allows early detection of cardiac disturbances. Treatment of hypertension, low haematic oxigenation, hyperglicaemia, seizures and hypertermia is basic to improve outcome. Pharmacological therapy is only one of the components of effective multidisciplinary integrated management of ischaemic stroke; we remind also the precocity of rehabilitation procedures and an accurate psychological assessment. PMID:15883687

  12. Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study

    PubMed Central

    2013-01-01

    Introduction 30 day mortality in patients with Acute Respiratory Failure (ARF) is approximately 30%, defined as patients requiring ventilator support for more than 6 hours. Novel biomarkers are needed to predict patient outcomes and to guide potential future therapies. The activins A and B, members of the Transforming Growth Factor β family of proteins, and their binding protein, follistatin, have recently been shown to be important regulators of inflammation and fibrosis but no substantial data are available concerning their roles in ARF. Our objectives were to evaluate whether the serum levels of activin A, B and follistatin are elevated in 518 patients with ARF from the FINNALI study compared the concentrations in 138 normal subjects that form a reference range. Methods Specific assays for activin A, B and follistatin were used and the results analyzed according to diagnostic groups as well as according to standard measures in intensive care. Multivariable logistic regression was used to create a model to predict death at 90 days and 12 months from the onset of the ARF. Results Serum activin A and B were significantly elevated in most patients and in most of the diagnostic groups. Patients who had activin A and/or B concentrations above the reference maximum were significantly more likely to die in the 12 months following admission [either activin A or B above reference maximum: Positive Likelihood Ratio [LR+] 1.65 [95% CI 1.28-2.12, P = 0.00013]; both activin A and B above reference maximum: LR + 2.78 [95% CI 1.96-3.95, P < 0.00001]. The predictive model at 12 months had an overall accuracy of 80.2% [95% CI 76.6-83.3%]. Conclusions The measurement of activin A and B levels in these patients with ARF would have assisted in predicting those at greatest risk of death. Given the existing data from animal studies linking high activin A levels to significant inflammatory challenges, the results from this study suggest that approaches to modulate

  13. Serum miRNA-499 and miRNA-210: A potential role in early diagnosis of acute coronary syndrome.

    PubMed

    Shalaby, Sally M; El-Shal, Amal S; Shoukry, Amira; Khedr, Mohamad H; Abdelraheim, Nader

    2016-08-01

    In clinical practice, there is still a need for novel biomarkers, which can reliably rule in or rule out acute coronary syndrome (ACS) immediately on admission. This is of particular interest in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) in whom diagnostic uncertainty is high. The aim of the present study is to evaluate the potential role of miRNA-499 and miRNA-210 as novel molecular biomarkers for early diagnosis of UA and NSTEMI suspected patients presented at the emergency unit. A total of 110 patients presenting to the intensive care unit (ICU) within 24 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 37 UA, 48 NSTEMI and 25 noncardiac chest pain (NCCP) patients. Immediately at enrollment, blood samples were taken for estimation of serum miRNA-499 and miRNA-210 expression levels by real time PCR. miRNA-499 and miRNA-210 expression levels were significantly increased in UA and NSTEMI patients compared with NCCP patients (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that the area under curve (AUC) of miR-499 for the diagnosis of UA and NSTEMI was 0.98 and 0.97, respectively; while the AUC of miRNA-210 was 0.84 and 0.90, respectively. The important finding of our study was that the AUC of miRNA-499 for the diagnosis of ACS patients with symptoms onset <3 h was 0.89, while the AUC of miRNA-210 was 0.86. Interestingly, combining miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.96, P < 0.001. In conclusion, serum miRNA-499 and miRNA-210 are associated with UA and NSTEMI and with those presenting within 3 h of symptom onset. Both miRNAs might be potentially novel biomarkers for accelerating the diagnosis of ACS patients in emergency unit. © 2016 IUBMB Life, 68(8):673-682, 2016. PMID:27346801

  14. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

    PubMed

    Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

    2014-01-01

    Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I. PMID:25299597

  15. Lipopolysaccharide-induced anti-inflammatory acute phase response is enhanced in spermidine/spermine N1-acetyltransferase (SSAT) overexpressing mice.

    PubMed

    Pirnes-Karhu, Sini; Sironen, Reijo; Alhonen, Leena; Uimari, Anne

    2012-02-01

    Bacterial lipopolysaccharide (LPS) is an effective activator of the components of innate immunity. It has been shown that polyamines and their metabolic enzymes affect the LPS-induced immune response by modulating both pro- and anti-inflammatory actions. On the other hand, LPS causes changes in cellular polyamine metabolism. In this study, the LPS-induced inflammatory response in spermidine/spermine N(1)-acetyltransferase overexpressing transgenic mice (SSAT mice) was analyzed. In liver and kidneys, LPS enhanced the activity of the polyamine biosynthetic enzyme ornithine decarboxylase and increased the intracellular putrescine content in both SSAT overexpressing and wild-type mice. In survival studies, the enhanced polyamine catabolism and concomitantly altered cellular polyamine pools in SSAT mice did not affect the LPS-induced mortality of these animals. However, in the acute phase of LPS-induced inflammatory response, the serum levels of proinflammatory cytokines interleukin-1β and interferon-γ were significantly reduced and, on the contrary, anti-inflammatory cytokine interleukin-10 was significantly increased in the sera of SSAT mice compared with the wild-type animals. In addition, hepatic acute-phase proteins C-reactive protein, haptoglobin and α(1)-acid glycoprotein were expressed in higher amounts in SSAT mice than in the wild-type animals. In summary, the study suggests that SSAT overexpression obtained in SSAT mice enhances the anti-inflammatory actions in the acute phase of LPS-induced immune response. PMID:21814792

  16. Mass-Spectrometric Identification of T-Kininogen I/Thiostatin as an Acute-Phase Inflammatory Protein Suppressed by Curcumin and Capsaicin

    PubMed Central

    Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R.; Basrur, Venkatesha; Lokesh, Belur R.

    2014-01-01

    Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I. PMID:25299597

  17. Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis.

    PubMed

    Okuda, Ryo; Matsushima, Hidekazu; Aoshiba, Kazutetsu; Oba, Tomohiro; Kawabe, Rie; Honda, Koujiro; Amano, Masako

    2015-01-01

    The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other interstitial pneumonia markers were measured. In this study, 30 patients with stable IPF and 11 patients with acute exacerbation of IPF were collected. Mean sICAM-1 levels were 434 ± 139 ng/mL for the stable phase of IPF, 645 ± 247 ng/mL for early phase of acute exacerbation of IPF, 534 ± 223 ng/mL for connective tissue disease-associated interstitial pneumonia, 221 ± 42 for chronic obstructive pulmonary disease, and 150 ± 32 ng/mL in healthy volunteers. For the stable phase of IPF, sICAM-1 levels correlated with Krebs von den Lungen-6 (KL-6) (r value: 0.41; p value: 0.036). Mean sICAM-1 levels were significantly higher in patients with early phase of acute exacerbation of IPF than with stable phase of IPF (p = 0.0199). Multiple logistic analyses indicated that the predictors for early phase of acute exacerbation of IPF were only sICAM-1 and C-reactive protein (odds ratio: 1.0093; 1.6069). In patients with stable IPF, sICAM-1 levels correlated with KL-6; sICAM-1 might be a predictive indicator for prognosis. In the early phase of acute exacerbation of IPF, sICAM-1 might be more useful for diagnosis than other interstitial pneumonia markers. PMID:26543791

  18. Characterization of an intravenous lipopolysaccharide inflammation model in calves with respect to the acute-phase response.

    PubMed

    Plessers, Elke; Wyns, Heidi; Watteyn, Anneleen; Pardon, Bart; De Backer, Patrick; Croubels, Siska

    2015-01-15

    Our objective was to develop a lipopolysaccharide (LPS) inflammation model in calves to evaluate the acute-phase response with respect to the release of pro-inflammatory cytokines and acute-phase proteins, fever development and sickness behaviour. Fourteen 4-week-old male Holstein Friesian calves were included and randomly assigned to a negative control group (n=3) and an LPS-challenged group (n=11). The latter received an intravenous bolus injection of 0.5 μg of LPS/kg body weight. Blood collection and clinical scoring were performed at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 28, 32, 48, 54 and 72 h post LPS administration (p.a.). In the LPS group, the following clinical signs were observed successively: tachypnoea (on average 18 min p.a.), decubitus (29 min p.a.), general depression (1.75 h p.a.), fever (5h p.a.) and tachycardia (5h p.a.). Subsequent to the recovery from respiratory distress, general depression was prominent, which deteriorated when fever increased. One animal did not survive LPS administration, whereas the other animals recovered on average within 6.1h p.a. Moreover, the challenge significantly increased plasma concentrations of tumour necrosis factor-α, interleukin 6, serum amyloid A and haptoglobin, with peaking levels at 1, 3.5, 24 and 18 h p.a., respectively. The present LPS model was practical and reproducible, caused obvious clinical signs related to endotoxemia and a marked change in the studied inflammatory mediators, making it a suitable model to study the immunomodulatory properties of drugs in future research. PMID:25534079

  19. Yeast cell wall supplementation alters aspects of the physiological and acute phase responses of crossbred heifers to an endotoxin challenge.

    PubMed

    Burdick Sanchez, Nicole C; Young, Tanner R; Carroll, Jeffery A; Corley, Jimmie R; Rathmann, Ryan J; Johnson, Bradley J

    2013-01-01

    A study was conducted to determine the effect of feeding yeast cell wall (YCW) products on the physiological and acute phase responses of crossbred, newly-received feedlot heifers to an endotoxin challenge. Heifers (n = 24; 219 ± 2.4 kg) were separated into treatment groups receiving either a control diet (n = 8), YCW-A (2.5 g/heifer/d; n = 8) or YCW-C (2.5 g/heifer/d; n = 8) and were fed for 52 d. On d 37 heifers were challenged i.v. with LPS (0.5 µg/kg body mass) and blood samples were collected from -2 h to 8 h and again at 24 h relative to LPS challenge. There was an increase in vaginal temperature in all heifers post-LPS, with YCW-C maintaining a lower vaginal temperature post-LPS than control and YCW-A heifers. Sickness behavior scores increased post-LPS in all heifers, but were not affected by treatment. Cortisol concentrations were greatest in control heifers post-LPS compared with YCW-A or YCW-C heifers. Concentrations of IFN-γ and TNF-α increased post-LPS, but were not affected by treatment. Serum IL-6 concentrations increased post-LPS and were greater in control heifers than YCW-A and YCW-C heifers. These data indicate that YCW supplementation can decrease the physiological and acute phase responses of newly-received heifers following an endotoxin challenge. PMID:23288885

  20. Suppression of DHEA sulfotransferase (Sult2A1) during the acute-phase response.

    PubMed

    Kim, Min Sun; Shigenaga, Judy; Moser, Art; Grunfeld, Carl; Feingold, Kenneth R

    2004-10-01

    The acute-phase response (APR) induces alterations in lipid metabolism, and our data suggest that this is associated with suppression of type II nuclear hormone receptors that are key regulators of fatty acid, cholesterol, and bile acid metabolism. Recently, the farnesoid X receptor (FXR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) were found to regulate DHEA sulfotransferase (Sult2A1), which plays an important role in DHEA sulfation and detoxification of bile acids. Because FXR, PXR, and CAR are suppressed during the APR, we hypothesized that Sult2A1 is downregulated during the APR. To induce the APR, mice were treated with LPS, which will then trigger the release of various cytokines, and the mRNA levels of Sult2A1 and the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2), as well as the enzyme activity of Sult2A1, were determined in the liver. We found that mRNA levels of Sult2A1 decrease in a time- and dose-dependent manner during the LPS-induced APR. Similar changes were observed in the mRNA levels of PAPSS2, the major synthase of PAPS in the liver. Moreover, hepatic Sult2A1 activity and serum levels of DHEA-sulfate (DHEA-S) were significantly decreased in LPS-treated animals. These results suggest that decreased levels or activities of FXR, PXR, and CAR during the APR could contribute to decreases in Sult2A1, resulting in decreased sulfation of DHEA and lower circulating level of DHEA-S. Finally, we found that both TNF and IL-1 caused a significant decrease in the mRNA level of Sult2A1 in Hep3B human hepatoma cells, suggesting that the proinflammatory cytokines TNF and IL-1 mediate the inhibitory effect of LPS on Sult2A1 mRNA level. Our study provides a possible mechanism by which infection and inflammation are associated with altered steroid metabolism and cholestasis. PMID:15198932

  1. Aripiprazole in the acute and maintenance phase of bipolar I disorder

    PubMed Central

    Zupancic, Melanie; Gonzalez, Misty L

    2012-01-01

    Bipolar affective disorder is a disabling illness with substantial morbidity and many management challenges. Traditional mood stabilizers such as lithium, valproate, and carbamazepine are often inadequate in controlling symptoms both during the acute and maintenance phase of treatment. Aripiprazole is a second-generation antipsychotic with a unique mechanism of action. Evidence suggests that it is effective in acute manic and mixed states. There are limited data to suggest its efficacy as a maintenance agent. Future studies will be needed to better define the role of aripiprazole relative to other traditional pharmacologic agents. PMID:22298948

  2. Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

    PubMed Central

    2014-01-01

    Scientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response (APR) following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) or liquid chromatography–mass spectrometry (LC-MS/MS) are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and most recently proteomic methods have been used to

  3. ACUTE ETHANOL DISRUPTS PHOTIC AND SEROTONERGIC CIRCADIAN CLOCK PHASE-RESETTING IN THE MOUSE

    PubMed Central

    Brager, Allison J.; Ruby, Christina L.; Prosser, Rebecca A.; Glass, J. David

    2011-01-01

    Background Alcohol abuse is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol abuse on the circadian timing system. In this study, we extend previous work in C57BL/6J mice to: 1) characterize the SCN pharmacokinetics of acute systemic ethanol administration; 2) explore the effects of acute ethanol on photic and non-photic phase-resetting; and 2) determine if the SCN is a direct target for photic effects. Methods First, microdialysis was used to characterize the pharmacokinetics of acute i.p. injections of 3 doses of ethanol (0.5, 1.0 and 2.0 g/kg) in the mouse suprachiasmatic (SCN) circadian clock. Second, the effects of acute i.p. ethanol administration on photic phase-delays and serotonergic ([+]8-OH-DPAT-induced) phase-advances of the circadian activity rhythm were assessed. Third, the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized. Results Peak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20–40 min post-injection with half-lives for clearance ranging from 0.6–1.8 hr. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase-delays. Conclusions These results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and non-photic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral, physiological, and endocrine rhythms associated with alcoholism. PMID:21463340

  4. Effect of bone marrow mesenchymal stem cells transplantation on the serum and liver HMGB1 expression in rats with acute liver failure

    PubMed Central

    Zheng, Sheng; Yang, Juan; Tang, Yingmei; Yang, Jinhui; Shao, Qinghua; Guo, Ling; Liu, Qinghua

    2015-01-01

    Objective: This study aimed to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of high mobility group box 1 protein (HMGB1) in the serum and liver of rats with acute liver failure (ALF). Methods: Healthy male SD rats were randomly divided into control group, ALF group and BMSCs group. ALF was induced by intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS. In BMSCs group, rats received BMSCs (1.0×107) transplantation via the tail vein at 2 h after ALF induction. Results: Intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS was able to induce ALF in rats. In ALF group, serum ALT and AST increased gradually over time. At 72 h, the serum ALT and AST in BMSCs group were significantly different from those in ALF group. HMGB1 expression in the serum and liver remained at a low level at any time point in control group, but increased significantly in ALF group and BMSCs group. The serum and liver HMGB1 expression increased progressively in ALF group, but reduced gradually in BMSCs group. Significant difference in serum and liver HMGB1 expression was observed between ALF group and BMSCs group at 24 h and 72 h. In addition, there was marked difference in the survival rate among three groups at 24 h (χ2=21.098, P<0.01). Conclusion: BMSCs transplantation is able to improve the liver function and liver pathology in ALF rats and decrease the serum and liver HMGB1. PMID:26884873

  5. Tricuspid and mitral regurgitation detected by color flow Doppler in the acute phase of Kawasaki disease

    SciTech Connect

    Suzuki, A.; Kamiya, T.; Tsuchiya, K.; Sato, I.; Arakaki, Y.; Kohata, T.; Ono, Y.

    1988-02-01

    Valvular lesions in the acute phase of Kawasaki disease were studied in 19 children. The patients were intensively observed by color flow Doppler every day from the day of hospitalization up to 12 days after the onset of the disease and 2 or more times a week thereafter, for up to 28 days. Mitral regurgitation (MR) was found in 9 patients (47%) and tricuspid regurgitation (TR) in 10 (53%). MRs were of transient type and confirmed from 7.5 +/- 1.6 (mean +/- standard deviation) to 13.1 +/- 6.5 days after the onset of the disease. Both types of valvular regurgitation were mild. The direction of regurgitation was from the center of valvular coaptation toward the posterior wall of the atrium. Neither valvular prolapse nor valvular deformity was noted. In patients with MR, left ventricular ejection fraction on M-mode echocardiography was significantly lower in the acute phase than in the convalescent phase of the disease (p less than 0.05). Using gallium-67 scintigram, the positive uptake of the isotope was noted in 7 (88%) of 8 patients with MR, but not found at all in 8 patients free of MR. These results suggest that MR and TR are often transient in the acute phase of Kawasaki disease and could be attributed to myocarditis.

  6. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    PubMed Central

    2011-01-01

    Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

  7. Dietary β-glucan stimulate complement and C-reactive protein acute phase responses in common carp (Cyprinus carpio) during an Aeromonas salmonicida infection.

    PubMed

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna; Frost, Patrick; Irnazarow, Ilgiz; Shrive, Annette; Hoole, Dave

    2013-03-01

    The effect of β-glucans as feed additive on the profile of C-reactive protein (CRP) and complement acute phase responses was studied in common carp Cyprinus carpio after exposition to a bacterial infection with Aeromonas salmonicida. Carp were orally administered with β-glucan (MacroGard®) for 14 days with a daily β-glucan intake of 6 mg per kg body weight. Fish were then intraperitoneally injected with either PBS or 1 × 10⁸ bacteria per fish and sampled at time 0, 6, 12, 24, 48, 72, 96 and 120 h post-injection (p.i.) for serum and head kidney, liver and mid-gut tissues. CRP levels and complement activity were determined in the serum samples whilst the gene expression profiles of CRP and complement related genes (crp1, crp2, c1r/s, bf/c2, c3 and masp2) were analysed in the tissues by quantitative PCR. Results obtained showed that oral administration of β-glucan for 14 days significantly increased serum CRP levels up to 2 fold and serum alternative complement activity (ACP) up to 35 fold. The bacterial infection on its own (i.e. not combined with a β-glucan feeding) did have significant effects on complement response whilst CRP was not detectably induced during the carp acute phase reaction. However, the combination of the infection and the β-glucan feeding did show significant effects on both CRP and complement profiles with higher serum CRP levels and serum ACP activity in the β-glucan fed fish than in the control fed fish. In addition, a distinct organ and time dependent expression profile pattern was detected for all the selected genes: a peak of gene expression first occurred in the head kidney tissue (6 h p.i. or 12 h p.i.), then an up-regulation in the liver several hours later (24 h p.i.) and finally up- or down-regulations in the mid-gut at 24 h p.i. and 72 h p.i. In conclusion, the results of this study suggest that MacroGard® stimulated CRP and complement responses to A. salmonicida infection in common carp. PMID:23291104

  8. Functional COMT Val158Met Polymorphism, Risk of Acute Coronary Events and Serum Homocysteine: The Kuopio Ischaemic Heart Disease Risk Factor Study

    PubMed Central

    Voutilainen, Sari; Tuomainen, Tomi-Pekka; Korhonen, Maarit; Mursu, Jaakko; Virtanen, Jyrki K.; Happonen, Pertti; Alfthan, Georg; Erlund, Iris; North, Kari E.; Mosher, M.J.; Kauhanen, Jussi; Tiihonen, Jari; Kaplan, George A.; Salonen, Jukka T.

    2007-01-01

    Background The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Methodology and Findings Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46–64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07–2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05–2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93–2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50–5.76) as compared with other men. Conclusions This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels. PMID:17264883

  9. CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure

    PubMed Central

    Stutchfield, Benjamin M.; Antoine, Daniel J.; Mackinnon, Alison C.; Gow, Deborah J.; Bain, Calum C.; Hawley, Catherine A.; Hughes, Michael J.; Francis, Benjamin; Wojtacha, Davina; Man, Tak Y.; Dear, James W.; Devey, Luke R.; Mowat, Alan M.; Pollard, Jeffrey W.; Park, B. Kevin; Jenkins, Stephen J.; Simpson, Kenneth J.; Hume, David A.; Wigmore, Stephen J.; Forbes, Stuart J.

    2015-01-01

    Background & Aims Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. Results Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. Conclusions Serum CSF1 appears to be a prognostic marker for patients

  10. Acute Phase Protein Lipocalin-2 Is Associated with Formalin-induced Nociception and Pathological Pain

    PubMed Central

    Jha, Mithilesh Kumar; Jeon, Sangmin; Jin, Myungwon; Lee, Won-Ha

    2013-01-01

    Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain. PMID:24385948

  11. Serum Potassium Levels Inversely Correlate with D-Dimer In Patients with Acute-Onset Atrial Fibrillation.

    PubMed

    Cervellin, Gianfranco; Bonfanti, Laura; Picanza, Alessandra; Lippi, Giuseppe

    2014-12-01

    Background: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared to subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. Objective: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared with subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. The aim of this study was to investigate correlations between D-dimer and serum potassium in acute-onset AF (AAF). Methods: To investigate the potential correlation between the values of serum potassium and D-dimer in patients with AAF, we retrospectively reviewed clinical and laboratory data of all emergency department visits for AAF in 2013. Results: Among 271 consecutive AAF patients with D-dimer assessments, those with hypokalemia (n = 98) had significantly higher D-dimer values than normokalemic patients (139 versus 114 ng/mL, p = 0.004). The rate of patients with D-dimer values exceeding the diagnostic cut-off was higher in the group of patients with hypokalemia than in those with normal serum potassium (26.5% versus 16.2%; p = 0.029). An inverse and highly significant correlation was found between serum potassium and D-dimer (r = -0.21; p < 0.001), even after adjustments for age and sex (beta coefficient -94.8; p = 0.001). The relative risk for a positive D-dimer value attributed to hypokalemia was 1.64 (95% CI, 1.02 to 2.63; p = 0.040). The correlation remained statistically significant in patients free from antihypertensive drugs (r = -0.25; p = 0.018), but not in those taking angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, or diuretics. Conclusions: The inverse correlation between values of potassium and D-dimer in patients with AAF provides important and complementary information about the thromboembolic risk of these patients.Fundamento: Valores de

  12. Serum-resistant CpG-STAT3 decoy for targeting survival and immune checkpoint signaling in acute myeloid leukemia

    PubMed Central

    Zhang, Qifang; Hossain, Dewan Md Sakib; Duttagupta, Priyanka; Moreira, Dayson; Zhao, Xingli; Won, Haejung; Buettner, Ralf; Nechaev, Sergey; Majka, Marcin; Zhang, Bin; Cai, Qi; Swiderski, Piotr; Kuo, Ya-Huei; Forman, Stephen; Marcucci, Guido

    2016-01-01

    Targeting oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) in acute myeloid leukemia (AML) can reduce blast survival and tumor immune evasion. Decoy oligodeoxynucleotides (dODNs), which comprise STAT3-specific DNA sequences are competitive inhibition of STAT3 transcriptional activity. To deliver STAT3dODN specifically to myeloid cells, we linked STAT3dODN to the Toll-like receptor 9 (TLR9) ligand, cytosine guanine dinucleotide (CpG). The CpG-STAT3dODN conjugates are quickly internalized by human and mouse TLR9+ immune cells (dendritic cells, B cells) and the majority of patients’ derived AML blasts, including leukemia stem/progenitor cells. Following uptake, CpG-STAT3dODNs are released from endosomes, and bind and sequester cytoplasmic STAT3, thereby inhibiting downstream gene expression in target cells. STAT3 inhibition in patients’ AML cells limits their immunosuppressive potential by reduced arginase expression, thereby partly restoring T-cell proliferation. Partly chemically modified CpG-STAT3dODNs have >60 hours serum half-life which allows for IV administration to leukemia-bearing mice (50% effective dose ∼ 2.5 mg/kg). Repeated administration of CpG-STAT3dODN resulted in regression of human MV4-11 AML in mice. The antitumor efficacy of this strategy is further enhanced in immunocompetent mice by combining direct leukemia-specific cytotoxicity with immunogenic effects of STAT3 blocking/TLR9 triggering. CpG-STAT3dODN effectively reduced Cbfb/MYH11/Mpl AML burden in various organs and eliminated leukemia stem/progenitor cells, mainly through CD8/CD4 T-cell–mediated immune responses. In contrast, small-molecule Janus kinase 2/STAT3 inhibitor failed to reproduce therapeutic effects of cell-selective CpG-STAT3dODN strategy. These results demonstrate therapeutic potential of CpG-STAT3dODN inhibitors with broad implications for treatement of AML and potentially other hematologic malignancies. PMID:26796361

  13. Serum-resistant CpG-STAT3 decoy for targeting survival and immune checkpoint signaling in acute myeloid leukemia.

    PubMed

    Zhang, Qifang; Hossain, Dewan Md Sakib; Duttagupta, Priyanka; Moreira, Dayson; Zhao, Xingli; Won, Haejung; Buettner, Ralf; Nechaev, Sergey; Majka, Marcin; Zhang, Bin; Cai, Qi; Swiderski, Piotr; Kuo, Ya-Huei; Forman, Stephen; Marcucci, Guido; Kortylewski, Marcin

    2016-03-31

    Targeting oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) in acute myeloid leukemia (AML) can reduce blast survival and tumor immune evasion. Decoy oligodeoxynucleotides (dODNs), which comprise STAT3-specific DNA sequences are competitive inhibition of STAT3 transcriptional activity. To deliver STAT3dODN specifically to myeloid cells, we linked STAT3dODN to the Toll-like receptor 9 (TLR9) ligand, cytosine guanine dinucleotide (CpG). The CpG-STAT3dODN conjugates are quickly internalized by human and mouse TLR9(+)immune cells (dendritic cells, B cells) and the majority of patients' derived AML blasts, including leukemia stem/progenitor cells. Following uptake, CpG-STAT3dODNs are released from endosomes, and bind and sequester cytoplasmic STAT3, thereby inhibiting downstream gene expression in target cells. STAT3 inhibition in patients' AML cells limits their immunosuppressive potential by reduced arginase expression, thereby partly restoring T-cell proliferation. Partly chemically modified CpG-STAT3dODNs have >60 hours serum half-life which allows for IV administration to leukemia-bearing mice (50% effective dose ∼ 2.5 mg/kg). Repeated administration of CpG-STAT3dODN resulted in regression of human MV4-11 AML in mice. The antitumor efficacy of this strategy is further enhanced in immunocompetent mice by combining direct leukemia-specific cytotoxicity with immunogenic effects of STAT3 blocking/TLR9 triggering. CpG-STAT3dODN effectively reducedCbfb/MYH11/MplAML burden in various organs and eliminated leukemia stem/progenitor cells, mainly through CD8/CD4 T-cell-mediated immune responses. In contrast, small-molecule Janus kinase 2/STAT3 inhibitor failed to reproduce therapeutic effects of cell-selective CpG-STAT3dODN strategy. These results demonstrate therapeutic potential of CpG-STAT3dODN inhibitors with broad implications for treatement of AML and potentially other hematologic malignancies. PMID:26796361

  14. The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia

    PubMed Central

    Cuartero, María Isabel; de la Parra, Juan; García-Culebras, Alicia; Ballesteros, Iván; Lizasoain, Ignacio; Moro, María Ángeles

    2016-01-01

    Kynurenines are a wide range of catabolites which derive from tryptophan through the “Kynurenine Pathway” (KP). In addition to its peripheral role, increasing evidence shows a role of the KP in the central nervous system (CNS), mediating both physiological and pathological functions. Indeed, an imbalance in this route has been associated with several neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. Altered KP catabolism has also been described during both acute and chronic phases of stroke; however the contribution of the KP to the pathophysiology of acute ischemic damage and of post-stroke disorders during the chronic phase including depression and vascular dementia, and the exact mechanisms implicated in the regulation of the KP after stroke are not well established yet. A better understanding of the regulation and activity of the KP after stroke could provide new pharmacological tools in both acute and chronic phases of stroke. In this review, we will make an overview of CNS modulation by the KP. We will detail the KP contribution in the ischemic damage, how the unbalance of the KP might trigger an alteration of the cognitive function after stroke as well as potential targets for the development of new drugs. PMID:25248805

  15. Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians

    PubMed Central

    Markanday, Anurag

    2015-01-01

    Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein have traditionally been used as markers for inflammation and as a measure of “sickness index” in infectious and noninfectious conditions. In the last decade, more data have become available on the wider and more specific role for these markers in the management of complex infections. This includes the potential role in early diagnosis, in differentiating infectious from noninfectious causes, as a prognostic marker, and in antibiotic guidance strategies. A better defined role for biological markers as a supplement to clinical assessment may lead to more judicious antibiotic prescriptions, and it has the potential for a long-term favorable impact on antimicrobial stewardship and antibiotic resistance. Procalcitonin as a biological marker has been of particular interest in this regard. This review examines the current published evidence and summarizes the role of various acute-phase markers in infections. A MEDLINE search of English-language articles on acute-phase reactants and infections published between 1986 and March 2015 was conducted. Additional articles were also identified through a search of references from the retrieved articles, published guidelines, systematic reviews, and meta-analyses. PMID:26258155

  16. Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

    PubMed

    Rodríguez-Angulo, H; Thomas, L E; Castillo, E; Cárdenas, E; Mogollón, F; Mijares, A

    2013-08-01

    Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase. PMID:23684908

  17. Determination of trapidil in human serum and urine by derivative UV spectrophotometry after selective solid-phase extraction.

    PubMed

    Ragno, Gaetano; Risoli, Antonella; De Luca, Michele; Ioele, Giuseppina; Oliverio, Filomena

    2007-10-01

    A novel analytical technique able to determine the anti-ischemic drug trapidil in human serum and urine is proposed. In order to achieve satisfactory sensitivity and selectivity, an extraction procedure was required to isolate the drug from complex matrixes such as serum and urine. A solid-phase extraction procedure was investigated to both increase the analyte concentration and eliminate the interfering molecules present in large amounts in both matrixes. Optimization of the extraction step was realized by selecting a new polymeric sorbent based on a surface-modified styrene-divinylbenzene polymer which provided fast and efficient drug extraction. Drug quantification was performed by using the third-order derivative spectra of the SPE eluates. Absorbance specific signals at (3)D(335,316) and (3)D(316) nm for urine and serum, respectively, were demonstrated to be directly proportional to drug concentration and barely affected by residual matrix interferences. Under the optimized experimental conditions the calibration plots were linear over the concentration range 0.2-50 microg mL(-1). The method was validated by analysis of a series of spiked samples. Accuracy (recovery of 95 and 94% for serum and urine, respectively) and precision (RSD below 4%) were good. PMID:17676316

  18. The Acute-Phase Protein Orosomucoid Regulates Food Intake and Energy Homeostasis via Leptin Receptor Signaling Pathway.

    PubMed

    Sun, Yang; Yang, Yili; Qin, Zhen; Cai, Jinya; Guo, Xiuming; Tang, Yun; Wan, Jingjing; Su, Ding-Feng; Liu, Xia

    2016-06-01

    The acute-phase protein orosomucoid (ORM) exhibits a variety of activities in vitro and in vivo, notably modulation of immunity and transportation of drugs. We found in this study that mice lacking ORM1 displayed aberrant energy homeostasis characterized by increased body weight and fat mass. Further investigation found that ORM, predominantly ORM1, is significantly elevated in sera, liver, and adipose tissues from the mice with high-fat diet (HFD)-induced obesity and db/db mice that develop obesity spontaneously due to mutation in the leptin receptor (LepR). Intravenous or intraperitoneal administration of exogenous ORM decreased food intake in C57BL/6, HFD, and leptin-deficient ob/ob mice, which was absent in db/db mice and was significantly reduced in mice with arcuate nucleus (ARC) LepR knockdown, whereas enforced expression of ORM1 in ARC significantly decreased food intake, body weight, and serum insulin level. Furthermore, we found that ORM is able to bind directly to LepR and activate the receptor-mediated JAK2-STAT3 signaling in hypothalamus tissue and GT1-7 cells, which was derived from hypothalamic tumor. These data indicated that ORM could function through LepR to regulate food intake and energy homeostasis in response to nutrition status. Modulating the expression of ORM is a novel strategy for the management of obesity and related metabolic disorders. PMID:27207522

  19. Pharmacokinetics of azithromycin in serum and sinus fluid after administration of extended-release and immediate-release formulations in patients with acute bacterial sinusitis.

    PubMed

    Ehnhage, A; Rautiainen, M; Fang, A F; Sanchez, S P

    2008-06-01

    As high drug levels at the infection site are desirable for optimal activity, this study explored whether one dose of azithromycin extended release (AZ-ER) achieved higher azithromycin exposure in sinus fluid than azithromycin immediate release (AZ-IR) in adults with acute bacterial sinusitis. Subjects received AZ-ER (2g single dose; n=5) or AZ-IR (500mg daily for 3 days; n=4) and blood and sinus aspirates were collected until 120 h after initial dosing. Within 24 h, exposure was four- and three-fold higher with AZ-ER than with AZ-IR in serum and sinus fluid, respectively. Sinus fluid exposure was five- and three-fold higher than serum for AZ-IR and AZ-ER, respectively. Azithromycin concentrations in sinus fluid were maintained up to 120 h. PMID:18456465

  20. Exploring the Relationship Between Serum and Urinary Free Light Chain Levels During the Different Phases of Renal Damage in Multiple Myeloma Patients.

    PubMed

    Xu, Zheng Li; Wu, Chao; Teng, Wen-Hao; Wan, Kai; Jia, Wei Jing; Li, Hui Jun; Meng, Li; Zhou, Jian Feng; Tang, Yi

    2015-09-01

    The objective was to explore the relationship between the levels of serum and urinary free light chains (FLCs) during the progression of renal damage in multiple myeloma (MM) patients. We examined 91 cases of MM patients, detected levels of serum FLCs (sFLCs), urinary FLCs (uFLCs), and serum creatinine at the same time, and then compared sFLC and uFLC levels during normal and abnormal serum creatinine phases. Among the 91 MM patients, 22 patients had abnormal serum creatinine levels (no uremia), and 69 patients had normal serum creatinine levels. The levels of sFLCs and uFLCs in patients with abnormal serum creatinine were beyond normal, namely both serum and urine positive (serum+ and urine+), and the average concentrations of κFLCs and λFLCs were 516.76 and 604.67 mg/L, respectively. Of the 69 patients with normal creatinine levels, there were 39 and 30 cases of κ-type and λ-type MM, respectively. Of the κ-type patients, 11 cases were serum positive and urine negative (serum+ and urine-) with an average concentration of 55.47 mg/L, and 28 cases were serum positive and urine positive (serum+ and urine+) with an average concentration of 513.09 mg/L. Of the λ-type patients, 16 cases were serum positive and urine negative (serum+ and urine-) with an average concentration of 78.44 mg/L, and 14 cases were serum positive and urine positive (serum+ and urine+) with an average concentration of 518.08 mg/L. The levels of uFLCs did not parallel those of sFLCs. In addition to sFLC levels, renal function affected uFLC concentrations. As MM progressed, the concentration of sFLCs increased in a step-by-step manner, and the uFLCs changed from negative to positive to negative again. Therefore, the whole progression included three phases: sserum+ and urine-, serum+ and urine+, and then serum+ and urine-. PMID:26085720

  1. The concentrations of inflammatory cytokines and acute-phase proteins in the peripheral blood and uterine washings in cows with pyometra.

    PubMed

    Brodzki, P; Kostro, K; Brodzki, A; Ziętek, J

    2015-06-01

    The development of pyometra in cows depends largely on the state of local immunity of the uterus. The objective of the study was to evaluate the concentration of the following proinflammatory cytokines: tumour necrosis factor (TNF-α) and interleukin-6 (IL-6); anti-inflammatory cytokine: interleukin-10 (IL-10); and acute-phase proteins (APPs): haptoglobin (Hp) and serum amyloid A (SAA), in serum and uterine washings in cows with pyometra and healthy animals. The study was performed on 20 cows divided into two groups based on the results of cytological and ultrasonographic tests: a pyometra and a healthy group (10 cows per group). Experimental material consisted of blood serum and uterine washings. The levels of the following cytokines, TNF-α, IL-6, IL-10 and APPs - Hp and SAA, in the study material were determined by ELISA. The results showed that the values of TNF-α, IL-6, IL-10 as well as SAA and Hp were significantly higher in serum of cows with pyometra compared to controls (p < 0.001). The uterine washings had significantly higher levels of IL-6, IL-10, and Hp in pyometra cows compared to the control (p < 0.001). Our results indicate that it is possible to monitor the course of pyometra in cows based on the evaluation of the concentration of cytokines and Hp in the serum and uterine washings. Simultaneous evaluation of selected indicators of antagonistic interaction can be helpful in determining the current status of local immunity of the uterus. On this basis, it could be possible to properly select an adjunctive therapy in the form of immunomodulating preparations. PMID:25704413

  2. Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis

    PubMed Central

    Oguri, Masayoshi; Saito, Yoshiaki; Fukuda, Chisako; Kishi, Kazuko; Yokoyama, Atsushi; Lee, Sooyoung; Torisu, Hiroyuki; Toyoshima, Mitsuo; Sejima, Hitoshi; Kaji, Shunsaku; Hamano, Shin-ichiro; Okanishi, Toru; Tomita, Yutaka; Maegaki, Yoshihiro

    2016-01-01

    Background To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. Methods We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. Results Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. Conclusion Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD. PMID:27046946

  3. A sericin-derived peptide protects sf9 insect cells from death caused by acute serum deprivation.

    PubMed

    Takahashi, Masakazu; Tsujimoto, Kazuhisa; Kato, Youichi; Yamada, Hideyuki; Takagi, Hiroshi; Nakamori, Shigeru

    2005-07-01

    Sericin is the silk protein enveloping fibroin fibers in cocoons. Sericin hydrolysate protects cultured Sf9 insect cells from death caused by serum deprivation; the activity depends on the repeats of 38 amino acids. A partial peptide from the 38 residues, SGGSSTYGYS, inhibited serum-deprivation death as well. Cell viabilities in the presence of 10% (v/v) foetal calf serum, no additives and 1 mM: SGGSSTYGYS were 96, 12 and 31% on the third day after inoculation, respectively. Aromatic residues seemed to be important because SGGSSTWGWS had the same activity as SGGSSTYGYS but SGGSSTAGAS had no activity. PMID:16091882

  4. Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy☆

    PubMed Central

    de Macêdo, Thalita Medeiros Fernandes; Campos, Tania Fernandes; Mendes, Raquel Emanuele de França; França, Danielle Corrêa; Chaves, Gabriela Suéllen da Silva; de Mendonça, Karla Morganna Pereira Pinto

    2014-01-01

    OBJECTIVE: The aim of this study was to assess the pulmonary function of children with acute leukemia. METHODS: Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(r) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(r)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. RESULTS: Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. CONCLUSION: Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength. PMID:25510995

  5. Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury.

    PubMed

    Thakore, Nakul P; Samantaray, Supriti; Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Cox, April; Krause, James; Banik, Naren L

    2016-02-01

    To clarify the molecular changes of sublesional muscle in the acute phase of spinal cord injury (SCI), a moderately severe injury (40 g cm) was induced in the spinal cord (T10 vertebral level) of adult male Sprague-Dawley rats (injury) and compared with sham (laminectomy only). Rats were sacrificed at 48 h (acute) post injury, and gastrocnemius muscles were excised. Morphological examination revealed no significant changes in the muscle fiber diameter between the sham and injury rats. Western blot analyses performed on the visibly red, central portion of the gastrocnemius muscle showed significantly higher expression of muscle specific E3 ubiquitin ligases (muscle ring finger-1 and muscle atrophy f-box) and significantly lower expression of phosphorylated Akt-1/2/3 in the injury group compared to the sham group. Cyclooxygenase 2, tumor necrosis factor alpha (TNF-α), and caspase-1, also had a significantly higher expression in the injury group; although, the mRNA levels of TNF-α and IL-6 did not show any significant difference between the sham and injury groups. These results suggest activation of protein degradation, deactivation of protein synthesis, and development of inflammatory reaction occurring in the sublesional muscles in the acute phase of SCI before overt muscle atrophy is seen. PMID:26290268

  6. Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction

    SciTech Connect

    Suzuki, A.; Matsushima, H.; Satoh, A.; Hayashi, H.; Sotobata, I.

    1988-06-01

    A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

  8. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

    PubMed Central

    Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

    2016-01-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

  9. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever.

    PubMed

    Cui, Liang; Lee, Yie Hou; Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R

    2016-04-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism-serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

  10. An accurate two-phase approximate solution to the acute viral infection model

    SciTech Connect

    Perelson, Alan S

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  11. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    SciTech Connect

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  12. Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection Following Adult Liver Transplantation

    PubMed Central

    Kim, Nayoung; Yoon, Young-In; Yoo, Hyun Ju; Tak, Eunyoung; Ahn, Chul-Soo; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin

    2016-01-01

    Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity. PMID:27498551

  13. [THE EFFECT OF ACTH-(4-7)-PGP PEPTIDE ON LIPID PEROXIDATION IN LIVER AND ACTIVITY OF SERUM TRANSAMINASES IN RATS UNDER ACUTE AND CHRONIC IMMOBILIZATION STRESS CONDITIONS].

    PubMed

    Bobyntsev, I; Kryukov, A A; Shepeleva, M; Ivanov, A V

    2015-01-01

    The effect of ACTH-(4-7)-PGP (semax) intraperitoneal injection at doses of 5, 50, 150 and 450 μg/kg b.w. on the free-radical oxidation and the activity of serum transaminases in Wistar male rats subjected to acute and chronic immobilization stress has been studied. It was found that the peptide administration in the entire dose range studied produced antioxidant effect in hepatocytes and significantly increased the activity of serum ALT and AST at a dose of 450 μg/kg under chronic stress conditions. On the contrary, prooxidant effects were observed at a drug dose of 150 mg/kg under acute stress conditions, and the direction of changes in the ALT and AST values activity depended on the semax dose. The ALT activity was decreased at doses of 5 and 50 μg/kg, but increased at a dose of 450 μg/kg. The AST activity was already reliably increased at a dose of 5 μg/kg. PMID:26591577

  14. Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

    Acute Myeloid Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following; Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  15. Scintigraphic evaluation of digital circulation during the developmental and acute phases of equine laminitis

    SciTech Connect

    Trout, D.R.

    1987-01-01

    Using nuclear isotopic imaging, digital circulation was sequentially evaluated at 24-hour intervals in 11 control horses and in 9 horses affected with acute laminitis, created by administration of a high-starch ration. Following intra-arterial injection of /sup 99m/Tc macroaggregated albumin into the brachiocephalic trunk, a gamma camera and dedicated nuclear medicine computer were used to acquire static images of the right front foot. Dynamic vascular-phase and static interstitial-phase images were also obtained after jugular vein injection of /sup 99m/Tc diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquilization. The images were quantitatively analyzed for parameters indicative of circulation to the foot as a whole and to specific regions of interest within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Although total flow tended to increase throughout the peripheral/external regions of the foot, statistically significant elevations were consistently present only within the lamellae. Changes indicative of decreased total blood flow were noted in the central/internal regions of the foot. These alterations usually occurred coincident with or after the onset of clinical lameness.

  16. Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans.

    PubMed

    Schwab, Ursula; Törrönen, Anneli; Meririnne, Esa; Saarinen, Markku; Alfthan, Georg; Aro, Antti; Uusitupa, Matti

    2006-01-01

    Betaine, i.e., trimethylglycine, is linked to homocysteine metabolism. A 3-mo daily betaine supplementation decreased even normal plasma total homocysteine (tHcy) concentrations in humans. The pharmacokinetic characteristics and metabolism of betaine in humans have not been investigated in detail. The aim of this study was to assess the pharmacokinetics of orally administered betaine and its acute effect on plasma tHcy concentrations. Healthy volunteers (n = 10; 3 men, 7 women) with normal body weight (mean +/- SD, 69.5 +/- 17.0 kg), 40.8 +/- 12.4 y old, participated in the study. The betaine doses were 1, 3, and 6 g. The doses were mixed with 150 mL of orange juice and ingested after a 12-h overnight fast by each volunteer according to a randomized double-blind crossover design. Blood samples were drawn for 24 h and a 24-h urine collection was performed. Orally administered betaine had an immediate and dose-dependent effect on serum betaine concentration. Single doses of 3 and 6 g lowered plasma tHcy concentrations (P = 0.019 and P < 0.001, respectively), unlike the 1-g dose. After the highest dose, the concentrations remained low during the 24 h of monitoring. The change in plasma tHcy concentration was linearly associated with betaine dose (P = 0.006) and serum betaine concentration (R2 = 0.17, P = 0.025). The absorption and elimination of betaine were dose dependent. The urinary excretion of betaine seemed to increase with an increasing betaine dose, although a very small proportion of ingested betaine was excreted via urine. In conclusion, a single dose of orally administered betaine had an acute and dose-dependent effect on serum betaine concentration and resulted in lowered plasma tHcy concentrations within 2 h in healthy subjects. PMID:16365055

  17. Serum microRNA181a: Correlates with the intracellular cytokine levels and a potential biomarker for acute graft-versus-host disease.

    PubMed

    Xie, Linna; Zhou, Fang; Liu, Ximin; Fang, Yuan; Yu, Zhe; Song, Ningxia; Kong, Fansheng

    2016-09-01

    The aim of this study was to investigate the clinical relevance of lymphocyte-related serum miRNAs to the pathogenesis of acute graft-versus-host disease (aGVHD) and evaluate the predictive and prognosis value of miRNAs. Consecutive patients who received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in General Hospital of Jinan Military District were enrolled. aGVHD patients were diagnosed and graded clinically, and divided into the training set and the testing set. Blood samples were collected, total RNA was isolated, and RT-PCR was performed for miRNA expression (miR-181a-3p, miR-214-3p and miR-326). Intracellular cytokines levels were assayed by flow cytometry, and the disease specificity assay of miRNAs for aGVHD was detected. A total of 120 patients were admitted. Serum level of miR-181a in aGVHD patients was highly increased and associated with the severity of aGVHD, but not miR-214 and miR-326. Levels of cytokines including IL-2, IL-22, and IL-17a were positively correlated with miR-181a level, while serum IL-13 level was negatively correlated with miR-181a level in aGVHD patients. Moreover, increased miR-181a level was not detected in patients with acute rejection after kidney transplantation or sepsis patients. MiR-181a level was sensitively and specifically increased, especially in severe aGVHD patients. MiR-181a may be a potential biomarker for the identification, diagnosis, and prognosis of aGVHD patients. PMID:27288630

  18. Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

    PubMed Central

    Förster, Alex; Al-Zghloul, Mansour; Kerl, Hans U.; Böhme, Johannes; Mürle, Bettina; Groden, Christoph

    2015-01-01

    Purpose Transient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase. Methods From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL). Results Five TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus. Conclusions Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in

  19. Serum Fatty Acids, Traditional Risk Factors, and Comorbidity as Related to Myocardial Injury in an Elderly Population with Acute Myocardial Infarction

    PubMed Central

    Seljeflot, Ingebjørg; Schmidt, Erik B.; Myhre, Peder; Tveit, Arnljot; Arnesen, Harald

    2016-01-01

    Background. Epidemiological and randomized clinical trials indicate that marine polyunsaturated n-3 fatty acids (n-3 PUFAs) may have cardioprotective effects. Aim. Evaluate the associations between serum fatty acid profile, traditional risk factors, the presence of cardiovascular diseases (CVD), and peak Troponin T (TnT) levels in elderly patients with an acute myocardial infarction (AMI). Materials and Methods. Patients (n = 299) consecutively included in the ongoing Omega-3 fatty acids in elderly patients with myocardial infarction (OMEMI) trial were investigated. Peak TnT was registered during the hospital stay. Serum fatty acid analysis was performed 2–8 weeks later. Results. No significant correlations between peak TnT levels and any of the n-3 PUFAs were observed. However, patients with a history of atrial fibrillation had significantly lower docosahexaenoic acid levels than patients without. Significantly lower peak TnT levels were observed in patients with a history of hyperlipidemia, angina, MI, atrial fibrillation, intermittent claudication, and previous revascularization (all p < 0.02). Conclusions. In an elderly population with AMI, no association between individual serum fatty acids and estimated myocardial infarct size could be demonstrated. However, a history of hyperlipidemia and the presence of CVD were associated with lower peak TnT levels, possibly because of treatment with cardioprotective medications. PMID:26989512

  20. Serum Fatty Acids, Traditional Risk Factors, and Comorbidity as Related to Myocardial Injury in an Elderly Population with Acute Myocardial Infarction.

    PubMed

    Laake, Kristian; Seljeflot, Ingebjørg; Schmidt, Erik B; Myhre, Peder; Tveit, Arnljot; Arnesen, Harald; Solheim, Svein

    2016-01-01

    Background. Epidemiological and randomized clinical trials indicate that marine polyunsaturated n-3 fatty acids (n-3 PUFAs) may have cardioprotective effects. Aim. Evaluate the associations between serum fatty acid profile, traditional risk factors, the presence of cardiovascular diseases (CVD), and peak Troponin T (TnT) levels in elderly patients with an acute myocardial infarction (AMI). Materials and Methods. Patients (n = 299) consecutively included in the ongoing Omega-3 fatty acids in elderly patients with myocardial infarction (OMEMI) trial were investigated. Peak TnT was registered during the hospital stay. Serum fatty acid analysis was performed 2-8 weeks later. Results. No significant correlations between peak TnT levels and any of the n-3 PUFAs were observed. However, patients with a history of atrial fibrillation had significantly lower docosahexaenoic acid levels than patients without. Significantly lower peak TnT levels were observed in patients with a history of hyperlipidemia, angina, MI, atrial fibrillation, intermittent claudication, and previous revascularization (all p < 0.02). Conclusions. In an elderly population with AMI, no association between individual serum fatty acids and estimated myocardial infarct size could be demonstrated. However, a history of hyperlipidemia and the presence of CVD were associated with lower peak TnT levels, possibly because of treatment with cardioprotective medications. PMID:26989512

  1. [Fibrinogen--acute phase protein as a marker of immunological process as atherosclerosis].

    PubMed

    Rajtari, Renata; Kloch, Małgorzata; Kiec-Wilk, Beata; Kolasińska-Kloch, Władysława

    2005-01-01

    The most important CAD risk factors are: smoking, high level of LDL-cholesterol and low level of HDL-cholesterol, hypertriglyceridemia, diabetes, obesity, hypertension, men sex, age over 45 in men and over 55 in women. Carl von Rokitański was the first who suggested the role of thrombosis and fibrynolisis in the development of atherosclerosis and was the author of thrombolic theory. The recently studies show that atherosclerosis is an immuno-inflamatory process. Fibrinogen as an acute phase protein is a new marker of ischemic heart disease and its role in atherosclerosis needs further investigations. PMID:17037285

  2. Identification of an acute-phase reactant in murine infections with Trypanosoma brucei.

    PubMed Central

    Shapiro, S Z; Black, S J

    1992-01-01

    A 42-kDa protein appeared at a much higher concentration in plasma from Trypanosoma brucei-resistant (C57BL/6) mice after infection than in plasma from trypanosome-susceptible (C3H/He) mice. This protein was purified by sequential steps of gel filtration, protein A-Sepharose affinity chromatography, isoelectric focusing, and ammonium sulfate precipitation. The purified protein was identified as a subunit of the acute-phase reactant haptoglobin. Causes of elevated plasma haptoglobin and its implications for resistance to trypanosomiasis are discussed. Images PMID:1500201

  3. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures.

    PubMed Central

    Van Lenten, B J; Hama, S Y; de Beer, F C; Stafforini, D M; McIntyre, T M; Prescott, S M; La Du, B N; Fogelman, A M; Navab, M

    1995-01-01

    We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule. Images PMID:8675645

  4. Acute phase response to Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum' infection in FIV-infected and non-FIV-infected cats.

    PubMed

    Korman, R M; Cerón, J J; Knowles, T G; Barker, E N; Eckersall, P D; Tasker, S

    2012-08-01

    The pathogenicity of Haemoplasma spp. in cats varies with 'Candidatus Mycoplasma haemominutum' (CMhm) causing subclinical infection while Mycoplasma haemofelis (Mhf) often induces haemolytic anaemia. The aims of this study were to characterise the acute phase response (APR) of the cat to experimental infection with Mhf or CMhm, and to determine whether chronic feline immunodeficiency virus (FIV) infection influences this response. The acute phase proteins serum amyloid A (SAA), haptoglobin (Hp) and α-1-acid glycoprotein (AGP) concentrations were measured pre-infection and every 7-14 days up to day 100 post-infection (pi) in cats infected with either Mhf or CMhm. Half of each group of cats (6/12) were chronically and subclinically infected with FIV. Marbofloxacin treatment was given on days 16-44 pi to half of the Mhf-infected cats, and on days 49-77 pi to half of the CMhm-infected cats. FIV-infected animals had significantly lower AGP concentrations, and significantly greater Hp concentrations than non-FIV-infected cats when infected with CMhm and Mhf, respectively. Both CMhm and Mhf infection were associated with significant increases in SAA concentrations, while AGP concentrations were only significantly increased by Mhf infection. Mhf-infected cats had significantly greater SAA concentrations than CMhm-infected animals. Both Mhf and CMhm infections were associated with an APR, with Mhf infection inducing a greater response. Chronic FIV infection appeared to modify the APR, which varied with the infecting Haemoplasma species. PMID:22763129

  5. Electrolyte effect on the phase behavior of silica nanoparticles with lysozyme and bovine-serum-albumin proteins

    NASA Astrophysics Data System (ADS)

    Yadav, Indresh; Aswal, V. K.; Kohlbrecher, J.

    2015-05-01

    Small-angle neutron scattering (SANS) and dynamic light scattering (DLS) studies have been carried out to investigate the effect of an electrolyte on the phase behavior of anionic silica nanoparticles with two globular proteins—cationic lysozyme [molecular weight (MW) 14.7 kDa] and anionic bovine serum albumin (MW 66.4 kDa). The results are compared with our earlier published work on similar systems without any electrolyte [I. Yadav, S. Kumar, V. K. Aswal, and J. Kohlbrecher, Phys. Rev. E 89, 032304 (2014), 10.1103/PhysRevE.89.032304]. Both the nanoparticle-protein systems transform to two phase at lower concentration of protein in the presence of an electrolyte. The autocorrelation function in DLS suggests that the diffusion coefficient (D) of a nanoparticle-protein system decreases in approaching two phase with the increase in protein concentration. This variation in D can be attributed to increase in attractive interaction and/or overall increase in the size. Further, these two contributions (interaction and structure) are determined from the SANS data. The changes in the phase behavior of nanoparticle-protein systems in the presence of an electrolyte are explained in terms of modifications in both the repulsive and attractive components of interaction between nanoparticles. In a two-phase system individual silica nanoparticles coexist along with their fractal aggregates.

  6. Inflammatory cytokines and acute-phase proteins concentrations in the peripheral blood and uterus of cows that developed endometritis during early postpartum.

    PubMed

    Brodzki, P; Kostro, K; Brodzki, A; Wawron, W; Marczuk, J; Kurek, Ł

    2015-07-01

    The aim of the study was to evaluate the level of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]), anti-inflammatory cytokine (interleukin-10 [IL-10]), and acute-phase proteins (haptoglobin [Hp] and serum amyloid A [SAA]) in serum and uterine washings in cows that developed endometritis during the early postpartum period. The study was carried out on 40 cows. The experimental group consisted of 20 cows with subclinical endometritis and the control group of 20 cows without endometritis. Analyses in both groups of cows were carried out at 5, 22, and 40 days postpartum (DPP). Experimental material consisted of the blood serum and uterine washings. The levels of the following cytokines: TNF-α, IL-6, IL-10 and acute-phase proteins: Hp and SAA were determined using ELISA. Our study reported that the levels of TNF-α, IL-6, IL-10, Hp, and SAA at 22 DPP were higher in cows with subclinical endometritis (P < 0.001). The levels of TNF-α (P = 0.01), IL-6 and IL-10 (P = 0.001), and Hp (P < 0.001) at 40 DPP were higher in cows with subclinical endometritis compared to healthy cows. The level of IL-10 in uterine washings at 5 DPP was higher (P = 0.001), whereas of SAA was lower (P = 0.01) in cows with subclinical endometritis. At 22 DPP, the levels of IL-6, IL-10, and Hp were higher (P < 0.001) in cows with endometritis. At 40 DPP, the level of TNF-α was lower, whereas these of IL-10 and Hp were elevated (P < 0.001) in cows with endometritis compared to healthy cows. The results indicate that the evaluation of the levels of cytokines and Hp in serum, but primarily in uterine washings, can be an important diagnostic indicator in cows that developed subclinical endometritis. High levels of IL-10 in cows with subclinical endometritis may contribute to the weakening of local resistance mechanisms of the uterus and lead to the persistence of the inflammation in the postpartum period. The present study also shows that the simultaneous examination

  7. Feeding common carp Cyprinus carpio with β-glucan supplemented diet stimulates C-reactive protein and complement immune acute phase responses following PAMPs injection.

    PubMed

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna J; Shrive, Annette K; Hoole, Dave

    2014-08-01

    The effect of β-glucan as a feed additive on the serum and gene profile of C-reactive protein (CRP) and complement acute phase responses was ascertained in common carp Cyprinus carpio. In addition effects of subsequent intraperitoneal injections of pathogen-associated molecular patterns (PAMPs), i.e. LPS or poly(I:C), to mimic bacterial or viral infection respectively, were studied. Carp were first orally fed with β-glucan (MacroGard®) with a daily β-glucan intake of 6 mg per kg body weight or with control food for 25 days and then injected with PBS containing either LPS (4 mg/kg) or poly(I:C) (5 mg/kg) or PBS alone. Fish were sampled during the 25 days of the feeding period and up to 7 days post-PAMPs injections for serum and liver, head kidney and mid-gut tissues. Oral administration of β-glucan for 25 days significantly increased serum CRP levels and alternative complement activity (ACP). In addition, the subsequent LPS and poly(I:C) challenges significantly affected CRP and complement related gene expression profiles (crp1, crp2, c1r/s, bf/c2, c3 and masp2), with the greatest effects observed in the β-glucan fed fish. However, in fish fed β-glucan the PAMPs injections had less effects on CRP levels and complement activity in the serum than in control fed fish, suggesting that the 25 days of β-glucan immunostimulation was sufficient enough to reduce the effects of LPS and poly(I:C) injections. Results suggest that MacroGard® stimulated CRP and complement responses to PAMPs immunological challenges in common carp thus highlighting the beneficial β-glucan immunostimulant properties. PMID:24830773

  8. Challenges in detecting pre-malignant pancreatic lesions during acute pancreatitis using a serum microRNA assay: a study based on KrasG12D transgenic mice

    PubMed Central

    Hong, Xiafei; Zhang, Jie; Wu, Qiao; Wang, Wenze; Ye, Adam Yongxin; Song, Wei; Dai, Hongmei; Wang, Xianze; Wu, Fan; You, Lei; Wu, Wenming; Zhao, Yupei

    2016-01-01

    Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. Mechanistically, Gene Set Enrichment Analysis (GSEA) of the mRNA array data and immunohistochemical assays showed that caerulein-induced acute pancreatitis involved acinar cell loss and immune cell infiltration, which might contribute to serum miRNA profile changes. This study highlighted the challenges in using sensitive serum miRNA biomarker screening for the early detection of pancreatic malignancies during acute pancreatitis. PMID:27009811

  9. Cytokine kinetics of Zika virus-infected patients from acute to reconvalescent phase.

    PubMed

    Tappe, Dennis; Pérez-Girón, José Vicente; Zammarchi, Lorenzo; Rissland, Jürgen; Ferreira, Davis F; Jaenisch, Thomas; Gómez-Medina, Sergio; Günther, Stephan; Bartoloni, Alessandro; Muñoz-Fontela, César; Schmidt-Chanasit, Jonas

    2016-06-01

    Zika virus is an emerging mosquito-borne flavivirus currently causing large epidemics in the Pacific Ocean region and Brazil. Clinically, Zika fever resembles dengue fever, but is less severe. Whereas the clinical syndrome and laboratory diagnostic procedures have been described, little attention was paid to the immunology of the disease and its possible use for clinical follow-up of patients. Here, we investigate the role of cytokines in the pathogenesis of Zika fever in travelers returning from Asia, the Pacific, and Brazil. Polyfunctional T cell activation (Th1, Th2, Th9, and Th17 response) was seen during the acute phase characterized by respective cytokine level increases, followed by a decrease in the reconvalescent phase. PMID:26702627

  10. Evaluation of serum cysteine-rich protein 61 and cystatin C levels for assessment of acute kidney injury after cardiac surgery.

    PubMed

    Mosa, Osama F; Skitek, Milan; Kalisnik, Jurij M; Jerin, Ales

    2016-06-01

    Objective The occurrence of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) can lead to morbidity and mortality. We hypothesized that cysteine-rich protein 61 (CYR61) and cystatin C (CysC) may be potential novel biomarkers of AKI after cardiopulmonary bypass. Methods Patients were classified into AKI and non-AKI group depending on serum creatinine. Levels of creatinine, CysC, and CYR61 were measured at five time-points before and within 48 h after the surgery. Results Fifty patients were included in the study. Serum creatinine pre-operative values were 74.0 ± 43.3 μmol/L in AKI group vs. 64.8 ± 17.9 μmol/L in non-AKI group. During 48 h, the values increased to 124.6 ± 67.2 μmol/L in AKI group (p < 0.001) but in non-AKI group they did not change significantly. Serum CysC values were significantly increased already 2 h after CBP in AKI group (949 ± 557 μg/L, p < 0.05) compared to non-AKI group (700 ± 170 μg/L). Pre-operative serum CYR61 tended to be lower in AKI group (12.4 μg/L) than in non-AKI group (20.3 μg/L), but 24 h after the surgery, the levels in AKI group tended to be higher than non-AKI group. Conclusion Serum CYR61 does not seem to be an early predictor of AKI in patients after cardiac surgery with CPB, but it might possibly identify patients at risk of developing more severe kidney injury. Serum CysC could be a promising biomarker of AKI, differentiating patients at risk of developing AKI after cardiac surgery as early as 2 h after surgery. PMID:26982887

  11. Effectiveness of Acute Phase Hybrid Assistive Limb Rehabilitation in Stroke Patients Classified by Paralysis Severity

    PubMed Central

    FUKUDA, Hiroyuki; SAMURA, Kazuhiro; HAMADA, Omi; SAITA, Kazuya; OGATA, Toshiyasu; SHIOTA, Etsuji; SANKAI, Yoshiyuki; INOUE, Tooru

    The purpose of the present study was to investigate the effectiveness of acute phase hybrid assistive limb (HAL) rehabilitation training for patients after stroke by measuring the difference in the severity of paralysis. Fifty-three acute stroke patients were enrolled in this prospective cohort study. HAL training was administered about twice per week, and the mean number of sessions was 3.9 ± 2.7. The walking training was performed on a treadmill with individually adjustable body weight support and speed and there was a 10-m walk test (10MWT) before and after each session. Assessment at baseline and at endpoint consisted of the Glasgow Coma Scale (GCS), Revised Hasegawa’s Dementia Scale (HDS-R), Brunnstrom stage (Brs), Functional Independence Measure (FIM), Barthel index (BI), and 10MWT. We measured these assessments at the first walking training session and at the end of the final training session without the HAL. To evaluate the feasibility of training with the HAL, the outcome measures of BI, FIM, and speed and number of steps of 10MWT were compared before and after training using a paired Wilcoxon’s signed-rank test in different Brs. Except for Brs IV, the Brs III or higher subgroups displayed significant amelioration in BI, and the Brs III subgroup displayed significant amelioration in FIM. The Brs V and VI subgroups displayed significant amelioration in 10-m walking speed and steps. In acute phase rehabilitation after stroke, it is thought that the HAL is more effective for patients with less lower-limb paralysis, such as Brs III or higher. PMID:26041627

  12. T Helper Subsets, Peripheral Plasticity, and the Acute Phase Protein, α1-Antitrypsin

    PubMed Central

    Baranovski, Boris M.; Freixo-Lima, Gabriella S.; Lewis, Eli C.; Rider, Peleg

    2015-01-01

    The traditional model of T helper differentiation describes the naïve T cell as choosing one of several subsets upon stimulation and an added reciprocal inhibition aimed at maintaining the chosen subset. However, to date, evidence is mounting to support the presence of subset plasticity. This is, presumably, aimed at fine-tuning adaptive immune responses according to local signals. Reprograming of cell phenotype is made possible by changes in activation of master transcription factors, employing epigenetic modifications that preserve a flexible mode, permitting a shift between activation and silencing of genes. The acute phase response represents an example of peripheral changes that are critical in modulating T cell responses. α1-antitrypsin (AAT) belongs to the acute phase responses and has recently surfaced as a tolerogenic agent in the context of adaptive immune responses. Nonetheless, AAT does not inhibit T cell responses, nor does it shutdown inflammation per se; rather, it appears that AAT targets non-T cell immunocytes towards changing the cytokine environment of T cells, thus promoting a regulatory T cell profile. The present review focuses on this intriguing two-way communication between innate and adaptive entities, a crosstalk that holds important implications on potential therapies for a multitude of immune disorders. PMID:26583093

  13. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.

    PubMed

    Panis, Carolina; Pizzatti, Luciana; Bufalo, Aedra Carla; Herrera, Ana Cristina; Victorino, Vanessa Jacob; Cecchini, Rubens; Abdelhay, Eliana

    2016-03-01

    Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment. PMID:26472721

  14. Strategies for Early Non-response to Antipsychotic Drugs in the Treatment of Acute-phase Schizophrenia

    PubMed Central

    Ito, Hiroto

    2014-01-01

    As a strategy for antipsychotic treatment of schizophrenia, monotherapy is clearly optimal when both effective and tolerated. When a patient fails to respond to an adequate dose of an antipsychotic, alternatives include switching, administering a higher dose (above the licensed dose), polypharmacy or clozapine. Clozapine is the only option with established efficacy, but is less manageable than other antipsychotics. We therefore reviewed other options, focusing on the treatment of acute-phase schizophrenia. According to recent evidence, an antipsychotic may be viewed as ineffective within 1-4 weeks in acute-phase practice, although some differences may exist among antipsychotics. Whether a switching strategy is effective might depend on the initial antipsychotic and which antipsychotic is switched to. As weak evidence points toward augmentation being superior to continuation of the initial antipsychotic, inclusion of augmentation arms in larger studies comparing strategies for early non-responders in the acute-phase is justified. With respect to high-doses, little evidence is available regarding acute-phase treatment, and the issue remains controversial. Although evidence for antipsychotic switching, augmentation, and high-doses has gradually been accumulating, more studies performed in real clinical practice with minimal bias are required to establish strategies for early non-response to an antipsychotic drug in the treatment of acute-phase schizophrenia. PMID:24851115

  15. Sucrose dependence of solute retention on human serum albumin stationary phase: hydrophobic effect and surface tension considerations.

    PubMed

    Peyrin, E; Guillaume, Y C; Morin, N; Guinchard, C

    1998-07-15

    In a chromatographic system using human serum albumin (HSA) as a stationary phase, D,L dansyl amino acids as solutes, and sucrose as a mobile-phase modifier, a study on the surface tension effect of sugar on compound retention was carried out by varying the salting-out agent concentration c and the column temperature T. The thermodynamic parameters for solute transfer from the mobile to the stationary phase were determined from linear van't Hoff plots. An enthalpy-entropy compensation study revealed that the type of interaction between solute and HSA was independent of the molecular structure of the dansyl amino acids and the mobile-phase composition. An analysis of the experimental variations in the retention factor and the enantioselectivity values with c was performed using a theoretical model. It was shown that the decrease in solute retention accompanying the sucrose concentration increase was principally governed by a structural rearrangement of the binding cavity due to the increased surface tension effects. The cavity apolar residues were assumed to fold out of contact with the medium in order to reduce the surface area accessible to sucrose molecules, thus implying a restriction of the curvature radius of the cavity. Such behavior caused a decrease in the hydrophobic interaction for ligand binding on HSA explaining the observed thermodynamic parameter trends over the sucrose concentration range. PMID:9684542

  16. Joint aqueous solutions of dextran and bovine serum albumin: coexistence of three liquid phases.

    PubMed

    Antonov, Yurij; Wolf, Bernhard A

    2014-06-10

    The phase diagram of the system water/dextran (DEX)/BSA was measured as well as modeled. On the experimental side, cloud points were determined and the coexisting phases were analyzed. The theoretical calculations use an approach capable of describing solutions of chain polymers and of globular proteins with the same formalism. The required thermodynamic input comes from experiments concerning the binary subsystems, except for the polymer blend for which one interaction parameter had to be adjusted. Both sources of information yield the same essential features: the existence of a large composition area of immiscibility, starting from the subsystem DEX/BSA and extending well into the region of dilute polymer solutions. This range is subdivided into three sections: one two-phase area at high polymer content, a two-phase area at low polymer content, and a three-phase region located in between. Measured and calculated phase diagrams match qualitatively; the reasons for the quantitative discrepancies are being discussed. PMID:24832129

  17. Serum globulin electrophoresis

    MedlinePlus

    ... may indicate: Acute infection Bone marrow cancer called multiple myeloma Chronic inflammatory disease (for example, rheumatoid arthritis and ... test Hemoglobin Hyperimmunization Immunoelectrophoresis - ... electrophoresis - serum Rheumatoid arthritis Systemic lupus erythematosus ...

  18. Acute Lonomia obliqua caterpillar envenomation-induced physiopathological alterations in rats: evidence of new toxic venom activities and the efficacy of serum therapy to counteract systemic tissue damage.

    PubMed

    Berger, Markus; Beys-da-Silva, Walter Orlando; Santi, Lucélia; de Oliveira, Iuri Marques; Jorge, Patrícia Mendes; Henriques, João Antônio Pêgas; Driemeier, David; Vieira, Maria Aparecida Ribeiro; Guimarães, Jorge Almeida

    2013-11-01

    The clinical manifestations of Lonomia obliqua caterpillar envenomation are systemic hemorrhage and acute kidney injury. In an effort to better understand the physiopathological mechanisms of envenomation, a rat model was established to study systemic tissue damage during L. obliqua envenomation. An array of acute venom effects was characterized, including biochemical, hematological, histopathological, myotoxic and genotoxic alterations. Rapid increases in serum alanine and aspartate transaminases, γ-glutamyl transferase, lactate dehydrogenase, hemoglobin, bilirubin, creatinine, urea and uric acid were observed, indicating that intravascular hemolysis and liver and kidney damage had occurred. Treatment with a specific antivenom (antilonomic serum) for up to 2 h post-venom injection neutralized the biochemical alterations. However, treatment after 6 h post-venom injection failed to normalize all biochemical parameters, despite its efficacy in reversing coagulation dysfunction. The hematological findings were consistent with hemolytic anemia and neutrophilic leukocytosis. The histopathological alterations were mainly related to hemorrhage and inflammation in the subcutaneous tissue, lung, heart and kidneys. Signs of congestion and hemosiderosis were evident in the spleen, and hemoglobin and/or myoglobin casts were also detected in the renal tubules. Increased levels of creatine kinase and creatine kinase-MB were correlated with the myocardial necrosis observed in vivo and confirmed the myotoxicity detected in vitro in isolated extensor digitorum longus muscles. Significant DNA damage was observed in the kidneys, heart, lung, liver and lymphocytes. The majority of the DNA lesions in the kidney were due to oxidative damage. The results presented here will aid in understanding the pathology underlying Lonomia's envenomation. PMID:23994591

  19. Impact of interleukin-6 promoter polymorphism and serum interleukin-6 level on the acute inflammation and neovascularization stages of patients with Eales’ disease

    PubMed Central

    Sen, Aditi; Paine, Suman Kalyan; Chowdhury, Imran Hussain; Mukherjee, Amrita; Choudhuri, Subhadip; Saha, Avijit; Mandal, Lakshmi Kanta

    2011-01-01

    Purpose To evaluate the role of interleukin-6 (IL-6) in the inflammatory and proliferative stages of Eales’ disease (ED) and to determine the influence of IL-6–174G/C polymorphism in the IL-6 and IL-6-regulated protein expression, as well as the development of ED. Methods One hundred and twenty-one patients diagnosed with ED, 223 matched healthy controls, and 16 control patients with macular holes were recruited from the eastern Indian population. Serum and vitreous levels of IL-6 and vascular endothelial growth factors (VEGF) were measured by enzyme-linked immunosorbent assay. Serum levels of high-sensitivity C-reactive protein (hsCRP) were measured by enzyme immunoassay. Subjects were genotyped for the IL-6–174G/C polymorphism (rs1800795) by a custom TaqMan single-nucleotide polymorphism (SNP) Genotyping Assays system. Results Serum IL-6 (p<0.0001), hsCRP (p<0.0001), and VEGF (p=0.0031) levels were significantly higher in the inflammatory stage of ED than in healthy controls. Serum IL-6 also significantly correlated with hsCRP (Spearman’s correlation coefficient; r=0.4992, p=0.0009), but not with VEGF in this stage in ED patients. At the proliferative stage of ED, significantly higher levels of vitreous IL-6 (p=<0.0001) and VEGF (p=<0.0001) were found compared with the vitreous of patients with macular holes. A significant correlation was observed between vitreous IL-6 and VEGF in ED patients (Spearman’s correlation coefficient; r=0.5834, p=0.0087). A statistically significant association was found between the −174GG genotype (p=0.006) and occurrence of ED. Mean serum and vitreous concentrations of IL-6 were also higher in the subjects with the GG genotype than in those with the GC or CC genotype in this population. Conclusions IL-6 expression, regulated by the allelic distribution of −174 loci and the enhanced level of IL-6, modulates CRP and VEGF concentration depending respectively on the acute inflammatory stimulation at the initial stage and

  20. Relationship between coronary flow reserve evaluated by phase-contrast cine cardiovascular magnetic resonance and serum eicosapentaenoic acid

    PubMed Central

    2013-01-01

    Background Long-term intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA) is associated with a low risk for cardiovascular disease. Phase-contrast cine cardiovascular magnetic resonance (PC cine CMR) can assess coronary flow reserve (CFR). The present study investigates the relationship between CFR evaluated by PC cine CMR and the serum EPA. Methods We studied 127 patients (male, 116 (91%); mean age, 72.2 ± 7.4 years) with known or suspected coronary artery disease (CAD). X-ray coronary angiography revealed no significant coronary arterial stenoses (defined as luminal diameter reduction ≥50% on quantitative coronary angiogram (QCA) analysis) in all study participants. Breath-hold PC cine CMR images of the coronary sinus (CS) were acquired to assess blood flow of the CS both at rest and during adenosine triphosphate (ATP) infusion. We calculated CFR as CS blood flow during ATP infusion divided by that at rest. Patients were allocated to groups according to whether they had high (n = 64, EPA ≥ 75.8 μg/mL) or low (n = 63, EPA < 75.8 μg/mL) median serum EPA. Results CFR was significantly lower in the low, than in the high EPA group (2.54 ± 1.00 vs. 2.91 ± 0.98, p = 0.038). Serum EPA positively correlated with CFR (R = 0.35, p < 0.001). We defined preserved CFR as > 2.5, which is the previously reported lower limit of normal flow reserve without obstructive CAD. Multivariate analysis revealed that EPA is an independent predictor of CFR > 2.5 (odds ratio, 1.01; 95% confidence interval, 1.00 – 1.02, p = 0.008). Conclusions The serum EPA is significantly correlated with CFR in CAD patients without significant coronary artery stenosis. PMID:24359564

  1. Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 1. High abundance proteins, acute phase proteins and peptidomics.

    PubMed

    Thomas, Funmilola Clara; Mullen, William; Tassi, Riccardo; Ramírez-Torres, Adela; Mudaliar, Manikhandan; McNeilly, Tom N; Zadoks, Ruth N; Burchmore, Richard; David Eckersall, P

    2016-08-16

    A peptidomic investigation of milk from an experimental model of Streptococcus uberis mastitis in dairy cows has incorporated a study of milk high abundance and acute phase (APP) proteins as well as analysis of low molecular weight peptide biomarkers. Intramammary infection (IMI) with S. uberis caused a shift in abundance from caseins, β-lactoglobulin and α-lactalbumin to albumin, lactoferrin and IgG with the increase in lactoferrin occurring last. The APP response of haptoglobin, mammary associated serum amyloid A3 and C-reactive protein occurred between 30-48 hours post challenge with peak concentrations of APPs at 72-96 hours post challenge and declined thereafter at a rate resembling the fall in bacterial count rather than the somatic cell count. A peptide biomarker panel for IMI based on capillary electrophoresis and mass spectrometry was developed. It comprised 77 identified peptides (IMI77) composed mainly of casein derived peptides but also including peptides of glycosylation dependent cell adhesion molecule and serum amyloid A. The panel had a biomarker classification score that increased from 36 hour to 81 hour post challenge, significantly differentiating infected from non-infected milk, thus suggesting potential as a peptide biomarker panel of bovine mastitis and specifically that of S. uberis origin. The use of omic technology has shown a multifactorial cross system reaction in high and low abundance proteins and their peptide derivatives with changes of over a thousand fold in analyte levels in response to S. uberis infection. PMID:27412456

  2. Targeting deeper the human serum fucome by a liquid-phase multicolumn platform in combination with combinatorial peptide ligand libraries.

    PubMed

    Selvaraju, Subhashini; El Rassi, Ziad

    2014-03-01

    Combinatorial peptide ligand library (CPLL) was evaluated as an off line step to narrow the differences of protein concentration in human serum prior to the capturing of human fucome from disease-free and breast cancer sera by a multicolumn platform via lectin affinity chromatography (LAC) followed by the fractionation of the captured glycoproteins by reversed phase chromatography (RPC). Two monolithic lectin columns specific to fucose, namely Aleuria aurantia lectin (AAL) and Lotus tetragonolobus agglutinin (LTA) columns were utilized to capture the fucome, which was subsequently fractionated by RPC yielding desalted fractions in volatile acetonitrile-rich mobile phase, which after vacuum evaporation were subjected to tryptic digestion prior to LC-MS/MS analysis. AAL has a strong affinity towards core fucosylated N-glycans and has a weak binding towards fucose in the outer arm while LTA can bind to glycans having fucose present in the outer arm. The combined strategy consisting of the CPLL, multicolumn platform and LC-MS/MS analysis permitted the identification of the differentially expressed proteins (DEPs) in breast cancer serum yielding 58 DEPs in both the LTA and AAL fractions with 6 DEPs common to both lectins. 17 DEPs were of the low abundance type, 16 DEPs of the borderline abundance type, 4 DEPs of the medium abundance type and 15 DEPs of the high abundance type. The remaining 6 DEPs are of unknown concentration. Only proteins exhibiting 99.9% protein identification probability, 95% peptide identification probability, and a minimum of 5 unique peptides were considered in finding the DEPs via scatterplots. PMID:24556279

  3. Targeting Deeper the Human Serum Fucome by a Liquid-phase Multicolumn Platform in Combination with Combinatorial Peptide Ligand Libraries

    PubMed Central

    Selvaraju, Subhashini; Rassi, Ziad El

    2014-01-01

    Combinatorial peptide ligand library (CPLL) was evaluated as an off line step to narrow the differences of protein concentration in human serum prior to the capturing of human fucome from disease-free and breast cancer sera by a multicolumn platform via lectin affinity chromatography (LAC) followed by the fractionation of the captured glycoproteins by reversed phase chromatography (RPC). Two monolithic lectin columns specific to fucose, namely Aleuria aurantia lectin (AAL) and Lotus tetragonolobus agglutinin (LTA) columns were utilized to capture the fucome, which was subsequently fractionated by RPC yielding desalted fractions in volatile acetonitrile-rich mobile phase, which after vacuum evaporation were subjected to tryptic digestion prior to LC-MS/MS analysis. AAL has a strong affinity towards core fucosylated N-glycans and has a weak binding towards fucose in the outer arm while LTA can bind to glycans having fucose present in the outer arm. The combined strategy consisting of the CPLL, multicolumn platform and LC-MS/MS analysis permitted the identification of the differentially expressed proteins (DEPs) in breast cancer serum yielding 58 DEPs in both the LTA and AAL fractions with 6 DEPs common to both lectins. 17 DEPs were of the low abundance type, 16 DEPs of the borderline abundance type, 4 DEPs of the medium abundance type and 15 DEPs of the high abundance type. The remaining 6 DEPs are of unknown concentration. Only proteins exhibiting 99.9% protein identification probability, 95% peptide identification probability, and a minimum of 5 unique peptides were considered in finding the DEPs via scatterplots. PMID:24556279

  4. Stir-bar supported micro-solid-phase extraction for the determination of polychlorinated biphenyl congeners in serum samples.

    PubMed

    Sajid, Muhammad; Basheer, Chanbasha

    2016-07-15

    In present work, a new configuration of micro-solid phase extraction was introduced and termed as stir-bar supported micro-solid-phase extraction (SB-μ-SPE). A tiny stir-bar was packed inside the porous polypropylene membrane along with sorbent material and the edges of membrane sheet were heat sealed to secure the contents. The packing of stir-bar inside the μ-SPE device does not allow the device to stick with the wall or any corner of the sample vial during extraction, which is, however, a frequent observation in routine μ-SPE. Moreover, it enhances effective surface area of the sorbent exposed to sample solution through continuous agitation (motion and rotation). It also completely immerses the SB-μ-SPE device in the sample solution even for non-polar sorbents. Polychlorinated biphenyls (PCBs) were selected as model compounds and the method performance was evaluated in human serum samples. After extraction, samples were analyzed by gas chromatography mass spectrometry (GC-MS). The factors that affect extraction efficiency of SB-μ-SPE were optimized. Under optimum conditions, a good linearity (0.1-100ngmL(-1)) with coefficients of determinations ranging from 0.9868 to 0.9992 was obtained. Limits of detections were ranged between 0.003 and 0.047ngmL(-1). Acceptable values for inter-day (3.2-9.1%) and intra-day (3.1-7.2%) relative standard deviations were obtained. The optimized method was successfully applied to determine the concentration of PCB congeners in human serum samples. PMID:27291862

  5. Acute effects of a single warm-water bath on serum adiponectin and leptin levels in healthy men: A pilot study

    NASA Astrophysics Data System (ADS)

    Shimodozono, Megumi; Matsumoto, Shuji; Ninomiya, Koji; Miyata, Ryuji; Ogata, Atsuko; Etoh, Seiji; Watanabe, Satoshi; Kawahira, Kazumi

    2012-09-01

    To preliminarily assess the acute effects of a single warm -water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 ± 6.0 years; mean body mass index, 21.6 ± 1.8 kg/m2). The subjects were immersed in tap water at 41°C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO2) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO2 (both P < 0.05), and remained significantly higher than those at baseline even 30 minutes after WWB with tap water ( P < 0.05). Adiponectin levels showed a slight, but not significant, increase both immediately after and 30 minutes after WWB with tap water or ISCO2. Some parameters, such as serum total cholesterol, red blood cell count, hemoglobin and hematocrit significantly increased immediately after WWB with tap water or ISCO2 (all P < 0.05), but they all returned to the baseline levels 30 minutes after bathing under both conditions. The sublingual temperature rose significantly after 10 minutes of WWB with tap water (0.96 ± 0.16°C relative to baseline, P < 0.01) and after the same duration of WWB with ISCO2 (1.24 ± 0.34°C relative to baseline, P < 0.01). These findings suggest that a single WWB at 41°C for 10 minutes may modulate leptin and adiponectin profiles in healthy men.

  6. Acute phase reactants in Sudanese children with severe protein-energy malnutrition*

    PubMed Central

    Suliman, Omer S. M.; Salih, Mustafa A. M.; Karrar, Zein A.; Mohammed, Abdelrahim O.; Helsing, Chrestover

    2011-01-01

    The pre-dietary rehabilitation levels of acute phase proteins (APP) namely, alpha-1-antitrypsin (AAT), orosomucoid (ORO), haptoglobin (HAP), fibrinogen (FIB) and C-reactive protein (CRP) in the plasma of Sudanese children with severe protein energy malnutrition (PEM) were compared with those of normal controls, and with the levels after dietary rehabilitation. Eighty one children were included in the study; 49 with severe PEM (23 with marasmus, 17 with marasmic-kwashiorkor and 9 with kwashiorkor), 13 with tuberculosis (TB) and 19 healthy children as controls. The study showed a high incidence of infections, especially acute respiratory infection (ARI), diarrhoeal diseases and intestinal parasites in the malnourished children. The mean plasma level of albumin was significantly lower in the malnourished children compared to controls (P<0.001), with kwashiorkor children showing the lowest mean level. This hypoalbuminaemia was significantly associated with the presence of ARI and intestinal parasites. The mean plasma levels of the APP, except FIB, were significantly higher in malnourished children than in controls, with higher levels associated with ARI and the presence of fever. Malnourished children with TB had significantly higher mean levels of the APP (AAT, HAP, FIB, CRP) compared to those without TB. The mean levels of HAP and AAT were significantly lower in the presence of diarrhoea, suggesting their loss in the stool. The mean levels of the APP after two weeks dietary rehabilitation and antimicrobial treatment showed a significant drop in only two of the APP, namely CRP, ORO, while FIB showed a significant rise.

  7. Quantifying and Qualifying the Preventive Effects of Acute-Phase Cognitive Therapy: Pathways to Personalizing Care

    PubMed Central

    Jarrett, Robin B.; Minhajuddin, Abu; Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.

    2016-01-01

    Objective To determine the extent to which prospectively identified responders to cognitive therapy (CT) for recurrent major depressive disorder (MDD) hypothesized to be lower risk show significantly less relapse/recurrence than treated higher risk counterparts across 32 months. Method Outpatients (N = 523), aged 18–70, with recurrent MDD received 12–14 weeks of CT. The last seven consecutive scores from the Hamilton Rating Scale for Depression (HRSD-17), were used to stratify/define responders (n = 290) into lower (seven HRSD-17 scores of ≤ 6; n = 49; 17%) and higher risk (n = 241; 83%). The lower risk entered the 32-month follow-up. Higher risk patients were randomized to 8 months of continuation-phase CT or clinical management plus double-blind fluoxetine or pill placebo, with a 24-month follow-up. Results Lower risk patients were significantly less likely to relapse over the first 8 months compared to higher risk (Kaplan-Meier [KM] estimates (i.e., 4.9%=lower risk; 22.1%= higher risk; log-rank χ2 = 6.83, p = .009). This increased risk was attenuated, but not completely neutralized, by active continuation-phase therapy. Over the subsequent 24 months, the lower and higher risk groups did not differ in relapse/recurrence risk. Conclusions Rapid and sustained acute-phase CT remission identifies responders who do not require continuation-phase treatment to prevent relapse (i.e., return of an index episode). To prevent recurrence (i.e., new episodes), however, strategic allocation and more frequent “dosing” of CT and/or targeted maintenance-phase treatments may be required. Longitudinal follow-up is recommended. PMID:26654211

  8. Clinical profile of chikungunya sequelae, association with obesity and rest during acute phase.

    PubMed

    Padmakumar, B; Jayan, Jacob B; Menon, Rejeesh; Kottarathara, Arun Jose

    2010-01-01

    The scarcity of literature regarding chikungunya infection sequelae makes it an unexplored area of medicine. We analyzed 1,111 patients with confirmed chikungunya sequelae and found a female predominance in those with sequelae which increased with age up to 40-50 years old, then decreased with further increase in age. In males age > 60 years old was the predominant age group affected. The symptoms were mainly symmetrical polyarthralgia of the proximal and distal interphalangeal joints. Dermatological manifestations were mainly hyper pigmented patches, generalized pruritus, and a maculopapular rash. Insomnia, fatigability and headache may indicate neurological involvement. Obesity gave an odds ratio of 2.07 for risk of arthritis. There was no significant benefit from rest during the acute phase (p < 0.001) of chikungunya in preventing chronicity of sequelae. Obesity as an independent risk factor for chronicity of chikungunya infection sequelae is a new finding. PMID:20578486

  9. Telemedicine in Acute-Phase Injury Management: A Review of Practice and Advancements

    PubMed Central

    Lewis, Erin R.; Thomas, Carlos A.; Mbarika, Victor W.A.

    2012-01-01

    Abstract Objectives: To offer a systematic review of the body of literature in the emerging field of telemedicine in the management of acute-phase injuries. Materials and Methods: We conducted a literature review. Results: Telemedicine has only recently been applied to the specialties of trauma, emergency care, and surgery. The potential benefits of telemedicine include a decrease in travel expenses, enhanced continuity of care, and increased access to specialized consultants in medically underserved and rural areas. Conclusions: There still exist barriers to the use of teletechnologies in medicine that limit their wider adoption. Poor infrastructure, limited equipment availability, and insufficient access to training and education for medical personnel have prevented wider use. PMID:22694296

  10. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    PubMed

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection. PMID:23381396

  11. Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss

    PubMed Central

    Jin, Yuanyuan; Lu, Ming

    2016-01-01

    Abstract Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined. The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment. Her symptoms and outcome measurements were improved every week and completely recovered after the last week. Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments. PMID:27368045

  12. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    NASA Astrophysics Data System (ADS)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  13. Serum metabonomics study of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced acute hepatotoxicity in rats by (1)H NMR analysis.

    PubMed

    Liang, Yong-Hong; Tang, Chao-Ling; Lu, Shi-Yin; Cheng, Bang; Wu, Fang; Chen, Zhao-Ni; Song, Fangming; Ruan, Jun-Xiang; Zhang, Hong-Ye; Song, Hui; Zheng, Hua; Su, Zhi-Heng

    2016-09-10

    Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the exact hepatoprotective mechanism of CS was still looking forward to further elucidation by far. In present work, metabonomic study of biochemical changes in the serum of carbon tetrachloride (CCl4)-induced acute liver injury rats after CS treatment were performed using proton nuclear magnetic resonance ((1)H-NMR) analysis. Metabolic profiling by means of principal components analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced by CS treatment. A total of 9 metabolites including isoleucine (1), lactate (2), alanine (3), glutamine (4), acetone (5), succinate (6), phosphocholine (7), d-glucose (8) and glycerol (9) were considered as potential biomarkers involved in the development of CCl4-induced acute liver injury. According to pathway analysis by metabolites identified and correlation network construction by Pearson's correlation coefficency matrix, alanine, aspartate and glutamate metabolism and glycerolipid metabolism were recognized as the most influenced metabolic pathways associated with CCl4 injury. As a result, notably, deviations of metabolites 1, 3, 4, 7 and 9 in the process of CCl4-induced acute liver injury were improved by CS treatment, which suggested that CS mediated synergistically abnormalities of the metabolic pathways, composed of alanine, aspartate and glutamate metabolism and glycerolipid metabolism. In this study, it was the first report to investigate the hepatoprotective effect of the CS based on metabonomics strategy, which may be a potentially powerful tool to interpret the action mechanism of traditional Chinese folk medicines. PMID:27399344

  14. Proteomics analysis of urine reveals acute phase response proteins as candidate diagnostic biomarkers for prostate cancer.

    PubMed

    Davalieva, Katarina; Kiprijanovska, Sanja; Komina, Selim; Petrusevska, Gordana; Zografska, Natasha Chokrevska; Polenakovic, Momir

    2015-01-01

    Despite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p < 0.05), 1.8 fold variation or more in abundance, showed 41 spots, corresponding to 23 proteins. The Ingenuity Pathway Analysis showed significant association with the Acute Phase Response Signaling pathway. Nine proteins with differential abundances were included in this pathway: AMBP, APOA1, FGA, FGG, HP, ITIH4, SERPINA1, TF and TTR. The expression pattern of 4 acute phase response proteins differed from the defined expression in the canonical pathway. The urine levels of TF, AMPB and HP were measured by immunoturbidimetry in an independent validation set. The concentration of AMPB in urine was significantly higher in PCa while levels of TF and HP were opposite (p < 0.05). The AUC for the individual proteins ranged from 0.723 to 0.754. The combination of HP and AMBP yielded the highest accuracy (AUC = 0.848), greater than PSA. The proposed biomarker set is quickly quantifiable and economical with potential to improve the sensitivity and specificity of PCa detection. PMID:25653573

  15. Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys.

    PubMed Central

    Gundel, R H; Wegner, C D; Torcellini, C A; Clarke, C C; Haynes, N; Rothlein, R; Smith, C W; Letts, L G

    1991-01-01

    This study examines the role of endothelial leukocyte adhesion molecule-1 (ELAM-1) in the development of the acute airway inflammation (cell influx) and late-phase airway obstruction in a primate model of extrinsic asthma. In animals sensitive to antigen, a single inhalation exposure induced the rapid expression of ELAM-1 (6 h) exclusively on vascular endothelium that correlated with the influx of neutrophils into the lungs and the onset of late-phase airway obstruction. In contrast, basal levels of ICAM-1 was constitutively expressed on vascular endothelium and airway epithelium before antigen challenge. After the single antigen exposure, changes in ICAM-1 expression did not correlate with neutrophil influx or the change in airway caliber. This was confirmed by showing that pretreatment with a monoclonal antibody to ICAM-1 did not inhibit the acute influx of neutrophils associated with late-phase airway obstruction, whereas a monoclonal antibody to ELAM-1 blocked both the influx of neutrophils and the late-phase airway obstruction. This study demonstrates a functional role for ELAM-1 in the development of acute airway inflammation in vivo. We conclude that, in primates, the late-phase response is the result of an ELAM-1 dependent influx of neutrophils. Therefore, the regulation of ELAM-1 expression may provide a novel approach to controlling the acute inflammatory response, and thereby, affecting airway function associated with inflammatory disorders, including asthma. Images PMID:1717514

  16. The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B.

    PubMed Central

    Fukuda, R; Ishimura, N; Nguyen, T X; Chowdhury, A; Ishihara, S; Kohge, N; Akagi, S; Watanabe, M; Fukumoto, S

    1995-01-01

    To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis. PMID:7774054

  17. Utility of the combination of serum highly-sensitive C-reactive protein level at discharge and a risk index in predicting readmission for acute exacerbation of COPD*,**

    PubMed Central

    Chang, Chun; Zhu, Hong; Shen, Ning; Han, Xiang; Chen, Yahong; He, Bei

    2014-01-01

    OBJECTIVE: Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources. Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients. This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD. METHODS: This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China. We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D). RESULTS: The final sample comprised 135 patients. Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period. The median (interquartile) time to readmission was 78 days (42-178 days). Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively). The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C. CONCLUSIONS: Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination. PMID:25410837

  18. Calcium and magnesium content of the uterine fluid and blood serum during the estrous cycle and pre-pubertal phase in water buffaloes

    PubMed Central

    Alavi Shoushtari, Sayed Mortaza; Asri Rezaie, Siamak; Khaki, Amir; Belbasi, Abulfazle; Tahmasebian, Hamid

    2014-01-01

    To investigate uterine fluid and serum calcium (Ca) and Magnesium (Mg) variations during the estrus cycle in water buffaloes, 71 genital tracts and blood samples were collected from the abattoir in Urmia. The phase of the estrous cycle was determined by examining ovarian structures. 18 animals were pro-estrous, 15 estrous, 16 met-estrous and 22 diestrous. The uterine fluid was collected by gentle scraping of the uterine mucosa with a curette. Blood serum and uterine fluid samples of 71 pre-pubertal buffalo calves were also collected and treated in similar manners. The mean ± SEM total serum and uterine fluid Ca in cyclic buffaloes were 8.68 ± 0.28 mg dL-1 and 8.10 ± 0.2 mg dL-1 vs. 6.76 ± 0.65 mg dL-1 and 7.90 ± 0.15 mg dL-1 in pre-pubertal calves, respectively. Blood serum Mg was not different in cyclic and pre-pubertal animals but the uterine fluid Mg in cyclic cows was higher than those in pre-pubertal calves. Serum Ca in pro-estrus and estrus were higher than those in other stages and also higher than those in the uterine fluid. The lowest Mg content of serum was recorded in diestrus, while in the uterine fluid it was observed in estrus. In all stages of estrous cycle except for estrus the uterine fluid Mg content was significantly higher than those of the serum. These results suggested that during the estrous cycle in the buffalo cows, Ca was passively secreted in uterine lumen and mostly dependent on blood serum Ca concentrations but Mg was secreted independently. The values (except for serum total Mg) also increased after puberty. PMID:25610582

  19. DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    EPA Science Inventory

    Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

    M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

  20. Prenatal transportation alters the acute phase response (APR) of bull calves exposed to a lipopolysaccharide (LPS) challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if prenatal transportation influences the acute phase response (APR) to a postnatal Lipopolysaccharide (LPS) challenge. Pregnant Brahman cows (n=96) matched by age and parity were separated into transported (TRANS; n=48; transported for 2 hours on gestational day...

  1. Proton magnetic resonance spectroscopy as a diagnostic biomarker in mild cognitive impairment following stroke in acute phase.

    PubMed

    Meng, Ningqin; Shi, Shengliang; Su, Ying

    2016-05-25

    To investigate proton magnetic resonance spectroscopy (HMRS) as a diagnostic biomarker to identify mild cognitive impairment (MCI) following stroke in the acute phase. A total of 72 stroke patients were recruited in the acute phase of stroke from the Department of Neurology, including 36 stroke patients with MCI and 36 stroke patients without MCI. All patients underwent brain MRI/MRS examination on a 3.0 T scanner and a neuropsychological test in the acute phase of stroke. Single-voxel HMRS was performed to obtain hippocampal metabolism intensities and brain infarcts were assessed on MRI. Group difference in metabolite ratios was analyzed using a T-test. Spearman rank correlation was used to study the correlation between metabolite ratios and Montreal Cognitive Assessment scores. The hippocampal n-acetylaspartate/creatine (NAA/Cr) ratio was found to be significantly lower in stroke patients with MCI compared with stroke patients without MCI (P<0.02). However, we found no differences in the metabolite ratios between hippocampus ipsilateral to infarctions and the contralateral side (P>0.05) in stroke patients with MCI. Furthermore, a correlation was found between hippocampal NAA/Cr ratios and Montreal Cognitive Assessment scores in stroke patients with MCI (P<0.01). HMRS could be a biomarker to identify MCI following stroke in the acute phase by capturing neurodegenerative changes. PMID:26981713

  2. The effect of feeding endophyte-infected fescue on the acute phase response to lipopolysaccharide in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angus heifers (n = 22; 292 ± 9.0 kg body weight) were paired by body weight and randomly placed on either an endophyte-infected (E+) or endophyte-free (E-) diet for 10 days to determine the influence of feeding endophyte-infected fescue on the physiological and acute phase responses of beef heifers ...

  3. Supplementation of Lactobacillus acidophilus fermentation product can attenuate the acute phase response following a lipopolysaccharide challenge in pigs.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if feeding a Lactobacillus acidophilus fermentation product to weaned pigs would reduce stress and acute phase responses (APR) following a lipopolysaccharide (LPS) challenge. Pigs (n=30; 6.4±0.1 kilograms body weight) were housed individually in pens with ad libi...

  4. METHODS FOR AQUATIC TOXICITY IDENTIFICATION EVALUATIONS: PHASE III TOXICITY CONFIRMATION PROCEDURES FOR SAMPLES EXHIBITING ACUTE AND CHRONIC TOXICITY

    EPA Science Inventory

    In 1989, the guidance document for acutely toxic effluents titled Methods for Aquatic Toxicity Identification Evaluations: Phase III Toxicity Confirmation Procedures was published (EPA, 1989D)This manual and its companion documents (EPA, 1991A; EPA, 1992; EPA, 1993A) are intended...

  5. Serum cholesterol and acute myocardial infarction: a case-control study from the GISSI-2 trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-Epidemiologia dei Fattori di Rischio dell'Infarto Miocardico Investigators.

    PubMed Central

    Nobili, A.; D'Avanzo, B.; Santoro, L.; Ventura, G.; Todesco, P.; La Vecchia, C.

    1994-01-01

    OBJECTIVE--To examine the role of serum cholesterol in acute myocardial infarction in a population of patients with no history of coronary heart disease and to establish the nature of this association, the degree of risk, and the possible interaction between serum cholesterol and other major risk factors for acute myocardial infarction. DESIGN--Case-control study. SETTING--90 hospitals in northern, central, and southern Italy. PATIENTS--916 consecutive cases of newly diagnosed acute myocardial infarction and 1106 hospital controls admitted to hospital with acute conditions not related to known or suspected risk factors for coronary heart disease. DATA COLLECTION--Data were collected with a structured questionnaire and blood samples were taken by venepuncture as soon as possible after admission to hospital from cases and controls. Blood cholesterol concentrations were available for 614 cases and 792 controls. RESULTS--After adjustment by logistic regression for sex, age, education, geographical area, smoking status, body mass index, history of diabetes and hypertension, and family history of coronary heart disease the estimated relative risks of acute myocardial infarction for quintiles of serum cholesterol (from lowest to highest) were 2.3 (95% confidence interval (CI) 1.6 to 3.4), 3.1 (95% CI 2.1 to 4.6), 4.1 (95% CI 2.8 to 6.0), and 5.2 (95% CI 3.5 to 7.7). The estimated relative risk across selected covariates increased from the lowest to the highest quintile of serum cholesterol particularly for men, patients under 55 years of age, and smokers. When the possible interaction of known risk factors with serum cholesterol was examined, smoking habits, diabetes, and hypertension had approximately multiplicative effects on relative risk. CONCLUSIONS--This study indicates that serum cholesterol was an independent risk factor for acute myocardial infarction. This association was linear, with no threshold level. Moreover, there was a multiplicative effect between

  6. Phase I study of idarubicin dose escalation for remission induction therapy in acute myeloid leukemia.

    PubMed

    Lee, Mark Hong; Kim, Sung-Yong

    2016-10-01

    The maximum tolerated dose (MTD) of idarubicin should be reevaluated in the treatment of acute myeloid leukemia (AML) in the era of granulocyte colony-stimulating factor and better supportive care. We conducted a phase I study to investigate the safety of escalating doses of idarubicin in combination with cytarabine 100 mg/m(2)/day for seven days for previously untreated AML. The starting dose of idarubicin was 12 mg/m(2)/day for three days with dose escalations by 3 mg/m(2)/day up to 18 mg/m(2)/day. The study design was adopted from traditional 3 + 3 design for phase I cancer clinical trials. The grade 4 hematologic toxicities were observed at all dose levels; however, these toxicities did not meet the criteria of the hematologic dose-limiting toxicities as defined in this study. There were no instances of grade 4 non-hematologic toxicities at any dose levels. The MTD of idarubicin was not reached in this trial. PMID:26750985

  7. Acute exposure to 2G phase shifts the rat circadian timing system

    NASA Technical Reports Server (NTRS)

    Hoban-Higgins, T. M.; Murakami, D. M.; Tandon, T.; Fuller, C. A.

    1995-01-01

    The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cures (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination, but exhibit a 'free-running' condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.

  8. Involvement of activated leukocytes in the regulation of plasma levels of acute phase proteins in microgravity simulation experiments

    NASA Astrophysics Data System (ADS)

    Larina, Olga; Bekker, Anna; Turin-Kuzmin, Alexey

    2016-07-01

    Earth-based studies of microgravity effects showed the induction of the mechanisms of acute phase reaction (APR). APR comprises the transition of stress-sensitive protein kinases of macrophages and other responsive cells into the active state and the phosphorylation of transcription factors which in turn stimulate the production of acute-phase reaction cytokines. Leukocyte activation is accompanied by the acceleration of the formation of oxygen radicals which can serve a functional indice of leukocyte cell state. The series of events at acute phase response result in selective changes in the synthesis of a number of secretory blood proteins (acute phase proteins, APPs) in liver cells thus contributing the recovery of homeostasis state in the organism. Earlier experiment with head-down tilt showed the increase in plasma concentrations of two cytokine mediators of acute phase response, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) being the outcome of the activation of producer cells, foremost, leukocytes. In experiment with 4-day dry immersion chemiluminescent (ChL) reply of the whole blood samples to a test stimulus were studied along with the measurements of plasma levels of APPs, namely, alpha1-antitrypsin (alpha1-AT), alpha1-acid glycoprotein (alpha1-AGP), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cer), haptoglobin (Hp), C3-complement component (C3), C-reactive protein (CRP). Eight individuals aged 21.2 ± 3.2 years were the test subjects in the investigation. Protein studies showed a noticeable increase in the mean plasma levels of all APPs measured in experiment thus producing the evidence of the activation of acute phase response mechanisms while individual patterns revealed variability during the immersion period. The overall trends were similar to these in the previous immersion series. The augment in the strength of signal in stimulated light emission tests was higher after 1- and 2-day of immersion exposure than before the

  9. Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2.

    PubMed Central

    Pruzanski, W; de Beer, F C; de Beer, M C; Stefanski, E; Vadas, P

    1995-01-01

    The acute-phase proteins serum amyloid A protein (SAA) and secretory phospholipase A2 (sPLA2) are simultaneously expressed during inflammatory conditions. SAA associates with high-density lipoprotein (HDL) altering its physicochemical composition. We found that purified acute-phase SAA, but not the constitutive form, markedly enhances the lipolytic activity of sPLA2 in a dose-related manner with phosphatidylcholine/lysophosphatidylcholine or phosphatidylethanolamine/lysophosphatidylethanolamine liposomal substrates. Normal HDL was found to reduce activity of sPLA2 in a dose-dependent manner, but when acute-phase HDL containing 27% SAA was tested, it enhanced sPLA2 activity. Immunopurified monospecific antibodies against SAA completely abolished the enhancing activity of SAA and acute-phase HDL. Given the central role of HDL in lipoprotein metabolism, the interaction between HDL, SAA and sPLA2 may account for changes detected in lipoprotein metabolism during the acute phase. PMID:7542869

  10. Preventive effect of the microalga Chlamydomonas debaryana on the acute phase of experimental colitis in rats.

    PubMed

    Avila-Román, Javier; Talero, Elena; Alcaide, Antonio; Reyes, Carolina de Los; Zubía, Eva; García-Mauriño, Sofía; Motilva, Virginia

    2014-10-14

    Inflammatory bowel diseases (IBD) are characterised by chronic uncontrolled inflammation of intestinal mucosa. Diet and nutritional factors have emerged as possible interventions for IBD. Microalgae are rich sources of n-3 PUFA and derived oxylipins. Oxylipins are lipid mediators involved in the resolution of many inflammatory disorders. The aim of the present study was to investigate the effects of the oxylipin-containing biomass of the microalga Chlamydomonas debaryana and its major oxylipin constituent, (9Z,11E,13S,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid ((13S)-HOTE), on acute 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Lyophilised microalgal biomass and (13S)-HOTE were administered by oral route 48, 24 and 1 h before the induction of colitis and 24 h later, and the rats were killed after 48 h. The treatment with the lyophilised microalga and (13S)-HOTE improved body-weight loss and colon shortening, as well as attenuated the extent of colonic damage and increased mucus production. Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase levels induced by TNBS, were also reduced after the administration of the lyophilised microalga or (13S)-HOTE. The anti-inflammatory effects of these treatments were confirmed by the inhibition of colonic TNF-α production. Moreover, lyophilised microalga or (13S)-HOTE down-regulated cyclo-oxygenase-2 and inducible nitric oxide synthase expression. The present study was the first to show the prophylactic effects of a lyophilised biomass sample of the microalga C. debaryana and the oxylipin (13S)-HOTE on TNBS-induced acute colitis in rats. Our findings suggest that the microalga C. debaryana or derived oxylipins could be used as nutraceuticals in the treatment of the active phase of IBD. PMID:25192306

  11. The Impact of Acute Phase Domain-Specific Cognitive Function on Post-stroke Functional Recovery

    PubMed Central

    Park, Jihong; Lee, Gangpyo; Lee, Shi-Uk

    2016-01-01

    Objective To assess whether the cognitive function in the acute stage evaluated by domain-specific neuropsychological assessments would be an independent predictor of functional outcome after stroke. Methods Forty patients underwent 4 domain-specific neuropsychological examinations about 3 weeks after the onset of stroke. The tests included the Boston Naming Test (BNT), the construction recall test (CRT), the construction praxis test (CPT), and the verbal fluency test (VFT). The Korean version of Modified Barthel Index (K-MBI) at 3 months and the modified Rankin Scale (mRS) at 6 months were investigated as functional outcome after stroke. Functional improvement was assessed using the change in K-MBI during the first 3 months and subjects were dichotomized into 'good status' and 'poor status' according to mRS at 6 months. The domain-specific cognitive function along with other possible predictors for functional outcome was examined using regression analysis. Results The z-score of CPT (p=0.044) and CRT (p<0.001) were independent predictors for functional improvement measured by the change in K-MBI during the first 3 months after stroke. The z-score of CPT (p=0.049) and CRT (p=0.048) were also independent predictors of functional status at post-stroke 6 months assessed by mRS. Conclusion Impairment in visuospatial construction and memory within one month after stroke can be an independent prognostic factor of functional outcome. Domain-specific neuropsychological assessments could be considered in patients with stroke in the acute phase to predict long-term functional outcome. PMID:27152270

  12. What is still missing in acute-phase treatment of stroke: a prospective observational study.

    PubMed

    Mazzucco, Sara; Turri, Giulia; Mirandola, Rina; Bovi, Paolo; Bisoffi, Giulia

    2013-04-01

    Early recognition of stroke symptoms and activation of emergency medical service (EMS) positively affects prognosis after a stroke. To assess stroke awareness among stroke patients and medical personnel in the catchment area of Verona Hospital and how it affects stroke care, we prospectively studied timing of acute stroke care in relation to patients' characteristics. Patients admitted to Medical Departments of Verona University Hospital between January 1st and December 31st 2009 with a diagnosis of TIA or stroke were enrolled. Outcome measures were: time between (i) symptoms onset and hospital arrival, (ii) hospital arrival and brain CT scan, blood examination, ECG and neurological evaluation. The following patient/event characteristics were also collected: means of hospital arrival, sex, age, degree of disability, type of event (first or recurrent) and acute-phase treatment. Of 578 patients providing complete information, 60 % arrived to the emergency department with the EMS (EMS+ group), while 40 % arrived on their own (EMS-). EMS+ group was older than EMS- (mean age 76.2, SD 13.2, vs. 72.3, SD 13, respectively), displayed more severe symptoms (mRS 4 vs. 2) and shorter time interval between symptoms onset and hospital arrival, hospital arrival and CT scan, ECG, laboratory tests and neurological evaluation (p < 0.0001); 22 % of the EMS+ patients were stroke recurrences versus 29 % of the EMS- (p = 0.058); 85 % of thrombolised patients were EMS+. We conclude that there is a lack of awareness of stroke symptoms and risks of recurrence even among patients who already had a stroke and among medical personnel. PMID:22466805

  13. Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

    PubMed Central

    Arponen, Otso; Muuronen, Antti; Taina, Mikko; Sipola, Petri; Hedman, Marja; Jäkälä, Pekka; Vanninen, Ritva; Pulkki, Kari; Mustonen, Pirjo

    2015-01-01

    Background Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism. Methods A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit. Results Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment. Conclusion IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology. PMID:25923658

  14. Association between Serum Ferritin and Contrast-Induced Nephropathy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Zhu, Boqian; Hou, Jiantong; Gong, Yaoyao; Yan, Gaoliang; Wang, Qingjie; Wang, Dong; Qiao, Yong; Chen, Yifei

    2016-01-01

    Background and Aims. CIN is a major and serious complication following PCI in patients with ACS. It is unclear whether a higher serum ferritin level is associated with an increased risk of CIN in high-risk patients. Thus, we conducted this study to assess the predictive value of SF for the risk of CIN after PCI. Methods. We prospectively examined SF levels in 548 patients with ACS before undergoing PCI. Multivariate logistic regression analysis was used to analyze the independent risk factors for CIN. The ROC analysis was performed to evaluate the predictive value of SF for CIN. Results. CIN occurred in 96 patients. Baseline SF was higher in patients who developed CIN compared to those who did not (257.05 ± 93.98 versus 211.67 ± 106.65; P < 0.001). Multivariate logistic regression analysis showed that SF was an independent predictor of CIN (OR, 1.008; 95% CI, 1.003–1.013; P = 0.002). The area under ROC curve for SF was 0.629, and SF > 180.9 μg/L predicted CIN with sensitivity of 80.2% and specificity of 41.4%. Conclusion. Our data show that a higher SF level was significantly associated with an increased risk of CIN after PCI. PMID:27547760

  15. Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels.

    PubMed

    Tang, Chao-Zhi; Zhang, Yu-Ling; Wang, Wen-Sheng; Li, Wei-Guo; Shi, Ji-Peng

    2016-05-01

    Inflammatory processes have fundamental roles in depression. The primary purpose of this study was to assess the serum levels of high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) at admission to the presence of poststroke depression (PSD). From December 2012 to December 2013, first-ever acute ischemic stroke patients who were admitted to the hospital within the first 24 h after stroke onset were consecutively recruited and followed up for 6 months. Serum levels of Hs-CRP and HCY were tested at admission. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression at 6 months after stroke. Ninety-five patients (42.0 %) showed depression (major + minor) at 6 months after admission, and in 69 patients (30.5 %), this depression was classified as major. In the 69 patients with major depression, our results showed significantly higher Hs-CRP and HCY levels at admission than patients without major depression. After adjusting all other possible covariates, Hs-CRP and HCY still were independent predicators of PSD with adjusted OR of 1.332 (95 % CI, 1.230-1.452; P < 0.001) and 1.138 (95 % CI, 1.072-1.274; P < 0.001), respectively. The area under the receiver operating characteristic curve values of Hs-CRP and HCY were 0.765 (95 % CI, 0.701-0.9825) and 0.684 (95 % CI, 0.610-0.757) for PSD, respectively. The prognostic accuracy of combined model (HCY and Hs-CRP) was higher compared to those biomarkers alone and other markers. Elevated serum levels of Hs-CRP and HCY at admission were found to be associated with depression 6 months after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients. PMID:25941076

  16. Separation of porcine parvovirus from bovine serum albumin using PEG-salt aqueous two-phase system.

    PubMed

    Vijayaragavan, K Saagar; Zahid, Amna; Young, Jonathan W; Heldt, Caryn L

    2014-09-15

    Vaccine production faces a challenge in adopting conventional downstream processing steps that can efficiently purify large viral particles. Some major issues that plague vaccine purification are purity, potency, and quality. The industry currently considers 30% as an acceptable virus recovery for a vaccine purification process, including all downstream processes, whereas antibody recovery from CHO cell culture is generally around 80-85%. A platform technology with an improved virus recovery would revolutionize vaccine production. In a quest to fulfill this goal, we have been exploring aqueous two-phase systems (ATPSs) as an optional mechanism to purify virus. ATPS has been unable to gain wide implementation mainly due to loss of virus infectivity, co-purification of proteins, and difficulty of polymer recycling. Non-enveloped viruses are chemically resistant enough to withstand the high polymer and salt concentrations that are required for effective ATPS separations. We used infectious porcine parvovirus (PPV), a non-enveloped, DNA virus as a model virus to test and develop an ATPS separation method. We successfully tackled two of the three main disadvantages of ATPS previously stated; we achieved a high infectious yield of 64% in a PEG-citrate ATPS process while separating out the main contaminate protein, bovine serum albumin (BSA). The most dominant forces in the separation were biomolecule charge, virus surface hydrophobicity, and the ATPS surface tension. Highly hydrophobic viruses are likely to benefit from the discovered ATPS for high-purity vaccine production and ease of implementation. PMID:25086421

  17. Enantioselective separation and determination of adrafinil and modafinil on Chiralcel OJ-H column in rat serum and urine using solid-phase extraction followed by HPLC.

    PubMed

    Rao, R Nageswara; Shinde, Dhananjay D

    2009-08-01

    A simple and rapid normal-phase HPLC method for enantiospecific separation of a psychostimulant, adrafinil (ADL), and its metabolite modafinil (MDL) in rat serum and urine was developed. The separation was accomplished on a normal-phase polysaccharide stationary phase Chiralcel OJ-H using n-hexane-ethanol (62:38 v/v) as a mobile phase at a flow rate of 1.0 mL/min. Detection was carried out at 225 nm using a photo diode array (PDA) detector. The elution order of the enantiomers was determined by a polarimeter connected in series with the PDA. ADL and its metabolite were recovered from rat serum and urine by solid phase extraction using Oasis HLB cartridges and the mean recoveries were >or=80%. The enantiomers were eluted within 15 min without any interference from endogenous substances. The calibration curves were linear (r(2) > 0.998) in the concentration range of 1.20-500 microg/mL for ADL and MDL. The assay was specific, accurate, precise and reproducible (intra- and inter-day precisions RSDs <7.2%). ADL in rat serum was stable over three freeze-thaw cycles at ambient temperature for 4 h. The method was successfully applied to pharmacokinetic studies of adrafinil after an oral administration to rats. PMID:19353685

  18. Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs: A Toxicogenomic Study

    PubMed Central

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew; Jensen, Keld A; Hougaard, Karin S; Vogel, Ulla; Yauk, Carole L; Wallin, Håkan

    2011-01-01

    Titanium dioxide nanoparticles (nanoTiO2) are used in various applications including in paints. NanoTiO2 inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface-coated nanoTiO2 on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 ± 2.9 (SEM) mg surface-coated nanoTiO2/m3 for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO2 was characterized using DNA microarrays and pathway-specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO2 exposure resulted in increased levels of mRNA for acute phase markers serum amyloid A-1 (Saa1) and serum amyloid A-3 (Saa3), several C-X-C and C-C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2-fold (adjusted P-value < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR-1, miR-449a and revealed dramatic induction of miR-135b (60-fold). Thus, inhalation of surface-coated nanoTiO2 results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. Mutagen., 2011. © 2011 Wiley-Liss, Inc.† PMID:21259345

  19. Phase I study of azacitidine and bortezomib in adults with relapsed or refractory acute myeloid leukemia

    PubMed Central

    Walker, Alison R.; Klisovic, Rebecca B.; Garzon, Ramiro; Schaaf, Larry J.; Humphries, Kristina; Devine, Steven M.; Byrd, John C.; Grever, Michael R.; Marcucci, Guido; Blum, William

    2013-01-01

    We previously reported that bortezomib indirectly modulates transcription of DNA methyltransferase 1 (DNMT). We designed a phase I study of azacitidine (a direct DNMT inhibitor) plus bortezomib in acute myeloid leukemia (AML) to determine safety and tolerability. Twenty-three adults with relapsed/refractory AML received azacitidine 75mg/m2 daily on days 1-7. Bortezomib was dose escalated from 0.7mg/m2 on days 2 and 5 to 1.3mg/m2 on days 2, 5, 9, and 12. The target dose was reached without dose limiting toxicities. Infection and/or febrile neutropenia were frequent. Patients received a median of 2 cycles of therapy (range, 1-12+). Five of 23 patients achieved remission including two with morphologic and cytogenetic complete response (CR) and three with CR and incomplete count recovery (CRi). Of CR/CRi responders with cytogenetic abnormalities at baseline, three of four achieved cytogenetic CR. The combination of azacitidine and bortezomib was tolerable and active in this cohort of poor-risk previously-treated AML patients. PMID:23952243

  20. NRF2 and the Phase II Response in Acute Stress Resistance Induced by Dietary Restriction.

    PubMed

    Hine, Christopher M; Mitchell, James R

    2012-06-19

    Dietary restriction (DR) as a means to increase longevity is well-established in a number of model organisms from yeast to primates. DR also improves metabolic fitness and increases resistance to acute oxidative, carcinogenic and toxicological stressors - benefits with more immediate potential for clinical translation than increased lifespan. While the detailed mechanism of DR action remains unclear, a conceptual framework involving an adaptive, or hormetic response to the stress of nutrient/energy deprivation has been proposed. A key prediction of the hormesis hypothesis of DR is that beneficial adaptations occur in response to an increase in reactive oxygen/nitrogen species (ROS). These ROS may be derived either from increased mitochondrial respiration or increased xenobiotic metabolism in the case of some DR mimetics. This review will focus on the potential role of the redox-sensing transcription factor NF-E2-related factor 2 (NRF2) and its control of the evolutionarily conserved antioxidant/redox cycling and detoxification systems, collectively known as the Phase II response, in the adaptive response to DR. PMID:23505614

  1. Mutational analysis of acute-phase response factor/Stat3 activation and dimerization.

    PubMed Central

    Sasse, J; Hemmann, U; Schwartz, C; Schniertshauer, U; Heesel, B; Landgraf, C; Schneider-Mergener, J; Heinrich, P C; Horn, F

    1997-01-01

    Signal transducer and transcription (STAT) factors are activated by tyrosine phosphorylation in response to a variety of cytokines, growth factors, and hormones. Tyrosine phosphorylation triggers dimerization and nuclear translocation of these transcription factors. In this study, the functional role of carboxy-terminal portions of the STAT family member acute-phase response factor/Stat3 in activation, dimerization, and transactivating potential was analyzed. We demonstrate that truncation of 55 carboxy-terminal amino acids causes constitutive activation of Stat3 in COS-7 cells, as is known for the Stat3 isoform Stat3beta. By the use of deletion and point mutants, it is shown that both carboxy- and amino-terminal portions of Stat3 are involved in this phenomenon. Dimerization of Stat3 was blocked by point mutations affecting residues both in the vicinity of the tyrosine phosphorylation site (Y705) and more distant from this site, suggesting that multiple interactions are involved in dimer formation. Furthermore, by reporter gene assays we demonstrate that carboxy-terminally truncated Stat3 proteins are incapable of transactivating an interleukin-6-responsive promoter in COS-7 cells. In HepG2 hepatoma cells, however, these truncated Stat3 forms transmit signals from the interleukin-6 signal transducer gp130 equally well as does full-length Stat3. We conclude that, dependent on the cell type, different mechanisms allow Stat3 to regulate target gene transcription either with or without involvement of its putative carboxy-terminal transactivation domain. PMID:9234724

  2. Reorganization of Motor Execution Networks During Sub-Acute Phase After Stroke.

    PubMed

    Cheng, Lin; Wu, Zhiyuan; Sun, Junfeng; Fu, Yi; Wang, Xinning; Yang, Guo-Yuan; Miao, Fei; Tong, Shanbao

    2015-07-01

    Numerous studies focused on brain reorganization after stroke from aspects of task-related brain activity and resting-state brain networks. However, studies focusing on the longitudinal reorganization of task-state brain networks were scarce. In this study, functional magnetic resonance imaging data were collected from twelve stroke patients during blocked finger-tapping task at four post-stroke time points (less than 10 days, around 2 weeks, 1 month and 3 months), respectively. The dynamic changes and prognostic value of the network parameters (i.e., topological parameters, functional connectivity and nodal parameters) in task-state motor execution networks were thoroughly evaluated. We found that the topological configuration (clustering coefficient and characteristic path length) of task-state motor execution networks underwent significant shift during stroke recovery. Especially, we found the topological configuration of task-state motor execution networks at the early recovery stage were capable of predicting the motor function restoration during sub-acute phase. In addition, we found increasing functional connectivity between ipsilesional cerebellum and motor cortices in task-state motor execution networks. In general, this study demonstrated the reorganization and prognostic value of task-state brain network after stroke, which provides new insights into understanding the brain reorganization and rehabilitation after stroke. PMID:26151748

  3. Swimming Exercise in the Acute or Late Phase after Sciatic Nerve Crush Accelerates Nerve Regeneration

    PubMed Central

    Teodori, Rosana Macher; Betini, Joice; de Oliveira, Larissa Salgado; Sobral, Luciane Lobato; Takeda, Sibele Yoko Mattozo; Montebelo, Maria Imaculada de Lima

    2011-01-01

    There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C (P < 0.01). The diameter of axons and nerve fibers was larger in CS1 (P < 0.01) and CS14 (P < 0.05) than in C, and myelin sheath thickness was lower in all crushed groups (P < 0.05). There was no functional difference between CS1 and CS14 (P > 0.05). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury. PMID:21876821

  4. Reentry of nondividing leukemic cells into a proliferative phase in acute childhood leukemia

    PubMed Central

    Saunders, E. F.; Mauer, A. M.

    1969-01-01

    Reentry of small leukemic blast cells into a proliferative phase was demonstrated in a 3 yr old girl with untreated acute lymphoblastic leukemia. Since the proliferating leukemic cell compartment in this disease is not self-maintaining, continual entry of cells into this compartment is necessary to prevent depletion of proliferating cells. In order to identify the source of replacement cells, the rate of change of tritiated thymidine-labeled cells in the proliferating compartment was observed by means of serial bone marrow samples under two conditions. In the first study period only 10% of small leukemic blast cells were labeled, and in the second study period 72% of this population had become lebeled. During the first period the proliferating blast cells were rapidly replaced by unlabeled cells, while during the second period the replacement cells were coming largely from a labeled cell source. The only identifiable source of cells for maintenance of the proliferating population which was virtually unlabeled during the first period and largely labeled during the second period was the population of small leukemic blast cells. The finding that the small blast cells are only temporarily nonproliferative could account for effectiveness of therapy directed primarily against a dividing cell population. Persistence of some cells with longer resting times into remission could provide a focus for subsequent relapse. PMID:5256065

  5. Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression.

    PubMed

    Michalovicz, Lindsay T; Konat, Gregory W

    2014-03-01

    We have previously shown that peripherally restricted acute phase response (APR) elicited by intraperitoneal (i.p.) injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to excitotoxic insult as seen from profoundly exacerbated kainic acid (KA)-induced seizures. In the present study, we found that this hypersusceptibility was protracted for up to 72 h. RT-PCR profiling of hippocampal gene expression revealed rapid upregulation of 23 genes encoding cytokines, chemokines and chemokine receptors generally within 6 h after PIC challenge. The expression of most of these genes decreased by 24 h. However, two chemokine genes, i.e., Ccl19 and Cxcl13 genes, as well as two chemokine receptor genes, Ccr1 and Ccr7, remained upregulated for 72 h suggesting their possible involvement in the induction and sustenance of seizure hypersusceptibility. Also, 12 genes encoding proteins related to glutamatergic and GABAergic neurotransmission featured initial upregulation or downregulation followed by gradual normalization. The upregulation of the Gabrr3 gene remained upregulated at 72 h, congruent with its plausible role in the hypersusceptible phenotype. Moreover, the expression of ten microRNAs (miRs) was rapidly affected by PIC challenge, but their levels generally exhibited oscillating profiles over the time course of seizure hypersusceptibility. These results indicate that protracted seizure susceptibility following peripheral APR is associated with a robust polygenic response in the hippocampus. PMID:24363211

  6. Acute phase lipocalin Ex-FABP is involved in heart development and cell survival.

    PubMed

    Gentili, C; Tutolo, G; Zerega, B; Di Marco, E; Cancedda, R; Cancedda, F Descalzi

    2005-03-01

    Ex-FABP is an extracellular fatty acid binding protein, expressed during chicken embryo development in cartilage, muscle fibers, and blood granulocytes. Transfection of chondrocytes and myoblasts with anti-sense Ex-FABP cDNA results in inhibition of cell proliferation and apoptosis induction. Ex-FABP expression is dramatically enhanced by inflammatory stimuli and in pathological conditions. In this paper, by in situ whole mount and immunohistochemistry analysis we show that, at early developmental stage, Ex-FABP is diffuse in all tissues of chick embryos. Particularly high level of transcript and protein are expressed in the heart. During acute phase response (APR) induced by endotoxin LPS injection, a marked increase of Ex-FABP mRNA was observed in embryos, highest Ex-FABP expression being in heart and liver. To investigate in vivo the biological role of Ex-FABP, we have directly microinjected chicken embryos with antibody against Ex-FABP. Almost 70% of chicken embryos died and the target tissue was the heart. We detected in heart of the treated embryos a significant increase of apoptotic cells and high level of fatty acids. We propose that the accumulation of fatty acid, specific ligand of Ex-FABP, in the cell microenvironment is responsible of heart cell death, and we suggest that Ex-FABP may act as a survival protein by playing a role as scavenger for fatty acids. PMID:15455366

  7. Acute phase proteins in naturally occurring respiratory disease of feedlot cattle.

    PubMed

    Idoate, Ignacio; Vander Ley, Brian; Schultz, Loren; Heller, Meera

    2015-02-15

    The aim of this study was to evaluate three acute phase proteins (APP) [haptoglobin (HPT), lipopolysaccharide binding protein (LBP) and transferrin (Tf)] in feedlot cattle with naturally occurring respiratory disease diagnosed by a calf health scoring chart (CHSC). Seventy-seven beef calves were observed for signs of Bovine Respiratory Disease (BRD) during the first 28 days after arrival at the feedlot. Fourteen cases and pen matched controls were selected based on the CHSC. BRD cases were defined as a score of ≥ 5, while controls were defined as a score ≤ 4. The mean CHSC score in cases was 6.9 which was significantly greater than the controls 2.8 (P < 0.01). Mean plasma LBP and HPT concentrations were significantly greater in cases than controls (P < 0.01). Our study results show that measurement of HPT and LBP could be useful in detecting respiratory disease in feedlot conditions. Transferrin concentrations between the two groups were not statistically different. PMID:25599608

  8. Evaluation of the Effects of Honey on Acute-Phase Deep Burn Wounds

    PubMed Central

    Nakajima, Yukari; Mukai, Kanae; Nasruddin; Komatsu, Emi; Iuchi, Terumi; Kitayama, Yukie; Sugama, Junko; Nakatani, Toshio

    2013-01-01

    This study aimed to clarify the effects of honey on acute-phase deep burn wounds. Two deep burn wounds were created on mice which were divided into four groups: no treatment, silver sulfadiazine, manuka honey, and Japanese acacia honey. Wound sizes were calculated as expanded wound areas and sampled 30 minutes and 1–4 days after wounding for histological observation. The wound sections were subjected to hematoxylin and eosin and immunohistological staining to detect necrotic cells, apoptotic cells, neutrophils, and macrophages. The no treatment group formed a scar. The redness around the wound edges in the silver sulfadiazine group was the most intense. All groups exhibited increased wound areas after wounding. The proportions of necrotic cells and the numbers of neutrophils in the manuka and acacia honey groups were lower than those in the no treatment and silver sulfadiazine groups until day 3; however, there were no significant differences between all groups on day 4. These results show that honey treatment on deep burn wounds cannot prevent wound progression. Moreover, comparing our observations with those of Jackson, there are some differences between humans and animals in this regard, and the zone of hyperemia and its surrounding area fall into necrosis, which contributes to burn wound progression. PMID:24348720

  9. NRF2 and the Phase II Response in Acute Stress Resistance Induced by Dietary Restriction

    PubMed Central

    Hine, Christopher M.; Mitchell, James R.

    2013-01-01

    Dietary restriction (DR) as a means to increase longevity is well-established in a number of model organisms from yeast to primates. DR also improves metabolic fitness and increases resistance to acute oxidative, carcinogenic and toxicological stressors - benefits with more immediate potential for clinical translation than increased lifespan. While the detailed mechanism of DR action remains unclear, a conceptual framework involving an adaptive, or hormetic response to the stress of nutrient/energy deprivation has been proposed. A key prediction of the hormesis hypothesis of DR is that beneficial adaptations occur in response to an increase in reactive oxygen/nitrogen species (ROS). These ROS may be derived either from increased mitochondrial respiration or increased xenobiotic metabolism in the case of some DR mimetics. This review will focus on the potential role of the redox-sensing transcription factor NF-E2-related factor 2 (NRF2) and its control of the evolutionarily conserved antioxidant/redox cycling and detoxification systems, collectively known as the Phase II response, in the adaptive response to DR. PMID:23505614

  10. Evaluating a novel treatment for coronary artery inflammation in acute Kawasaki disease: A Phase I/IIa trial of atorvastatin

    PubMed Central

    Tremoulet, Adriana H; Jain, Sonia; Burns, Jane C

    2016-01-01

    Introduction Since the 1980s, the primary treatment of acute Kawasaki disease (KD) has been intravenous immunoglobulin and aspirin. However, 5-10% of children with acute KD will develop coronary artery abnormalities despite treatment within the first ten days after fever onset. There is no approved adjunctive therapy to prevent progression of coronary artery damage in these patients Areas covered The rationale and study design of a Phase I/IIa trial of atorvastatin in children with acute KD and coronary artery inflammation is presented. The studies of host genetics and KD pathogenesis leading up to this trial are reviewed. Expert opinion The repurposing of well-studied drugs used in the adult population is a cost-effective and efficient strategy to identify new therapies for pediatric diseases. Exploiting the anti-inflammatory, non-lipid-lowering effects of statins may open up new applications for this class of drugs for the pediatric age group.

  11. Rest energy expenditure is decreased during the acute as compared to the recovery phase of sepsis in newborns

    PubMed Central

    2010-01-01

    Background Little is known with respect to the metabolic response and the requirements of infected newborns. Moreover, the nutritional needs and particularly the energy metabolism of newborns with sepsis are controversial matter. In this investigation we aimed to evaluate the rest energy expenditure (REE) of newborns with bacterial sepsis during the acute and the recovery phases. Methods We studied nineteen neonates (27.3 ± 17.2 days old) with bacterial sepsis during the acute phase and recovery of their illness. REE was determined by indirect calorimetry and VO2 and VCO2 measured by gas chromatography. Results REE significantly increased from 49.4 ± 13.1 kcal/kg/day during the acute to 68.3 ± 10.9 kcal/kg/day during recovery phase of sepsis (P < 0.01). Similarly, VO2 (7.4 ± 1.9 vs 10 ± 1.5 ml/kg/min) and VCO2 (5.1 ± 1.7 vs 7.4 ± 1.5 ml/kg/min) were also increased during the course of the disease (P < 0.01). Conclusion REE was increased during recovery compared to the sepsis phase. REE of septic newborns should be calculated on individualized basis, bearing in mind their metabolic capabilities. PMID:20653967

  12. Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice.

    PubMed Central

    Vogels, M T; Cantoni, L; Carelli, M; Sironi, M; Ghezzi, P; van der Meer, J W

    1993-01-01

    Treatment with a single low dose (80 to 800 ng) of interleukin-1 (IL-1) 24 h before a lethal bacterial challenge of granulocytopenic and normal mice enhances nonspecific resistance. Since IL-1 induces secretion of acute-phase proteins, liver proteins which possess several detoxifying effects, we investigated the role of these proteins in the IL-1-induced protection. Inhibition of liver protein synthesis with D-galactosamine (GALN) completely inhibited the IL-1-induced synthesis of acute-phase proteins. GALN pretreatment abolished the protective effect of IL-1 on survival completely (neutropenic mice infected with Pseudomonas aeruginosa) or partially (nonneutropenic mice infected with Klebsiella pneumoniae). Pretreatment with IL-6, a cytokine induced by IL-1, did not reproduce the protection offered after IL-1 pretreatment, nor did it enhance or deteriorate the IL-1-enhanced resistance to infection. A protective effect of IL-1 via effects on glucose homeostasis during the acute-phase response was investigated by comparing plasma glucose levels in IL-1-treated mice and control mice before and during infection. Although glucose levels in IL-1-pretreated mice were somewhat higher in the later stages of infection, no significant differences from levels in control mice were present, and the glucose levels in control-treated animals never fell to hypoglycemic values. We conclude that the IL-1-induced nonspecific resistance is mediated neither by the induction of IL-6 nor by the effects of IL-1 on glucose homeostasis. Acute-phase proteins generated after IL-1 pretreatment, however, seem to play a critical role in the IL-1-induced protection to infection. PMID:7509141

  13. Induction of several acute-phase protein genes by heavy metals: A new class of metal-responsive genes

    SciTech Connect

    Yiangou, Minas; Ge, Xin; Carter, K.C.; Papaconstantinou, J. Shriners Burns Institute, Galveston, TX )

    1991-04-16

    Acute-phase reactants, metallothioneins, and heat-shock proteins are the products of three families of genes that respond to glucocorticoids and cytokines. Metallothioneins and heat-shock proteins, however, are also stimulated by heavy metals whereas very little is known about the effect of heavy metals on acute-phase-reactant genes. The authors have studied the effect of heavy metals (Hg, Cd, Pb, Cu, Ni, and Zn) and Mg on the acute-phase reactants {alpha}{sub 1}-acid glycoprotein, C-reactive protein, {alpha}{sub 1}-antitrypsin and {alpha}{sub 1}-antichymotrypsin. {alpha}{sub 1}-Acid glycoprotein and C-reactive protein mRNA levels were increased severalfold in livers of heavy-metal-treated Balb/c mice. The strongest induction was mediated by Hg, followed in order of response by Cd > Pb > Cu > Ni > Zn > Mg. None of the metals affected the mRNA levels of albumin, {alpha}{sub 1}-antitrypsin, and {alpha}{sub 1}-antichymotrypsin. Furthermore, failure to repress albumin, a negative acute-phase reactant, indicated that the induction of these genes was not due to a metal-mediated inflammatory response. The metals also induced {alpha}{sub 1}-acid glycoprotein and C-reactive protein in adrenalectomized animals, indicating that induction by the heavy metals is not mediated by the glucocorticoid induction pathway. Sequence analysis has revealed a region of homology to metal-responsive elements in the {alpha}{sub 1}-acid glycoprotein and C-reactive protein promoters. The studies indicate that the induction of {alpha}{sub 1}-acid glycoprotein and C-reactive protein by heavy metals may be regulated by these metal-responsive elements at the level of transcription.

  14. Antibodies against acute phase proteins and their functions in the pathogenesis of disease: a collective profile of 25 different antibodies.

    PubMed

    Lakota, Katja; Zigon, Polona; Mrak-Poljsak, Katjusa; Rozman, Blaz; Shoenfeld, Yehuda; Sodin-Semrl, Snezna

    2011-10-01

    The acute phase response is a defense system in which the innate immune response is activated following injury or infection. Positive and negative acute phase proteins (APPs) are crucial for protecting the host organism, as well as returning it to homeostatic levels, the first with elevated concentrations and the latter with decreased concentrations during the acute phase. Reports about the presence of antibodies against APPs are known, however their individual, as well as potentially collective, pathological or physiological roles are still emerging. Some of these autoantibodies are specifically connected with diseases (such as pancreatic secretory trypsin inhibitor and C3, C4 nephritic factors), while others have been reported as natural antibodies. The persistent presence (even if only minor) of autoantibodies in healthy blood donors indicates an overlapping category of autoantibodies, which could become pathogenic, depending on the autoantibody characteristics such as avidity, epitope specificity, changes in the microenvironment leading to different oxidative status and others. This review uses the novel approach of studying the overall autoantibody population against APPs, their functions and connections to diseases. The primary function of autoantibodies against APPs (anti-APPs) is thought to promote their clearance, however autoantibodies against negative APPs have also been found and applying the same role to those is doubtful. There is also the theory of consumption in the stage of inflammation, which could be relevant to anti-APPs. Reports about protective roles of autoantibodies are also emerging, showing lowered levels of antibodies in diseases, which could be interesting for therapeutic intervention. PMID:21718807

  15. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury

    PubMed Central

    CHIHARA, Hideo; TAKAGI, Yasushi; NISHINO, Kazunari; YOSHIDA, Kazumichi; ARAKAWA, Yoshiki; KIKUCHI, Takayuki; TAKENOBU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either “with HAL suitability” or “without HAL suitability” based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID:26538291

  16. Detection of acute kidney injury in premature asphyxiated neonates by serum neutrophil gelatinase-associated lipocalin (sNGAL) – sensitivity and specificity of a potential new biomarker

    PubMed Central

    Pejović, Biljana; Erić-Marinković, Jelena; Pejović, Marija; Kotur-Stevuljević, Jelena; Peco-Antić, Amira

    2015-01-01

    Introduction Acute kidney injury (AKI) is common in neonatal intensive care units (NICU). In recent years, every effort is made for early detection of AKI. Our hypothesis was that serum neutrophil gelatinase-associated lipocalin (sNGAL) may be a reliable screening test for early diagnosis of AKI in premature neonates after perinatal asphyxia. Therefore, our aim was to assess the diagnostic accuracy of sNGAL for AKI in premature asphyxiated neonates. Materials and methods AKI was defined in the third day of life (DOL 3) as a serum creatinine (sCr) increase ≥ 26.5 μmol/L from baseline (the lowest previous sCr). According to the increase of sCr, AKI patients were divided in AKIN1 (sCr increase up to 1.9 baseline) and AKIN2 (sCr increase from 2.0 to 2.9 baseline). sNGAL levels were measured on DOL 1, 3 and 7. Results AKI was diagnosed in 73 (0.676) of 108 enrolled premature asphyxiated neonates. Sixty one patients (0.836) were classified in AKIN1 and 12 patients (0.164) in AKIN2. sNGAL reached the maximal concentrations on DOL 1 within 4 hours after admission to NICU, being higher in AKI compared with no-AKI group (160.8 ± 113.1 vs. 87.1 ± 81.6; P < 0.001) as well as in AKIN2 compared with AKIN1 group (222.8 ± 112.9 vs. 147.8 ± 109.9; P < 0.001). The best areas under the receiver operating characteristic curves (AUC) for prediction of AKI were 0.72 [95% (0.62-0.80) P < 0.001] on DOL1 at 2h and 0.72 [95% (0.63-0.80) P < 0.001] at 4th hour after admission respectively. The corresponding sNGAL cutoff concentrations were 84.87 ng/mL (sensitivity 69.0% and specificity 71.9%) and 89.43 ng/mL (sensitivity 65.7% and specificity 74.3%). Conclusions In premature asphyxiated neonates sNGAL measured within the first 4 hours of DOL 1 is predictive of the occurrence and severity of AKI. Therefore, plasma levels of NGAL may be used for early diagnosis of AKI in these patients. PMID:26525750

  17. A conceptual framework: the early and late phases of skeletal muscle dysfunction in the acute respiratory distress syndrome.

    PubMed

    Files, D Clark; Sanchez, Michael A; Morris, Peter E

    2015-01-01

    Patients with acute respiratory distress syndrome (ARDS) often develop severe diaphragmatic and limb skeletal muscle dysfunction. Impaired muscle function in ARDS is associated with increased mortality, increased duration of mechanical ventilation, and functional disability in survivors. In this review, we propose that muscle dysfunction in ARDS can be categorized into an early and a late phase. These early and late phases are based on the timing in relationship to lung injury and the underlying mechanisms. The early phase occurs temporally with the onset of lung injury, is driven by inflammation and disuse, and is marked predominantly by muscle atrophy from increased protein degradation. The ubiquitin-proteasome, autophagy, and calpain-caspase pathways have all been implicated in early-phase muscle dysfunction. Late-phase muscle weakness persists in many patients despite resolution of lung injury and cessation of ongoing acute inflammation-driven muscle atrophy. The clinical characteristics and mechanisms underlying late-phase muscle dysfunction do not involve the massive protein degradation and atrophy of the early phase and may reflect a failure of the musculoskeletal system to regain homeostatic balance. Owing to these underlying mechanistic differences, therapeutic interventions for treating muscle dysfunction in ARDS may differ during the early and late phases. Here, we review clinical and translational investigations of muscle dysfunction in ARDS, placing them in the conceptual framework of the early and late phases. We hypothesize that this conceptual model will aid in the design of future mechanistic and clinical investigations of the skeletal muscle system in ARDS and other critical illnesses. PMID:26134116

  18. Alterations in bovine platelet function and acute phase proteins induced by Pasteurella haemolytica A1.

    PubMed Central

    Cheryk, L A; Hooper-McGrevy, K E; Gentry, P A

    1998-01-01

    Platelet function was assessed by aggregometry in 10 Holstein calves before and after exposure to Pasteurella haemolytica (biotype A, serotype 1) by intrabronchial challenge. At 24 h after exposure the platelets had become more reactive to stimulation with known platelet agonists such as adenosine diphosphate (ADP) and platelet-activating factor (PAF) and the platelet aggregates that formed were more resistant to disaggregation. The activation of platelets was an early response in the challenged calves as platelet function had returned to pretreatment levels 72 h after exposure to the bacteria while the acute phase reactant proteins, haptoglobin and fibrinogen, were approaching their peak values and alpha 2-macroglobulin levels had also risen significantly (P < 0.05) at this time. The plasma levels of these proteins were still elevated and albumin levels were depressed 6 d post-treatment. At post-mortem all calves exhibited pneumonic tissue damage. When P. haemolytica leukotoxin was added directly to bovine platelet suspensions both spontaneous aggregation and an increase in the aggregation response to ADP and PAF stimulation were observed. The morphological appearance of the platelet aggregates exhibited the typical pattern for bovine platelets with 2 distinct zones of cells being visible within each aggregate. One zone contained platelets in which the cytoplasmic granules were still evident and the other zone contained irregularly shaped platelets devoid of granular content. In the latter zone, discrete gaps, or pores, were evident in the plasma membrane of numerous platelets. This pore formation is characteristic of leukotoxin action and is not observed in ADP or PAF induced aggregates. Images Figure 2. PMID:9442932

  19. Synthesis of acute-phase alpha 2-macroglobulin during inflammation and pregnancy.

    PubMed

    Panrucker, D E; Lorscheider, F L

    1983-01-01

    A recent investigation of acute-phase alpha 2-macroglobulin (AP alpha 2M) concentration in the rat during pregnancy demonstrated a bimodal distribution, for which we suggested a maternal source of AP alpha 2M in early gestation and a fetal source in late gestation. This interpretation was supported by the findings of the present study, which employed organ culture techniques, incorporation of [35S]methionine, immunoprecipitation of radioactivity, and fluorography to measure synthesis of AP alpha 2M in specific fetal, adult, and maternal tissues. Preliminary results indicated that in adult male rats treated with croton oil (compared with nontreated males), AP alpha 2M was synthesized in kidney, spleen, thymus, and lymphocytes by 48 hr post induction, but synthesis in the liver was not evident. In the pregnant rat from 12 to 16 days (compared with nonpregnant females), synthesis of AP alpha 2M was high in metrial gland, moderate in spleen, thymus and lymphocytes, and absent in liver; at 21 days, synthesis of AP alpha 2M in these four maternal tissues had declined. Fetal synthesis of AP alpha 2M in yolk sac (12 to 16 days) and in liver (15 to 16 days) was significantly elevated, and at 21 days fetal liver still displayed marked synthesis. These data are consistent with the interpretation that an early maternal source of AP alpha 2M synthesis is the metrial gland and that in the fetus both yolk sac and liver are major sources of AP alpha 2M, the latter tissue continuing synthesis into late gestation. Lymphopoietic and lymph-containing tissues appear to be major sites of AP alpha 2M synthesis during inflammation and pregnancy. PMID:6200027

  20. Nomothetic and Idiographic Symptom Change Trajectories in Acute-Phase Cognitive Therapy for Recurrent Depression

    PubMed Central

    Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.; Jarrett, Robin B.

    2013-01-01

    Objective We tested nomothetic and idiographic convergence and change in three symptom measures during acute-phase cognitive therapy (CT) for depression and compared outcomes among patients showing different change patterns. Method Outpatients (N = 362; 69% women; 85% white; age mean = 43 years) with DSM-IV recurrent major depressive disorder completed the Hamilton Rating Scale for Depression (Hamilton, 1960), Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh 1961), and Inventory for Depressive Symptomatology—Self-Report (Rush, Gullion, Basco, Jarrett, & Trivedi, 1996) on 14 occasions, and pre-/post-CT measures of social-interpersonal functioning and negative cognitive content. Results The three symptom measures marked the same severity and change constructs, and we offer improved formulas for inter-measure score conversions via their common factor. Pre-post CT symptom reductions were large (ds 1.71-1.92), and nomothetic symptom curves were log-linear (larger improvements earlier and smaller improvements later in CT). Nonetheless, only 30% of individual patients showed clear log-linear changes, whereas other patients showed linear (e.g., steady decreases; 20%), one-step (e.g., a quick drop; 16%), and unclassified (34%) patterns. Log-linear, linear, and one-step patients were generally similar to one another and superior to unclassified patients post-CT in symptom levels, response and stable remission rates, social-interpersonal functioning, and cognitive content (median d = 0.69). Conclusions Reaching a low-symptom “destination” at the end of CT via any coherent “path” is more important in the short-term than which path patients take. We discuss implications for theories of change, clinical monitoring of individuals’ progress in CT, and the need to investigate long-term outcomes of patients with differing symptom change patterns. PMID:23627652

  1. Diagnostic accuracy of porcine acute phase proteins in meat juice for detecting disease at abattoir.

    PubMed

    Gutiérrez, A M; Martínez-Subiela, S; Cerón, J J

    2015-07-01

    The aim of this work was to evaluate whether acute phase protein (APP) determinations could assist Official Veterinarians carrying out work in slaughterhouses. To test this hypothesis, the diagnostic accuracy of APP determinations in meat juice of pigs was analysed to differentiate between healthy and diseased pigs. One hundred and one pigs of two different origins were classified into two groups according to their health status (healthy and diseased pigs), which was determined by a veterinary clinical examination on the farm. To assess the pigs' immune status, against the main porcine diseases, serological analyses were monitored. A general idea of the degree of disease coverage was analysed by examining organ lesions postmortem. Haptoglobin (Hp) and C reactive protein (CRP) were measured in meat juice samples. 72.13 per cent of pigs appeared to be seropositive for the porcine respiratory and reproductive syndrome virus, and almost 86.2 per cent of them had concomitant infections with other pathogens, such as Porcine circovirus type 2 or Swine influenza virus. Median Hp and CRP concentrations were significantly higher in diseased animals at different stages of the production chain, when compared with levels found in healthy finishing pigs (P<0.0001). Receiver operating characteristic analysis showed the highest sensitivity-specificity pairs, nearly 80-90 per cent, at cut-off levels of 83 and 10 µg/ml for Hp and CRP determinations, respectively, with high AUCs 0.9. This cut-off could be useful for veterinary inspections at the time of slaughter, to differentiate between the carcase of a healthy animal and the carcase of an animal suffering from a systemic disease, which should be completely condemned. PMID:26101294

  2. Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity: Study Design

    PubMed Central

    2016-01-01

    Purpose Detecting sight-threatening retinopathy of prematurity (ROP) relies on a diagnostic examination (DE) performed by an experienced ophthalmologist. An alternative may be a telemedicine system where retinal images of at-risk infants are graded by readers to determine features of ROP indicating the need for a DE. Methods The multicenter “Telemedicine Approaches to Evaluating Acute-phase ROP” (e-ROP) Study is a cohort study of 2,000 infants with birth weights <1251g. At each visit, ophthalmologists perform DEs and non-physician imagers obtain iris and five retinal images with the disc positioned in the center, right, left, up anddown. Images are uploaded to a secure server for grading by non-physician readers for the detection of plus disease, stage 3 ROP and/or zone I disease, any of which indicates “referral-warranted ROP (RW-ROP).” Images from all infants with RW-ROP and a random sample of infants without RW-ROP (based on DEs) are selected for grading. Gradings are compared to DEs to determine the validity and evaluate reliability, feasibility, safety, and cost-effectiveness of the telemedicine system. Results e-ROP is conducted in 12 Clinical Centers in the US and Canada with Study Headquarters, the Data Coordinating Center and the Image Reading Center in Philadelphia and the ROP Data Center in Oklahoma City. 27 Study Center Coordinators, 34 ophthalmologists; 26 imagers, and 4 readers have been certified. All study data are submitted using a secure web-based system. Conclusion The design and findings of this study will be useful to conduct other ROP studies or evaluate telemedicine for other diseases. PMID:24955738

  3. Acute Phase Response and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure

    EPA Science Inventory

    Identification of biomarkers assists in the disease diagnosis and environmental health risk assessment. Exposure to Libby amphibole (LA) has been associated with increased cardiovascular mortality. We hypothesized that rats exposed to LA would present a unique serum proteomic pro...

  4. Acute Phase Response, Inflammation and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure

    EPA Science Inventory

    Background: Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. Objective: We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help ...

  5. Similarities in acute phase protein response during hibernation in black bears and major depression in humans: A response to underlying metabolic depression?

    USGS Publications Warehouse

    Tsiouris, J.A.; Chauhan, V.P.S.; Sheikh, A.M.; Chauhan, A.; Malik, M.; Vaughan, M.R.

    2004-01-01

    This study investigated the effects of hibernation with mild hypothermia and the stress of captivity on levels of six acute-phase proteins (APPs) in serial samples of serum from 11 wild and 6 captive black bears (Ursus americanus Pallas, 1780) during active and hibernating states. We hypothesize that during hibernation with mild hypothermia, bears would show an APP response similar to that observed in major depression. Enzyme-linked immunoabsorbent assay was used to measure alpha2-macroglobulin and C-reactive protein, and a nephelometer to measure alpha1-antitrypsin, haptoglobin, ceruloplasmin, and transferrin. Levels of all other proteins except ceruloplasmin were significantly elevated during hibernation in both wild and captive bears at the p < 0.05 to p < 0.001 level. Alpha 2-macroglobulin and C-reactive-protein levels were increased in captive versus wild bears in both active and hibernating states at the p < 0.01 to p < 0.0001 level. During hibernation with mild hypothermia, black bears do not show immunosuppression, but show an increased APP response similar to that in patients with major depression. This APP response is explained as an adaptive response to the underlying metabolic depression in both conditions. Metabolic depression in hibernating bears is suggested as a natural model for research to explain the neurobiology of depression.

  6. Receiver operating characteristic curve analysis to determine the diagnostic performance of serum haptoglobin concentration for the diagnosis of acute puerperal metritis in dairy cows.

    PubMed

    Burfeind, O; Sannmann, I; Voigtsberger, R; Heuwieser, W

    2014-10-01

    Acute puerperal metritis (APM) in dairy cows is characterized by fever and fetid vaginal discharge within 21 days in milk (DIM). Increased serum haptoglobin concentration (Hp) can support the diagnosis of APM. However, there is a dearth of information of the test performance of Hp as a measure for APM with a consistent definition and considering parity. The objective of this trial was to study the test performance of Hp to distinguish healthy cows from cows with APM. A total of 33 of 60 (55.0%) primiparous cows and 43 of 133 (32.3%) multiparous cows developed APM. Primiparous cows with APM had the greatest Hp. However, in primiparous cows Hp did not significantly differ between healthy cows (DIM 2: 1.49 ± 0.64 mg/mL; DIM 5: 2.13 ± 0.66 mg/mL; DIM 10: 1.46 ± 0.85 mg/mL) and cows with APM (DIM 2: 1.78 ± 0.62 mg/mL; DIM 5: 2.48 ± 0.64 mg/mL; DIM 10: 1.60 ± 0.81 mg/mL). In multiparous cows, Hp was greater in cows with APM (DIM 2: 1.27 ± 0.68 mg/mL; DIM 5: 1.89 ± 0.94 mg/mL; DIM 10: 1.23 ± 0.78 mg/mL) than in healthy cows (DIM 2: 0.99 ± 0.68 mg/mL; DIM 5: 1.10 ± 0.80 mg/mL; DIM 10: 0.83 ± 0.68 mg/mL). Sensitivity and specificity of Hp to diagnose APM in multiparous cows ranged from 72% to 79% and 54% to 71% on DIM 2, 5 and 10, respectively. PMID:25128191

  7. Determination of the maleic acid in rat urine and serum samples by isotope dilution-liquid chromatography-tandem mass spectrometry with on-line solid phase extraction.

    PubMed

    Chen, Hsin-Chang; Wu, Charlene; Wu, Kuen-Yuh

    2015-05-01

    A rapid and simple on-line solid-phase extraction coupled with isotope dilution-liquid chromatography-tandem mass spectrometry (SPE-ID-LC-MS/MS) method was developed to quantitate maleic acid in serum and urine of SpragueDawley (SD) rats. The aforementioned biological samples were spiked with (13)C2-maleic acid, vigorously vortexed, added with acetonitrile to precipitate proteins, and then injected into the on-line SPE-LC-MS/MS system for quantification. Upon validation, this method demonstrated excellent feasibility and sensitivity: calibration curves for maleic acid in serum and urine display excellent linearity with the coefficient of determination (R(2)) greater than 0.999; the limits of detection and quantitation (LOD and LOQ) for maleic acid were determined at 0.2 and 0.5μg L(-1), respectively. Additionally, intra-day accuracy for maleic acid in serum and urine samples ranged from 94.0% to 100.2% and 101.3% to 104.4%, respectively. Furthermore, inter-day accuracy ranged from 93.6% to 101.0% and from 102.3% to 111.4% in serum and urine samples, respectively. Intra-day precision %RSD of maleic acid in serum and urine samples was 13.8% or less, whereas the inter-day precision was 6.1% or less. The matrix effects were not found to be statistically significant (p=0.9145 and p=0.5378, correspondingly) based on the calculations of recovery functions. The collected serum and urine samples were analyzed using SPE-ID-LC-MS/MS. Our results reveal trace levels of maleic acid in the control rats, demonstrating that this method is capable of analyzing background levels of contaminants in biofluids with excellent sensitivity and specificity at part-per-billion levels concentrations in complex matrices. PMID:25702978

  8. Evaluation of serum neopterin, high-sensitivity C-reactive protein and thiobarbituric acid reactive substances in Egyptian patients with acute coronary syndromes

    PubMed Central

    Ragab, M; Hassan, H; Zaytoun, T; Refai, W; Rocks, B; Elsammak, M

    2005-01-01

    The present study evaluated serum neopterin, high-sensitivity C-reactive protein (hs-CRP) and thiobarbituric acid reactive substances (TBARS) in Egyptian patients with acute coronary artery disease. Thirty-six patients with unstable angina aged (mean ± SD) 61.3±9.4 years, 29 patients with myocardial infarction aged 58.2±8.7 years and 24 sex- and age-matched control subjects were included in the study. Neopterin levels were significantly higher in patients with myocardial infarction and those with unstable angina than in the healthy control group (P<0.001). The serum level of neopterin in the control group (median [range]) was 3.25 nmol/L (1.25 nmol/L to 5.4 nmol/L), whereas in patients with unstable angina and those with myocardial infarction, neopterin levels were 10.4 nmol/L (3.5 nmol/L to 15.2 nmol/L) and 12.6 nmol/L (3.25 nmol/L to 17.8 nmol/L), respectively. Levels of hs-CRP and TBARS were also significantly higher in patients with unstable angina and those with myocardial infarction than in the healthy control group (P<0.01). The medians (ranges) of hs-CRP were 4.8 mg/L (2.5 mg/L to 9.9 mg/L), 12.0 mg/L (4.6 mg/L to 31.0 mg/L) and 12.3 mg/L (7.5 mg/L to 32.1 mg/L) in the control group, patients with unstable angina and those with myocardial infarction, respectively. The means ± SD of TBARS in the control group, patients with unstable angina and those with myocardial infarction were 0.64±0.17 μmol/L, 1.17±0.31 μmol/L and 1.17±0.49 μmol/L, respectively. TBARS positively correlated with hs-CRP and neopterin levels. Furthermore, when both patients and controls were classified according to their smoking status, significantly higher levels of neopterin and TBARS were found in the smokers of each subgroup than in the nonsmokers. In conclusion, the present study found a higher level of neopterin, hs-CRP and TBARS in patients with coronary artery disease. Serum neopterin and hs-CRP positively correlated with the level of TBARS. The authors suggest that

  9. Serum Shiga toxin 2 values in patients during the acute phase of diarrhoea-associated hemolytic uremic syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aim: Shiga toxins, Stx-1 and Stx-2, by injuring endothelial cells mainly of the glomeruli, are considered as the cause of D+HUS. After passing through the intestinal wall, Stxs have to be delivered via the systemic circulation to the target organs. This study was aimed at measuring free Stx-2 in ser...

  10. Serum Shiga toxin 2 values in patients during the acute phase of post-diarrheal hemolytic uremic syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Shiga toxins (Stxs) produced by Shiga toxin-producing Escherichia coli (STEC) are considered as the main causative agent, leading to the development of the hemolytic uremic syndrome (HUS); these toxins injure endothelial cells mainly the glomeruli. After passing through the intestinal wall, Stxs hav...

  11. Arterial stiffness during acute and recovery phases of children with rheumatic fever.

    PubMed

    Ibrahim, N N I N; Jaafar, H; Rasool, A H; Wong, A R

    2016-02-01

    Acute rheumatic fever (ARF) is associated with systemic inflammation and arterial stiffness during the acute stage. It has not been reported if arterial stiffness remains after recovery. The aim of this study was to determine the arterial stiffness during acute stage and 6 months after recovery from ARF. Arterial stiffness was assessed by carotid femoral pulse wave velocity (PWV) in 23 ARF patients during the acute stage of ARF and 6 months later. Simultaneously, erythrocyte sedimentation rate (ESR) and other anthropometric measurements were taken during both stages. There was a significant reduction in PWV; 6.5 (6.0, 7.45) m/s to 5.9 (5.38, 6.48) m/s, p=0.003 6 months after the acute stage of ARF. Similarly, ESR was also significantly reduced from 92.0 (37.5, 110.50) mm/hr to 7.0 (5.0, 16.0) mm/hr, p=0.001. In conclusion, arterial stiffness improved 6 months after the acute stage with routine aspirin treatment; this correlates well with the reduction in systemic inflammation. PMID:27130739

  12. The effects of acute-phase inducers and dimethyl sulphoxide on delta-aminolaevulinate synthase activity in human HepG2 hepatoma cells.

    PubMed Central

    Iwasa, F; Sassa, S; Kappas, A

    1989-01-01

    The effects of acute-phase inducers and dimethyl sulphoxide (Me2SO) on delta-aminolaevulinate (ALA) synthase in HepG2 cells were examined. Treatment of cells with Me2SO resulted in a significant increase in ALA synthase activity. Interleukin-6 increased ALA synthase activity only slightly, but it substantially potentiated the induction of ALA synthase by Me2SO. These data suggest that ALA synthase activity in liver is altered during acute-phase reactions. PMID:2541694

  13. Determination of anethole in serum samples by headspace solid-phase microextraction-gas chromatography-mass spectrometry for congener analysis.

    PubMed

    Schulz, Katja; Schlenz, Katja; Metasch, Robert; Malt, Steffen; Römhild, Wolfgang; Dressler, Jan

    2008-07-25

    A rapid headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method has been developed for the determination of anethole in serum samples. Anethole is a characteristic marker for the consumption of aniseed spirits. This method enabled the detection of anethole with a limit of detection (LoD) of 3.6 ng/ml and a limit of quantification (LoQ) of 5.3 ng/ml in serum samples with a good degree of precision intraday (2.8%) and interday (4.5%). Experiments were conducted with one volunteer, in which the subject consumed the alcoholic drink ouzo on 3 different days under controlled conditions. At defined intervals, blood samples were taken from the subject. Using these blood samples, the concentration-time profiles for anethole were determined. In blood samples taken from 50 drivers who claimed to have consumed drinks containing anethole (ouzo, raki and the German aniseed liqueur "Küstennebel") before the taking of the blood sample, anethole was detected in the serum in concentrations of between 5.4 and 17.6 ng/ml in 10 cases. This is the first report describing the qualitative and quantitative determination of a beverage-characteristic aroma compound - in this case anethole - in serum samples after consumption of alcoholic beverages. PMID:18571658

  14. Copper and zinc concentrations in uterine fluid and blood serum during the estrous cycle and pre-pubertal phase in water buffaloes.

    PubMed

    Alavi Shoushtari, Sayed Mortaza; Asri Rezaie, Siamak; Khaki, Amir; Belbasi, Abulfazl; Tahmasebian, Hamid

    2015-01-01

    To investigate uterine fluid and serum copper (Cu) and zinc (Zn) variations during the estrous cycle in water buffaloes, 71 genital tracts and blood samples were collected from the abattoir in Urmia, Iran. The phase of the estrous cycle was determined by examining ovarian structures; 18, 15, 16 and 22 were pro-estrous, estrous, met-estrous and diestrous, respectively. The uterine fluid was collected by gentle scraping of the uterine mucosa with a curette. Blood serum and uterine fluid samples of 71 pre-pubertal buffalo calves were also collected and treated in similar manners. The mean (± SEM) total serum (77.10 ± 1.50 µg dL(-1)) and uterine fluid (296.40 ± 9.40 μg dL(-1)) Cu in cyclic cows was higher than the values of 54.00 ± 1.10 μg dL(-1) and 133.40 ± 5.70 μg dL(-1) in pre-pubertal calves, respectively. Blood serum (114.60 ± 3.20 μg dL(-1)) and the uterine fluid (349.90 ± 8.90 μg dL(-1)) Zn content in cyclic cows were also higher than those (98.80 ± 1.50 μg dL(-1) and 246.6 ± 4.50 μg dL(-1) respectively) in pre-pubertal calves. Serum Cu in pro-estrus and estrus were lower than those in other stages and also lower than those in the uterine fluid. The lowest serum Zn content was recorded in pro- and met-estrus, while in the uterine fluid it was observed in estrus. In all stages of estrous cycle the uterine fluid Zn content was significantly higher than those of the serum. These results suggested that during the estrous cycle in the buffalo cows, Cu and Zn were actively secreted in uterine lumen and were not dependent on blood serum. The values also increased after puberty. PMID:26893810

  15. Copper and zinc concentrations in uterine fluid and blood serum during the estrous cycle and pre-pubertal phase in water buffaloes

    PubMed Central

    Alavi Shoushtari, Sayed Mortaza; Asri Rezaie, Siamak; Khaki, Amir; Belbasi, Abulfazl; Tahmasebian, Hamid

    2015-01-01

    To investigate uterine fluid and serum copper (Cu) and zinc (Zn) variations during the estrous cycle in water buffaloes, 71 genital tracts and blood samples were collected from the abattoir in Urmia, Iran. The phase of the estrous cycle was determined by examining ovarian structures; 18, 15, 16 and 22 were pro-estrous, estrous, met-estrous and diestrous, respectively. The uterine fluid was collected by gentle scraping of the uterine mucosa with a curette. Blood serum and uterine fluid samples of 71 pre-pubertal buffalo calves were also collected and treated in similar manners. The mean (± SEM) total serum (77.10 ± 1.50 µg dL-1) and uterine fluid (296.40 ± 9.40 μg dL-1) Cu in cyclic cows was higher than the values of 54.00 ± 1.10 μg dL-1 and 133.40 ± 5.70 μg dL-1 in pre-pubertal calves, respectively. Blood serum (114.60 ± 3.20 μg dL-1) and the uterine fluid (349.90 ± 8.90 μg dL-1) Zn content in cyclic cows were also higher than those (98.80 ± 1.50 μg dL-1 and 246.6 ± 4.50 μg dL-1 respectively) in pre-pubertal calves. Serum Cu in pro-estrus and estrus were lower than those in other stages and also lower than those in the uterine fluid. The lowest serum Zn content was recorded in pro- and met-estrus, while in the uterine fluid it was observed in estrus. In all stages of estrous cycle the uterine fluid Zn content was significantly higher than those of the serum. These results suggested that during the estrous cycle in the buffalo cows, Cu and Zn were actively secreted in uterine lumen and were not dependent on blood serum. The values also increased after puberty. PMID:26893810

  16. Acute social stress before the planning phase improves memory performance in a complex real life-related prospective memory task.

    PubMed

    Glienke, Katharina; Piefke, Martina

    2016-09-01

    Successful execution of intentions, but also the failure to recall are common phenomena in everyday life. The planning, retention, and realization of intentions are often framed as the scientific concept of prospective memory. The current study aimed to examine the influence of acute stress on key dimensions of complex "real life" prospective memory. To this end, we applied a prospective memory task that involved the planning, retention, and performance of intentions during a fictional holiday week. Forty healthy males participated in the study. Half of the subjects were stressed with the Socially Evaluated Cold Pressor Test (SECPT) before the planning of intentions, and the other half of the participants underwent a control procedure at the same time. Salivary cortisol was used to measure the effectiveness of the SECPT stress induction. Stressed participants did not differ from controls in planning accuracy. However, when we compared stressed participants with controls during prospective memory retrieval, we found statistically significant differences in PM across the performance phase. Participants treated with the SECPT procedure before the planning phase showed improved prospective memory retrieval over time, while performance of controls declined. Particularly, there was a significant difference between the stress and control group for the last two days of the holiday week. Interestingly, control participants showed significantly better performance for early than later learned items, which could be an indicator of a primacy effect. This differential effect of stress on performance was also found in time- and event-dependent prospective memory. Our results demonstrate for the first time, that acute stress induced before the planning phase may improve prospective memory over the time course of the performance phase in time- and event-dependent prospective memory. Our data thus indicate that prospective memory can be enhanced by acute stress. PMID:27370532

  17. Dual-phase CT for the assessment of acute vascular injuries in high-energy blunt trauma: the imaging findings and management implications.

    PubMed

    Iacobellis, Francesca; Ierardi, Anna M; Mazzei, Maria A; Magenta Biasina, Alberto; Carrafiello, Gianpaolo; Nicola, Refky; Scaglione, Mariano

    2016-05-01

    Acute vascular injuries are the second most common cause of fatalities in patients with multiple traumatic injuries; thus, prompt identification and management is essential for patient survival. Over the past few years, multidetector CT (MDCT) using dual-phase scanning protocol has become the imaging modality of choice in high-energy deceleration traumas. The objective of this article was to review the role of dual-phase MDCT in the identification and management of acute vascular injuries, particularly in the chest and abdomen following multiple traumatic injuries. In addition, this article will provide examples of MDCT features of acute vascular injuries with correlative surgical and interventional findings. PMID:26882960

  18. Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1123

    PubMed Central

    Shaikh, Nishat; Jensen, Christopher D; Volberg, Vitaly; Holland, Nina

    2011-01-01

    Background: Glutathione S-transferases (GSTs) detoxify environmental chemicals and are involved in oxidative stress pathways. Deletion polymorphisms affect enzyme activities and have been associated with risk of disease. Objective: The objective was to clarify whether biomarkers of oxidation, antioxidation, inflammation, and nutritional factors differ by GST genotype in healthy adults. Design: Subjects (n = 383) consisted of nonsmokers and nonusers of antiinflammatory drugs and antioxidant vitamin supplements. Deletion polymorphisms of GSTM1 and GSTT1 were genotyped. F2-isoprostanes, malondialdehyde, C-reactive protein, serum vitamin C, carotenoids, tocopherols, and other nutritional factors were assessed. Results: The concentration of serum vitamin C was higher in persons with the inactive GSTM1-0 genotype (P = 0.006). This relation was unchanged after adjustment for age, sex, BMI, or dietary vitamin C. F2-isoprostanes and malondialdehyde were lower in the GSTM1-0 and GSTT1-0 groups, respectively, but significance was lost after control for serum vitamin C. The dual deletion, GSTM1-0/GSTT1-0 (n = 37), was associated with higher serum iron and total and LDL-cholesterol concentrations (all P < 0.01) and lower malondialdehyde concentrations, which persisted after adjustment for age, sex, BMI, and serum vitamin C. Carotenoids and α- and γ-tocopherols were not associated with either genotype. Conclusions: Oxidative stress and inflammation biomarkers differ by GST genotype, but serum vitamin C appears to be the most consistent factor. Examination of other relevant genes may be needed to understand the concentration and function of ascorbic acid in the GST enzyme system. This trial is registered at clinicaltrials.gov as NCT00079963. PMID:21813807

  19. Determination of aluminum in the human serum of a dialysis patient by ion-pair reversed-phase partition high-performance liquid chromatography.

    PubMed

    Kaneko, E; Hoshino, H; Yotsuyanagi, T; Gunji, N; Sato, M; Kikuta, T; Yuasa, M

    1991-10-15

    An ion-pair reversed-phase partition high-performance liquid chromatography-spectrophotometric method is described for the determination of aluminum in human serum, based on its complexation with 2,2'-dihydroxyazobenzene. The chelate is separated on C18-bonded silica packing by using an aqueous methanol mobile phase containing tetrabutylammonium bromide and is detected with 0.005 AU full-scale at 510 nm. The proposed system offers a simple, sensitive, and selective method. The detection limits defined as twice the standard deviation of the blank signal, are 0.2 micrograms L-1 in pure solution and 6 micrograms L-1 in serum. The sample solution is prepared from 0.4 mL of serum after protein precipitation with hydrochloric acid and methanol. There was good agreement between the values obtained by this method and graphite furnace atomic absorption spectrophotometry. The aluminum concentrations in 121 patients on hemodialysis were 6-201 micrograms L-1. PMID:1759707

  20. A fast method for analysing six perfluoroalkyl substances in human serum by solid-phase extraction on-line coupled to liquid chromatography tandem mass spectrometry.

    PubMed

    Bartolomé, Mónica; Gallego-Picó, Alejandrina; Huetos, Olga; Lucena, Miguel Ángel; Castaño, Argelia

    2016-03-01

    We have developed and validated an on-line TurboFlow solid-phase extraction procedure coupled to high-performance liquid chromatography with tandem mass spectrometry for the analysis of six perfluoroalkyl substances (PFAS), two sulfonates (perfluorooctane sulfonate and perfluorohexane sulfonate), three carboxylates (perfluorooctanoic acid, perfluorononanoic acid and perfluorodecanoic acid), and one sulfonamide (N-methylperfluorooctane sulfonamide), in human serum samples. This method requires only 100 μL of sample and involves a short pre-treatment with acetonitrile followed by addition of a labelled internal standard for quantification and ultracentrifugation. All PFAS were detected with a run time of 8.5 min. Linearity ranges stay between 0.1 and 20 μg L(-1) (R (2) > 0.9960). Recoveries were determined by spiking blank serum samples with a mixture of six PFAS and found to be in the range 96-110 % for all compounds. Isotopic dilution was used to quantify the selected analytes. The low limits of quantification obtained, between 0.16 and 0.34 μg L(-1), small volume of sample required and short run time used (from two to three times shorter than any other described method), make this validated method highly recommended for human biomonitoring studies. Graphical Abstract System solid phase extraction on line coupled LC-MS/MS to analyse six perfluoroalkyl substances in human serum. PMID:26790871

  1. High-Resolution Transcriptomic Analysis of the Adaptive Response of Staphylococcus aureus during Acute and Chronic Phases of Osteomyelitis

    PubMed Central

    Szafranska, Anna K.; Oxley, Andrew P. A.; Chaves-Moreno, Diego; Horst, Sarah A.; Roßlenbroich, Steffen; Peters, Georg; Goldmann, Oliver; Rohde, Manfred; Sinha, Bhanu; Pieper, Dietmar H.; Löffler, Bettina; Jauregui, Ruy; Wos-Oxley, Melissa L.

    2014-01-01

    ABSTRACT Osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. In this study, we investigated the in vivo transcriptional adaptation of S. aureus during bone infection. To this end, we determined the transcriptome of S. aureus during the acute (day 7) and chronic (day 28) phases of experimental murine osteomyelitis using RNA sequencing (RNA-Seq). We identified a total of 180 genes significantly more highly expressed by S. aureus during acute or chronic in vivo infection than under in vitro growth conditions. These genes encoded proteins involved in gluconeogenesis, proteolysis of host proteins, iron acquisition, evasion of host immune defenses, and stress responses. At the regulatory level, sarA and -R and saeR and -S as well as the small RNA RsaC were predominantly expressed by S. aureus during in vivo infection. Only nine genes, including the genes encoding the arginine deiminase (ADI) pathway and those involved in the stringent response, were significantly more highly expressed by S. aureus during the chronic than the acute stage of infection. Analysis by quantitative reverse transcription-PCR (qRT-PCR) of a subset of these in vivo-expressed genes in clinical specimens yielded the same results as those observed in the murine system. Collectively, our results show that during acute osteomyelitis, S. aureus induced the transcription of genes that mediate metabolic adaptation, immune evasion, and replication. During the chronic phase, however, S. aureus switched its transcriptional response from a proliferative to a persistence mode, probably driven by the severe deficiency in nutrient supplies. Interfering with the survival strategies of S. aureus during chronic infection could lead to more effective treatments. PMID:25538190

  2. [2 cases of osteomyelitis in acute leukemia in the induction phase of treatment].

    PubMed

    De Bernardi, B; Garventa, A; Garrè, M L; Taccone, A; Canale, G; Gandus, S

    1983-01-01

    Whereas children with Acute Leukemia are highly susceptible to infectious complications, the occurrence of acute osteomyelitis is extremely rare in these patients. The authors describe two such cases in children at onset of an acute lymphoblastic and of a myelomonocytic leukemia, respectively. In the former case, the clinical course has been characterized by the progressive involvement of several joints and bones. A citrobacter Freundii was isolated in the synovial fluid of an involved knee. This complication was successfully treated with proper antimicrobic agents and surgical toilet, while the patient was vigorously treated for her leukemia, achieving a complete remission. The latter case developed a right humerus osteomyelitis from an Enterobacter. The patient failed to respond to antibiotics, and his leukemia also turned refractory to antiblastic therapy. The difficulty in the differential diagnosis among the X-graphic aspects of leukemic, inflammatory and degenerative disease of bones are discussed by the authors. Some pathogenetic hypothesis of leukemic osteomyelitis are also presented. PMID:6647082

  3. Quantitative removal of hepatitis B viral antigens from serum by a monoclonal IgM coupled to a biocompatible solid-phase support.

    PubMed Central

    Marciniak, R A; Wands, J R; Bruns, R R; Malchesky, P S; Nose, Y; Haber, E

    1983-01-01

    We covalently linked to regenerated cellulose filters a high-affinity monoclonal IgM produced against epitopes that reside on hepatitis B viral surface antigen (HBsAg). Conditions were established whereby as much as 250 micrograms of anti-HBsAg IgM could be linked to 2-4 mg of regenerated cellulose acetate by using cyanogen bromide and trichloro-s-triazine coupling agents. The immunoreactivity of the monoclonal anti-HBsAg IgM was preserved, and quantitative binding studies with HBsAg suggests that more than one functional binding site on the IgM molecule was operative. The specificity of the monoclonal anti-HBsAg IgM was established by demonstrating that a nonspecific monoclonal IgM (against influenza hemagglutinin), when coupled to the filters under identical conditions, had no effect on removal of HBsAg from serum. Most importantly, the monoclonal anti-HBsAg IgM-coupled filters quantitatively removed low levels of HBsAg from serum; after the third pass through the filter, HBsAg was undetectable in the perfusate. Further, the stability of the covalent bond between the anti-HBsAg IgM and regenerated cellulose acetate was shown by the lack of detectable murine monoclonal anti-HBsAg IgM in filtered serum despite 50 passages through the filter. Thus, we have demonstrated that monoclonal IgM antibodies with predefined specificity, when coupled to a biocompatible solid-phase support, may serve as a high-affinity and specific immunoabsorbant for quantitative removal and recovery of viral antigens from human serum. By using this approach, specific removal and recovery of many other substances from serum or plasma would seem possible. Images PMID:6190181

  4. Evaluation of the prevalence of stress and its phases in acute myocardial infarction in patients active in the labor market

    PubMed Central

    Lucinda, Luciane Boreki; Prosdócimo, Ana Claudia Merchan Giaxa; de Carvalho, Katherine Athayde Teixeira; Francisco, Julio Cesar; Baena, Cristina Pellegrino; Olandoski, Marcia; do Amaral, Vivian Ferreira; Faria, José Rocha; Guarita-Souza, Luiz César

    2015-01-01

    Introduction Acute myocardial infarction is a social health problem of epidemiological relevance, with high levels of morbidity and mortality. Stress is one of the modifiable risk factors that triggers acute myocardial infarction. Stress is a result of a set of physiological reactions, which when exaggerated in intensity or duration can lead to imbalances in one's organism, resulting in vulnerability to diseases. Objective To identify the presence of stress and its phases in hospitalized and active labor market patients with unstable myocardial infarction and observe its correlation with the life of this population with stress. Methods The methodology used was a quantitative, descriptive and transversal research approach conducted with a total of 43 patients, who were still active in the labor market, presenting or not morbidities. Data collection occurred on the fourth day of their hospitalization and patients responded to Lipp's Stress Symptom Inventory for adults. Results Thirty-one patients (72.1%) presented stress and twelve (27.8%) did not. In patients with stress, the identified phases were: alert - one patient (3.2%); resistance -twenty-two patients (71.0%); quasi-exhaustion - six patients (19.4%) and exhaustion - two patients (6.5%). All women researched presented stress. Conclusion The results suggest a high level of stress, especially in the resistance phase, in the male infarcted population, hospitalized and active in the labor market. PMID:25859863

  5. Acute-phase protein α1-antitrypsin--a novel regulator of angiopoietin-like protein 4 transcription and secretion.

    PubMed

    Frenzel, Eileen; Wrenger, Sabine; Immenschuh, Stephan; Koczulla, Rembert; Mahadeva, Ravi; Deeg, H Joachim; Dinarello, Charles A; Welte, Tobias; Marcondes, A Mario Q; Janciauskiene, Sabina

    2014-06-01

    The angiopoietin-like protein 4 (angptl4, also known as peroxisome proliferator-activated receptor [PPAR]γ-induced angiopoietin-related protein) is a multifunctional protein associated with acute-phase response. The mechanisms accounting for the increase in angptl4 expression are largely unknown. This study shows that human α1-antitrypsin (A1AT) upregulates expression and release of angplt4 in human blood adherent mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2- to 174-fold, respectively, relative to controls. In endothelial cells, the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml A1AT (11-fold induction versus controls). In 10 emphysema patients receiving A1AT therapy (Prolastin), plasma angptl4 levels were higher relative to patients without therapy (nanograms per milliliter, mean [95% confidence interval] 127.1 [99.5-154.6] versus 76.8 [54.8-98.8], respectively, p = 0.045) and correlated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pretreated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of HIF-1α, an upregulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute-phase protein A1AT is a physiological regulator of angptl4, another acute-phase protein. PMID:24760148

  6. Effect of Serum Fibrinogen, Total Stent Length, and Type of Acute Coronary Syndrome on 6-Month Major Adverse Cardiovascular Events and Bleeding After Percutaneous Coronary Intervention.

    PubMed

    Mahmud, Ehtisham; Ramsis, Mattheus; Behnamfar, Omid; Enright, Kelly; Huynh, Andrew; Kaushal, Khushboo; Palakodeti, Samhita; Li, Shiqian; Teh, Phildrich; Lin, Felice; Reeves, Ryan; Patel, Mitul; Ang, Lawrence

    2016-05-15

    This study evaluated the relation between baseline fibrinogen and 6-month major adverse cardiovascular events (MACE) and bleeding after percutaneous coronary intervention (PCI). Three hundred eighty-seven subjects (65.6 ± 16.1 years, 69.5% men, 26.9% acute coronary syndrome [ACS]) who underwent PCI with baseline fibrinogen and platelet reactivity (VerifyNow P2Y12 assay, Accumetrics, San Diego, California) measured were enrolled. Fibrinogen (368.8 ± 144.1 vs 316.8 ± 114.3 mg/dl; p = 0.001), total stent length (TSL; 44.5 ± 25.0 vs 32.2 ± 20.1 mm; p <0.001), and ACS presentation (40.6% vs 23.9%; p = 0.005) were independently associated with 6-month MACE rates (17.8%: myocardial infarction 9.8%, rehospitalization for ACS 3.6%, urgent revascularization 3.6%, stroke 0.5%, and death 0.3%). Measures of platelet reactivity were not associated with 6-month MACE. After multivariate analysis, fibrinogen ≥280 mg/dl (odds ratio [OR] 2.60, 95% CI 1.33 to 5.11, p = 0.005), TSL ≥32 mm (OR 3.21, 95% CI 1.82 to 5.64, p <0.001), and ACS presentation (OR 2.58, 95% CI 1.45 to 4.61, p = 0.001) were associated with higher 6-month MACE. In 271 subjects receiving chronic P2Y12 inhibitor therapy, 6-month Thrombolysis In Myocardial Infarction bleeding after PCI was 7.0%, but no difference in fibrinogen level (338.3 ± 109.7 vs 324.3 ± 113.8 mg/dl, p = 0.60) stratified by Thrombolysis In Myocardial Infarction bleeding was observed. In conclusion, elevated serum fibrinogen, ACS presentation, and longer TSL are independently associated with higher 6-month MACE after PCI, whereas no association with on-thienopyridine platelet reactivity and 6-month MACE was observed. Post-PCI bleeding was not associated with lower fibrinogen level. PMID:27040574

  7. Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription.

    PubMed Central

    Qian, X; Samadani, U; Porcella, A; Costa, R H

    1995-01-01

    Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 proteins bind to DNA as monomers through a winged-helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic fork head (fkh) protein. We have previously characterized a strong-affinity HNF-3S site in the transthyretin (TTR) promoter region which is essential for expression in human hepatoma (HepG2) cells. In the current study, we identify an activating protein 1 (AP-1) site which partially overlaps the HNF-3S sequence in the TTR promoter. We show that in HepG2 cells the AP-1 sequence confers 12-O-tetradecanoylphorbol-13-acetate inducibility to the TTR promoter and contributes to normal TTR transcriptional activity. We also demonstrate that the HNF-3 proteins and AP-1 bind independently to the TTR AP-1-HNF-3 site, and cotransfection experiments suggest that they do not cooperate to activate an AP-1-HNF-3 reporter construct. In addition, 12-O-tetradecanoylphorbol-13-acetate exposure of HepG2 cells results in a reciprocal decrease in HNF-3 alpha and -3 gamma expression which may facilitate interaction of AP-1 with the TTR AP-1-HNF-3 site. In order to explore the role of HNF-3 in the liver, we have examined expression patterns of TTR and HNF-3 during the acute-phase response and liver regeneration. Partial hepatectomy produced minimal fluctuation in HNF-3 and TTR expression, suggesting that HNF-3 expression is not influenced by proliferative signals induced during liver regeneration. In acute-phase livers, we observed a dramatic reduction in HNF-3 alpha expression which correlates with a decrease in the expression of its target gene, the TTR gene. Furthermore, consistent with previous studies, the acute-phase livers are induced for c-jun but not c-fos expression. We propose that the reduction in TTR gene expression during the acute phase is likely due

  8. Genetic effects on acute phase protein response to the stresses of weaning and transportation in beef calves.

    PubMed

    Qiu, X; Arthington, J D; Riley, D G; Chase, C C; Phillips, W A; Coleman, S W; Olson, T A

    2007-10-01

    The objective herein was to estimate heterosis and breed effects in purebred and crossbred Romosinuano, Brahman, and Angus calves on acute phase protein response to weaning and transportation. Calves (n = 1,032) were weaned in September of 2002, 2003, and 2004 at approximately 7 mo of age. Approximately 28 d after weaning, steer calves (n = 482) were transported 1,800 km (20 h) to Oklahoma. Concentrations of 3 acute phase proteins (ceruloplasmin, fibrinogen, and haptoglobin) were measured in blood samples. Calves (steers and heifers) were sampled at weaning, and 24 and 72 h postweaning. For separate analyses, steers sent to Oklahoma were sampled before shipment, upon arrival, and 24 and 72 h after arrival. Combinations of the following fixed effects were investigated: sire breed, dam breed, sampling time, birth location, calf sex (weaning only), year, cow age, and interactions. Effects of special interest were sire breed x dam breed as an indication of breed group of calf, and the interaction of sire and dam breeds with sampling time. Weaning age and BW were investigated as linear and quadratic covariates. Sire of calf within sire breed was a random term. The correlation structure of repeated measures was determined by comparison of information criterion values for different structures within each analysis. In general, plasma acute phase protein concentrations in weaned calves increased with sampling time. Concentrations in the transported steers increased through sampling at 24 h after arrival, and were lower at 72 h. Significant estimates of heterosis were detected for Brahman-Angus haptoglobin concentrations at weaning (0.38 +/- 0.14 mg/dL x 100; 44%), and for Romosinuano-Angus fibrinogen concentrations at weaning (11.4 +/- 5.5 mg/dL; 10%) and in transported steers (22.5 +/- 8.4 mg/dL; 20%). The direct effect of Romosinuano was to increase (P <0.004) ceruloplasmin concentrations of weaned calves (4.1 +/- 0.9 mg/dL) and of transported steers (3.9 +/- 1.3 mg

  9. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    PubMed Central

    2012-01-01

    Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

  10. Phase-based metamorphosis of diffusion lesion in relation to perfusion values in acute ischemic stroke.

    PubMed

    Rekik, Islem; Allassonnière, Stéphanie; Luby, Marie; Carpenter, Trevor K; Wardlaw, Joanna M

    2015-01-01

    Examining the dynamics of stroke ischemia is limited by the standard use of 2D-volume or voxel-based analysis techniques. Recently developed spatiotemporal models such as the 4D metamorphosis model showed promise for capturing ischemia dynamics. We used a 4D metamorphosis model to evaluate acute ischemic stroke lesion morphology from the acute diffusion-weighted imaging (DWI) to final T2-weighted imaging (T2-w). In 20 representative patients, we metamorphosed the acute lesion to subacute lesion to final infarct. From the DWI lesion deformation maps we identified dynamic lesion areas and examined their association with perfusion values inside and around the lesion edges, blinded to reperfusion status. We then tested the model in ten independent patients from the STroke Imaging Repository (STIR). Perfusion values varied widely between and within patients, and were similar in contracting and expanding DWI areas in many patients in both datasets. In 25% of patients, the perfusion values were higher in DWI-contracting than DWI-expanding areas. A similar wide range of perfusion values and ongoing expansion and contraction of the DWI lesion were seen subacutely. There was more DWI contraction and less expansion in patients who received thrombolysis, although with widely ranging perfusion values that did not differ. 4D metamorphosis modeling shows promise as a method to improve use of multimodal imaging to understand the evolution of acute ischemic tissue towards its fate. PMID:26288755

  11. The Usefulness of the TOAST Classification and Prognostic Significance of Pyramidal Symptoms During the Acute Phase of Cerebellar Ischemic Stroke.

    PubMed

    Dziadkowiak, Edyta; Chojdak-Łukasiewicz, Justyna; Guziński, Maciej; Noga, Leszek; Paradowski, Bogusław

    2016-04-01

    Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p = 0.00094) and with pyramidal signs (p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis. PMID:26041073

  12. The Incidence and Clinical Characteristics of Acute Serum Creatinine Elevation more than 1.5 mg/dL among the Patients Treated with Tenofovir/Emtricitabine-containing HAART Regimens

    PubMed Central

    Kim, Myung Hi; Park, Jung Hwa; Jung, Hye Jin; Lee, Hye Jin; Lee, Jong Myung; Kim, Sujeong

    2015-01-01

    Background The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been the first choice nucleoside reverse transcriptase inhibitor (NRTI) according to many reliable antiretroviral treatment (ART) guidelines because of its high efficacy. However, TDF-related renal toxicity reported in Western countries is a challenging issue regarding clinical use. We conducted this study to evaluate the incidence and characteristics of an acute increase in serum creatinine (Cr) level > 1.5 mg/dL among TDF/FTC-based highly active antiretroviral treatment (HAART)-treated patients. Materials and Methods We retrospectively reviewed the medical records of 205 HIV-infected patients treated with TDF/FTC-containing regimens between 1 February 2010 and 30 April 2014. Three groups of TDF/FTC + ritonavir-boosted protease inhibitor (PI/r), TDF/FTC + non-nucleoside reverse transcriptase inhibitor (NNRTI), and TDF/FTC + integrase strand transfer inhibitor (INSTI), and three PI/r subgroups of TDF/FTC + lopinavir (LPV)/r, TDF/FTC + atazanavir (ATV)/r, TDF/FTC + darunavir (DRV)/r were evaluated. Results A total 136 patients (91 in the TDF/FTC + PI/r group, 20 in the TDF/FTC + NNRTI group and 25 in the TDF/FTC + INSTI group) were included in the statistical analysis. Four cases (4.9%; all in the TDF/FTC + PI/r group) among 136 patients showed an acute increase in serum Cr more than 1.5 mg/dL, so the overall incidence was 2.8 cases per 100 patient-years. One case was a patient treated with TDF/FTC + LPV/r, and the others were treated with TDF/FTC + ATV/r. No case of an acute increase in serum Cr was observed in the TDF/FTC + DRV/r group. The incidence of serum Cr increase more than 1.5 mg/dL in TDF/FTC + PI/r group was 4.0 cases per 100 patient-years. Conclusion Although only a small number of patients were evaluated retrospectively from a single center, the TDF/FTC + PI/r regimen may have been related with relatively higher tendency of increment of serum Cr level. These

  13. Relation between the serum albumin level and nutrition supply in patients with pressure ulcers: retrospective study in an acute care setting.

    PubMed

    Sugino, Hirotaka; Hashimoto, Ichiro; Tanaka, Yuka; Ishida, Soshi; Abe, Yoshiro; Nakanishi, Hideki

    2014-01-01

    This retrospective study examined the validity of the commonly used serum albumin level as an indicator of nutrition status of patients with pressure ulcer(s), particularly because the serum albumin level is affected by various factors and may not be specific to malnutrition. Specifically, we investigated whether nutrition supply or inflammation affects the serum albumin level in 82 patients with pressure ulcers(s) (29 in whom pressure ulcer was present upon admission and 53 in whom pressure ulcer developed after hospital admission). Serum albumin levels, blood test including C-reactive protein (CRP) levels and blood count, caloric intake, and depth and healing of pressure ulcers were compared between various subgroups of patients. Serum albumin levels correlated with red blood cell counts and hemoglobin and CRP levels but not with caloric intake. The correlation with CRP before and after several weeks of pressure ulcer treatment was negative. The serum albumin level upon admission was higher in patients in whom the ulcer healed than in those in whom it did not heal as well as in patients who were discharged than in those who died in the hospital. The serum albumin level appears to reflect inflammation, wound healing, and disease severity rather than nutrition supply in patients with pressure ulcer. J. Med. Invest. 61: 15-21, February, 2014. PMID:24705743

  14. Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke: Results of a Prematurely Terminated Randomized Clinical Trial

    PubMed Central

    Haley, E. Clarke; Thompson, John L.P.; Grotta, James C.; Lyden, Patrick D.; Hemmen, Thomas G.; Brown, Devin L.; Fanale, Christopher; Libman, Richard; Kwiatkowski, Thomas G.; Llinas, Rafael H.; Levine, Steven R.; Johnston, Karen C.; Buchsbaum, Richard; Levy, Gilberto; Levin, Bruce

    2010-01-01

    Background: Intravenous alteplase (rt-PA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to a) choose a best dose of tenecteplase to carry forward, and b) to provide evidence for either promise or futility of further testing of tenecteplase versus rt-PA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rt-PA. Methods: The trial began as a small, multi-center, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rt-PA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24 hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage (ICH) to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rt-PA could be compared by 3 month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4 mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3 month outcomes between the remaining tenecteplase groups and rt-PA. Symptomatic ICH rates were highest in the

  15. The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

    PubMed Central

    Johnstone, Victoria P.A.; Shultz, Sandy R.; Yan, Edwin B.; O'Brien, Terence J.

    2014-01-01

    Abstract The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes. PMID:24927383

  16. Time course of acute-phase response induced by Tityus serrulatus venom and TsTX-I in mice.

    PubMed

    Pessini, Andréa C; de Souza, Ana M; Faccioli, Lúcia H; Gregório, Zita M O; Arantes, Eliane C

    2003-05-01

    Animal venom can induce systemic alterations similar to those observed in acute-phase inflammatory response. In the present study, we report the systemic (circulatory) and local (peritoneal cavity) effects induced by Tityus serrulatus venom and its major toxin TsTX-I (Ts1) in mice over various time periods. Both the venom and TsTX-I elicited quite similar responses in most assays. Responses included reduction of albumin, increased C-reactive protein, IL-6, IL-1alpha and TNF-alpha. Local and systemic leucocytosis, with a predominance of polymorphonuclear cells, was also observed. These effects show that a systemic inflammation-like syndrome is triggered during the severe envenomation caused by the T. serrulatus sting. The initial increases of albumin and total protein were probably consequences of the dehydration that occurs at the beginning of envenomation. Time-course analysis of these effects shows that responses are most pronounced on the first day after poisoning. However, leucocytosis and changes in acute-phase protein concentrations can be observed up to 7 days after envenomation. PMID:12757745

  17. [Cerebroprotective effect of 3-oxypyridine and succinic acid derivatives in acute phase of alloxan-induced diabetes mellitus in rats].

    PubMed

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    The effects of original domestic derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin, and mexidol) on cellular composition of cortical and diencephalic structures in rat brain were studied in parallel with monitoring of behavioral, conditional learning, and metabolic disorders in acute phase of alloxan-induced diabetes in rats. The efficiency of 3-oxypyridine derivatives was compared to the results of alpha-lipoic acid administration. Single administration of emoxipine, reamberin, and mexidol in optimal doses prevented lipofuscin deposition in CA1 field neurocytes in hippocampus and/or increased the amount of terminally differentiated cells ofneuroectodermal lineage (oligodendrocytes, pyramid and basket cells) in this zone ofpaleocortex. Concurrently conditional learning capacity in morbid animals was restored. The cerebroprotective and nootropic effects of emoxipine and reamberin were associated with increased exploration motivation in the open field and were independent of their effects on carbohydrate and lipid metabolism dysfunction. On the contrary, the neuroprotective and nootropic effects of mexidol were associated with additional inhibition of morbid rat activity in the open field and a decrease in the level of circulating products of lipid peroxidation. It is established that 3-oxypyridine and succinic acid derivatives significantly exceed alpha-lipoic acid in terms of neuroprotective effects but exhibit significantly lower hypolipdemic activity in acute phase of alloxan diabetes. PMID:21809693

  18. Circulating Cytokine Profiles and Their Relationships with Autoantibodies, Acute Phase Reactants, and Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Meyer, Pieter W. A.; Hodkinson, Bridget; Ally, Mahmood; Musenge, Eustasius; Wadee, Ahmed A.; Fickl, Heidi; Tikly, Mohammed; Anderson, Ronald

    2010-01-01

    Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001), and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants, CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were significantly correlated (P < .04–.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA. PMID:21437211

  19. Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study.

    PubMed

    Wang, Kevin K W; Yang, Zhihui; Yue, John K; Zhang, Zhiqun; Winkler, Ethan A; Puccio, Ava M; Diaz-Arrastia, Ramon; Lingsma, Hester F; Yuh, Esther L; Mukherjee, Pratik; Valadka, Alex B; Gordon, Wayne A; Okonkwo, David O; Manley, Geoffrey T; Cooper, Shelly R; Dams-O'Connor, Kristen; Hricik, Allison J; Inoue, Tomoo; Maas, Andrew I R; Menon, David K; Schnyer, David M; Sinha, Tuhin K; Vassar, Mary J

    2016-07-01

    We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean ± standard error: 9.11 ± 1.42; n = 43) than healthy controls (2.90 ± 0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 ± 0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 ± 1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 ± 2.82; n = 21) than healthy controls (p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between post-injury brain and patient-specific autoimmune responses across acute and chronic settings after TBI. PMID:26560343

  20. Chronic Spontaneous Urticaria Is Characterized by Lower Serum Advanced Glycation End-Products

    PubMed Central

    Grzanka, Alicja; Damasiewicz-Bodzek, Aleksandra; Machura, Edyta; Szumska, Magdalena; Tyrpień-Golder, Krystyna; Mazur, Bogdan; Kasperska-Zajac, Alicja

    2014-01-01

    Background. Chronic spontaneous urticaria (CSU) is associated with activation of acute phase response. On the other hand, it is known that systemic inflammation may lead to increased formation of advanced glycation end-products (AGEs), associated with pathogenesis of various diseases. Aim. We aim to test whether chronic inflammation manifested by activated acute phase response may provide a mechanism for increased serum AGEs concentration in CSU. Methods. Concentrations of AGEs were measured spectrofluorimetrically in serum of CSU patients and the healthy subjects. Results. Serum AGEs and albumin concentrations in CSU patients were significantly lower as compared with the healthy subjects. Serum CRP concentration was significantly higher in patients with CSU than in the controls. Significant positive correlation was observed between AGEs and albumin concentrations in the subjects. Conclusions. CSU is not associated with increased circulating AGEs concentrations, despite the enhanced systemic inflammatory response. Paradoxical decrease of serum AGEs concentrations is probably a reflection of lower concentration of “negative acute phase proteins” such as albumin. PMID:25180195

  1. A selected reaction monitoring-based analysis of acute phase proteins in interstitial fluids from experimental equine wounds healing by secondary intention.

    PubMed

    Bundgaard, Louise; Bendixen, Emøke; Sørensen, Mette Aa; Harman, Victoria M; Beynon, Robert J; Petersen, Lars J; Jacobsen, Stine

    2016-05-01

    In horses, pathological healing with formation of exuberant granulation tissue (EGT) is a particular problem in limb wounds, whereas body wounds tend to heal without complications. Chronic inflammation has been proposed to be central to the pathogenesis of EGT. This study aimed to investigate levels of inflammatory acute phase proteins (APPs) in interstitial fluid from wounds in horses. A novel approach for absolute quantification of proteins, selected reaction monitoring (SRM)-based mass spectrometry in combination with a quantification concatamer (QconCAT), was used for the quantification of five established equine APPs (fibrinogen, serum amyloid A, ceruloplasmin, haptoglobin, and plasminogen) and three proposed equine APPs (prothrombin, α-2-macroglobulin, and α-1-antitrypsin). Wound interstitial fluid was recovered by large pore microdialysis from experimental body and limb wounds from five horses at days 1, 2, 7, and 14 after wounding and healing without (body) and with (limb) the formation of EGT. The QconCAT included proteotypic peptides representing each of the protein targets and was used to direct the design of a gene, which was expressed in Escherichia coli in a media supplemented with stable isotopes for metabolically labeling of standard peptides. Co-analysis of wound interstitial fluid samples with the stable isotope-labeled QconCAT tryptic peptides in known amounts enabled quantification of the APPs in absolute terms. The concentrations of fibrinogen, haptoglobin, ceruloplasmin, prothrombin, and α-1-antitrypsin in dialysate from limb wounds were significantly higher than in dialysate from body wounds. This is the first report of simultaneous analysis of a panel of APPs using the QconCAT-SRM technology. The microdialysis technique in combination with the QconCAT-SRM-based approach proved useful for quantification of the investigated proteins in the wound interstitial fluid, and the results indicated that there is a state of sustained inflammation in

  2. Optimization of the determination of polybrominated diphenyl ethers in human serum using solid-phase extraction and gas chromatography-electron capture negative ionization mass spectrometry.

    PubMed

    Covaci, Adrian; Voorspoels, Stefan

    2005-12-01

    A simple, rapid, sensitive and reproducible method based on solid-phase extraction (SPE) and acidified silica clean-up was developed for the measurement of 12 polybrominated diphenyl ethers (PBDEs), including BDE 209, and 2,2',4,4',5,5'-hexabromobiphenyl (BB 153) in human serum. Several solid-phase sorbents (Empore C(18), Isolute Phenyl, Isolute ENV+ and OASIS HLB) were tested and it was found that OASIStrade mark HLB (500 mg) gives the highest absolute recoveries (between 64% and 95%, R.S.D.<17%, n=3) for all tested analytes and internal standards. Removal of co-extracted biogenic materials was performed using a 6 ml disposable cartridge containing (from bottom to top) silica impregnated with sulphuric acid, activated silica and anhydrous sodium sulphate. PBDEs and BB 153 were quantified using a gas chromatograph coupled with a mass spectrometer (MS) operated in electron-capture negative ionization mode. The method limits of quantification (LOQ) ranged between 0.2 and 25 pg/ml serum (0.1 and 4 ng/g lipid weight). LOQs were dependent on the analyte levels in procedural blanks which resulted in the highest LOQs for PBDE congeners found in higher concentrations in blanks (e.g. BDE 47, 99 and 209). The use of OASIS HLB SPE cartridge allowed a good method repeatability (within- and between-day precision<12% for all congeners, except for BDE 209<17%, n=3). The method was applied to serum samples from a random Belgian population. The obtained results were within the range of PBDE levels in other non-exposed population from Europe. PMID:16203180

  3. Supervised Phase II Cardiac Exercise Therapy Shortens the Recovery of Exercise Capacity in Patients with Acute Myocardial Infarction

    PubMed Central

    Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Wu, Yu-Zu; Chen, Tung-Wei; Huang, Chien-Hui

    2014-01-01

    [Purpose] To investigate the effects of Phase II cardiac exercise therapy (CET) on exercise capacity and changes in coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Subjects] Thirty male subjects with AMI were divided into an experimental group (EG) and a control group (CG). Another 30 age-matched subjects with patent coronary arteries served as a normal-control group (NCG). [Methods] Subjects in EG (n=20) trained using a stationary bicycle for 30 min at their target heart rate twice a week for 8 weeks. Exercise capacity was defined as the maximal metabolic equivalents (METs) that subjects reached during the symptom-limited maximal exercise test. HR, BP and RPP were recorded. Subjects in EG and CG received exercise tests and screening for CRFs at the beginning of, end of, and 3 months after Phase II CET, while subjects in NCG participated only in the 1st test. [Results] METs of CG did not improve until the 3rd test, while RPP at the 2nd test showed a significant increase. However, EG showed increased METs at the 2nd test without increase of RPP, and increased their high density lipoprotein cholesterol (HDL-C) during the follow-up period between the 2nd and 3rd tests. [Conclusion] Phase II CET shortens the recovery time of exercise capacity, helps to maintain the gained exercise capacity and increases HDL-C in phase III. PMID:25276046

  4. Supervised Phase II Cardiac Exercise Therapy Shortens the Recovery of Exercise Capacity in Patients with Acute Myocardial Infarction.

    PubMed

    Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Wu, Yu-Zu; Chen, Tung-Wei; Huang, Chien-Hui

    2014-09-01

    [Purpose] To investigate the effects of Phase II cardiac exercise therapy (CET) on exercise capacity and changes in coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Subjects] Thirty male subjects with AMI were divided into an experimental group (EG) and a control group (CG). Another 30 age-matched subjects with patent coronary arteries served as a normal-control group (NCG). [Methods] Subjects in EG (n=20) trained using a stationary bicycle for 30 min at their target heart rate twice a week for 8 weeks. Exercise capacity was defined as the maximal metabolic equivalents (METs) that subjects reached during the symptom-limited maximal exercise test. HR, BP and RPP were recorded. Subjects in EG and CG received exercise tests and screening for CRFs at the beginning of, end of, and 3 months after Phase II CET, while subjects in NCG participated only in the 1st test. [Results] METs of CG did not improve until the 3rd test, while RPP at the 2nd test showed a significant increase. However, EG showed increased METs at the 2nd test without increase of RPP, and increased their high density lipoprotein cholesterol (HDL-C) during the follow-up period between the 2nd and 3rd tests. [Conclusion] Phase II CET shortens the recovery time of exercise capacity, helps to maintain the gained exercise capacity and increases HDL-C in phase III. PMID:25276046

  5. High-performance liquid chromatographic determination of ursodeoxycholic acid after solid phase extraction of blood serum and detection-oriented derivatization.

    PubMed

    Nobilis, M; Pour, M; Kunes, J; Kopecký, J; Kvĕtina, J; Svoboda, Z; Sládková, K; Vortel, J

    2001-03-01

    Ursodeoxycholic acid (3 alpha,7 beta-dihydroxy-5 beta-cholanoic acid, UDCA) is a therapeutically applicable bile acid widely used for the dissolution of cholesterol-rich gallstones and in the treatment of chronic liver diseases associated with cholestasis. UDCA is more hydrophilic and less toxic than another therapeutically valuable bile acid, chenodeoxycholic acid (CDCA), the 7 alpha-epimer of UDCA. Procedures for sample preparation and HPLC determination of UDCA in blood serum were developed and validated. A higher homologue of UDCA containing an additional methylene group in the side chain was synthetized and used as an internal standard (IS). Serum samples with IS were diluted with a buffer (pH=7). The bile acids and IS were captured using solid phase extraction (C18 cartridges). The carboxylic grou