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Sample records for fibrinogen metabolic responses

  1. Study of radioactive fibrinogen metabolism in renal allotransplantation

    Akiyama, Takahiro; Nagai, Nobuo; Kaneko, Shigeo; Matsuura, Takeshi; Iguchi, Masanori

    1979-01-01

    Turn over administrated radioactive fibrinogen and uptake to renal allograft were studied in 9 cases of renal allotransplanted patients. In patients with acute rejection crisis biological half-time (T 1/2) of 131 I-fibrinogen were shortened and allograft/heart counts ratio of 125 I-fibrinogen were elevated up to 125 - 140 percent at 24 - 48 hours after administration; these parameters seemed to be useful in aid of diagnosis of acute rejection. It is suggested that deposition of fibrinogen into allograft and increased turn over of plasma fibrinogen occurred in acute rejection. (author)

  2. Carotid intima-media thickness and plasma fibrinogen among subjects with metabolic syndrome: Isfahan cohort study

    Zahra Bayanfar

    2014-09-01

    Full Text Available BACKGROUND: The role of plasma fibrinogen, a key regulator of inflammation processes and increased carotid intima-media thickness (cIMT to predict metabolic syndrome (MetS is currently under investigation. We assessed differences in the indicators of cIMT and also plasma fibrinogen level between MetS and non-MetS subjects. We also assessed the role of these two parameters for independently relationship with MetS state. METHODS: The subjects in this cross-sectional survey were population-based samples of 93 men and women aged ≥ 35 years and over who were selected from the Isfahan cohort study, Isfahan, Iran. Fibrinogen was measured by the clotting assay of Clauss. Ultrasound studies of the carotid artery were performed to measure cIMT. MetS defined based on the National Cholesterol Education Program’s Adult Treatment Panel III. RESULTS: The mean level of plasma fibrinogen was not different in the two groups with and without MetS (240.10 ± 27.80 vs. 242.56 ± 35.82, P = 0.714, but the mean of cIMT was considerably higher in MetS group than in non-MetS group (0.85 ± 0.06 mm vs. 0.66 ± 0.09 mm, P < 0.001. Using a multivariable logistic regression model, high cIMT could effectively predict MetS state with the presence of different components of MetS (odds ratio = 17.544, 95% confidence interval: 2.151-142.860, P = 0.008. The optimal cutoff point of cIMT for discriminating these two clinical states was 0.6 mm yielding a sensitivity of 61.5% and a specificity of 59.6%. CONCLUSION: Individuals with MetS demonstrated increased cIMT values compared with those without MetS. However, high plasma fibrinogen level may not be associated with MetS state.   Keywords: Metabolic Syndrome, Carotid Intima-Media Thickness, Fibrinogen, Prediction 

  3. Rapidly produced /sup 125/I labelled autologous fibrinogen: in vitro properties and preliminary metabolic studies in man

    Hawker, R J; Hawker, L M [Birmingham Univ. (UK)

    1976-06-01

    The properties of fibrinogen extracted by a precipitation method using glycine at ambient temperatures near neutral pH are described. The simple and reproducible method gave a 73% yield of high purity plasminogen-free fibrinogen in 45 minutes from small volumes of plasma. The protein extract was labelled with /sup 125/I using chloramine-T under conditions optimal for fibrinogen stability. The extraction procedure, radio-iodination, desalting, and sterilization take only 70 minutes for completion from the time donor blood is received in the laboratory. The methods, using a specially developed extraction vessel and desalting/sterilizing column, can be used in a small hospital laboratory. Autologous fibrinogen can thus be extracted from patients' blood, eliminating the risk of transmitting hepatitis when it is re-administered. The autologous material, which is 97% clottable and contains less than 0.05% free iodide, is being routinely used as a diagnostic tool in the detection of deep vein thrombosis. The high purity of the preparation facilitates metabolic studies and in vitro experimental work. In vivo results showed a mean half-life in three normal volunteers of 3.95 days and a catabolic rate of 25.23% per day with the extravascular space estimated as 24.86%. In 30 surgical patients an expected reduced half-life in plasma was determined with a mean of 3.1 days.

  4. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

    Zhao, Jun; Zheng, Shuang; Zhou, Qiyin; Li, Heming; Liu, Yunpeng; Qu, Xiujuan; Zhao, Mingfang; Jin, Bo; Yu, Ping; Hu, Xuejun; Teng, Yuee; Zhang, Jingdong; Luo, Ying; Zhang, Lingyun

    2012-01-01

    Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. This study showed that the reduction in plasma fibrinogen levels

  5. Fibrinogen and fibrin.

    Weisel, John W

    2005-01-01

    , thrombospondin, von Willebrand factor, fibulin, fibroblast growth factor-2, vascular endothelial growth factor, and interleukin-1. Studies of naturally occurring dysfibrinogenemias and variant molecules have increased our understanding of fibrinogen's functions. Fibrinogen binds to activated alphaIIbbeta3 integrin on the platelet surface, forming bridges responsible for platelet aggregation in hemostasis, and also has important adhesive and inflammatory functions through specific interactions with other cells. Fibrinogen-like domains originated early in evolution, and it is likely that their specific and tightly controlled intermolecular interactions are involved in other aspects of cellular function and developmental biology.

  6. Fibrinogen monitor

    1980-01-01

    Apparatus is described for use in detecting the formation of blood clots in a patient who has previously been injected with a tracer quantity of radioactive fibrinogen. It consists of a scintillation detector, associated electronics for pulse processing and a digital display for the operator as well as a punched paper-tape for permanent record. The detector measures the radioactive count rate along the patient's leg over a given interval and compares this with a reference value. Higher count rate events which are deemed to be statistically significant, indicate thrombosis. Lower than average count rates usually indicate mis-alignment of the detector and patient's leg and warning of such is given to the operator. Compared to previous instruments, the present apparatus is easier to use and is also more comfortable for the patient. (UK)

  7. Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group) trial

    Guida, Michele; Ravaioli, Alessandra; Sileni, Vanna Chiarion; Romanini, Antonella; Labianca, Roberto; Freschi, Antonio; Brugnara, Salvatore; Casamassima, Addolorata; Lorusso, Vito; Nanni, Oriana; Ridolfi, Ruggero

    2003-01-01

    Purpose To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM) in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT) vs bioCT. Methods A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine) or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular α-IFN-2b). Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP), lactate dehydrogenase (LDH), erytrosedimentation rate (ESR), and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site) were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2%) and OS (11 Mo vs 9.5 Mo), all analyses are stratified by treatment arm. Results In univariate analysis, higher value of lymphocytes percentage (P < .0001), lower value of total leucocytes (P=.005), CRP (P=.003), LHD (P < .0001), ESR (P < .027), fibrinogen (P < .0001), and no liver disease were strongly related to a better survival. In a multivariate analysis, using the Cox proportional hazards model, only fibrinogen (P=.004), LDH (P=.009) and liver disease (P=.04) were found to have an independent role on clinical outcome in metastatic melanoma patients. Conclusion Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used. PMID:14690541

  8. Interindividual variation in the response by fibrinogen, C-reactive protein and interleukin-6 to yellow fever vaccination

    Verschuur, M.; Beek, M.T. van der; Tak, H.S.; Visser, L.G.; Maat, M.P.M. de

    2004-01-01

    The acute phase reaction is important in many disease processes. Habitual levels of the acute phase proteins fibrinogen, C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with an increased risk of cardiovascular disease, but the dynamic variation of plasma levels of acute phase

  9. Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group trial

    Casamassima Addolorata

    2003-12-01

    Full Text Available Abstract Purpose To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT vs bioCT. Methods A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular α-IFN-2b. Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP, lactate dehydrogenase (LDH, erytrosedimentation rate (ESR, and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2% and OS (11 Mo vs 9.5 Mo, all analyses are stratified by treatment arm. Results In univariate analysis, higher value of lymphocytes percentage (P Conclusion Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used.

  10. Competitions between fibrinogen with its degradation products for interactions with the platelet-fibrinogen receptor

    Thorsen, L.I.; Brosstad, F.; Gogstad, G.; Sletten, K.; Solum, N.O.

    1986-01-01

    Direct binding of 125 -I-labelled plasmic and CNBr-derived fibrin (ogen) fragments (pre-X, X, Y, D, Degta, Efg, E1, N-DSK, N-dsk) to gel-filtered platelets was compared to their ability to support or inhibit ADP-induced aggregation, and to compete with fibrinogen for binding to ADP-stimulated platelets. Pre-X was the only fragment that supported aggregation. All fragments tested except for E derived from fibrinogen (Efg) and Degta bound specifically to the platelets and inhibited ADP-induced aggregation in the presence of fibrinogen. Competitive binding studies with fibrinogen and fragments labelled with different isotopes of iodine, or inhibition of binding of labelled fibrinogen with unlabelled fragments showed that all of the fragments except Efg and Degta were able to compete with fibrinogen for binding. When simultaneous binding of N-dsk and fibrinogen was studied, an increased binding of both ligands was observed probably due to complex formation. The results fully agree with previous findings of binding to immunoprecipitated glycoprotein IIb-IIIa after crossed immunoelectrophoresis. We conclude that the fibrinogen molecule contains at least six sequences responsible for platelet interaction, two in the E domain and two in each of the C-terminal parts of the fibrinogen molecule

  11. Human plasma fibrinogen adsorption and platelet adhesion to polystyrene.

    Tsai, W B; Grunkemeier, J M; Horbett, T A

    1999-02-01

    The purpose of this study was to further investigate the role of fibrinogen adsorbed from plasma in mediating platelet adhesion to polymeric biomaterials. Polystyrene was used as a model hydrophobic polymer; i.e., we expected that the role of fibrinogen in platelet adhesion to polystyrene would be representative of other hydrophobic polymers. Platelet adhesion was compared to both the amount and conformation of adsorbed fibrinogen. The strategy was to compare platelet adhesion to surfaces preadsorbed with normal, afibrinogenemic, and fibrinogen-replenished afibrinogenemic plasmas. Platelet adhesion was determined by the lactate dehydrogenase (LDH) method, which was found to be closely correlated with adhesion of 111In-labeled platelets. Fibrinogen adsorption from afibrinogenemic plasma to polystyrene (Immulon I(R)) was low and polystyrene preadsorbed with fibrinogen-replenished afibrinogenemic plasma. Addition of even small, subnormal concentrations of fibrinogen to afibrinogenemic plasma greatly increased platelet adhesion. In addition, surface-bound fibrinogen's ability to mediate platelet adhesion was different, depending on the plasma concentration from which fibrinogen was adsorbed. These differences correlated with changes in the binding of a monoclonal antibody that binds to the Aalpha chain RGDS (572-575), suggesting alteration in the conformation or orientation of the adsorbed fibrinogen. Platelet adhesion to polystyrene preadsorbed with blood plasma thus appears to be a strongly bivariate function of adsorbed fibrinogen, responsive to both low amounts and altered states of the adsorbed molecule. Copyright 1999 John Wiley & Sons, Inc.

  12. Fibrinogen concentrate in bleeding patients

    Wikkelsø, Anne; Lunde, Jens; Johansen, Mathias

    2013-01-01

    Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic...

  13. Serum bilirubin levels are inversely associated with PAI-1 and fibrinogen in Korean subjects.

    Cho, Hyun Sun; Lee, Sung Won; Kim, Eun Sook; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun

    2016-01-01

    Oxidative stress may contribute to atherosclerosis and increased activation of the coagulation pathway. Bilirubin may reduce activation of the hemostatic system to inhibit oxidative stress, which would explain its cardioprotective properties shown in many epidemiological studies. This study investigated the association of serum bilirubin with fibrinogen and plasminogen activator inhibitor-1 (PAI-1), respectively. A cross-sectional analysis was performed on 968 subjects (mean age, 56.0 ± 11.2 years; 61.1% men) undergoing a general health checkup. Serum biochemistry was analyzed including bilirubin subtypes, insulin resistance (using homeostasis model of assessment [HOMA]), C-reactive protein (CRP), fibrinogen, and PAI-1. Compared with subjects with a total bilirubin (TB) concentration of 17.1 μmol/L had a smaller waist circumference, a lower triglyceride level, a lower prevalence of metabolic syndrome, and decreased HOMA-IR and CRP levels. Correlation analysis revealed linear relationships of fibrinogen with TB and direct bilirubin (DB), whereas PAI-1 was correlated with DB. After adjustment for confounding factors, bilirubin levels were inversely associated with fibrinogen and PAI-1 levels, respectively. Multivariate regression models showed a negative linear relationship between all types of bilirubin and fibrinogen, whereas there was a significant linear relationship between PAI-1 and DB. High bilirubin concentrations were independently associated with low levels of fibrinogen and PAI-1, respectively. The association between TB and PAI-1 was confined to the highest TB concentration category whereas DB showed a linear association with PAI-1. Bilirubin may protect against the development of atherothrombosis by reducing the hemostatic response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Selected Metabolic Responses to Skateboarding

    Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

    2011-01-01

    Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

  15. Substrate metabolism in the metabolic response to injury

    Romijn, J. A.

    2000-01-01

    In healthy subjects the metabolic response to starvation invokes regulatory mechanisms aimed at conservation of protein mass. This response is characterized by a decrease in energy expenditure and a progressive decrease in urinary N excretion. Many non-endocrine diseases induce anorexia and a

  16. Fibrinogen in trauma, an evaluation of thrombelastography and rotational thromboelastometry fibrinogen assays

    Meyer, Martin A S; Ostrowski, Sisse R; Sørensen, Anne Marie

    2015-01-01

    BACKGROUND: Identifying hypofibrinogenemia in trauma is important. The optimal method of fibrinogen determination is unknown. We therefore evaluated fibrinogen levels determined by two whole blood viscoelastic hemostatic assays, thrombelastography functional fibrinogen (FF) and rotational thrombo...

  17. Conformational changes of fibrinogen in dispersed carbon nanotubes

    Park SJ

    2012-08-01

    Full Text Available Sung Jean Park,1 Dongwoo Khang21College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, South Korea; 2School of Nano and Advanced Materials Science Engineering and Center for PRC and RIGET, Gyeongsang National University, Jinju, South KoreaAbstract: The conformational changes of plasma protein structures in response to carbon nanotubes are critical for determining the nanotoxicity and blood coagulation effects of carbon nanotubes. In this study, we identified that the functional intensity of carboxyl groups on carbon nanotubes, which correspond to the water dispersity or hydrophilicity of carbon nanotubes, can induce conformational changes in the fibrinogen domains. Also, elevation of carbon nanotube density can alter the secondary structures (ie, helices and beta sheets of fibrinogen. Furthermore, fibrinogen that had been in contact with the nanoparticle material demonstrated a different pattern of heat denaturation compared with free fibrinogen as a result of a variation in hydrophilicity and concentration of carbon nanotubes. Considering the importance of interactions between carbon nanotubes and plasma proteins in the drug delivery system, this study elucidated the correlation between nanoscale physiochemical material properties of carbon nanotubes and associated structural changes in fibrinogen.Keywords: carbon nanotubes, fibrinogen, nanotoxicity, conformational change, denaturation

  18. Metabolic Responses to Weight Lifting

    Arnold Nelson

    2017-04-01

    Full Text Available Editor's Note, The ability to lift heavy loads while performing multiple repetitions is not only highly correlated with muscle mass or the total number actomyosin interactions, but also metabolic functions that includes substrate concentrations and by-product removal.  Muscles use adenosine triphosphate (ATP in at least three locations during exercise; to run the actomyosin interaction, operate sarcoplasmic reticulum calcium pumps, and operate sarcolemma sodium and potassium pumps.  Weight lifting sessions are considered to be an intermittent activity that includes only a few second bursts of high force and/or velocity movements followed by rest periods of up to several minutes. Therefore, the anaerobic pathways such as the phosphagen and glycolytic systems are the initial pathways to respond due in part to the ability to match the increased rates of ATP depletion by increasing ATP production. After the initial resting ATP stores are used up, the phosphagen system starts contributing to ATP replenishment.  This system consists of reactions from the creatine kinase (CK pathway and the adenylate kinase (AK pathway.  However, the CK pathway can only work at max capacity for a short period for resting phosphocreatine (PCr concentrations are only about 4-6 times the amount of resting ATP stores.  Once the PCr concentrations are depleted, the AK reaction will begin by using two adenosine diphosphate (ADP to form one ATP and one adenosine monophosphate (AMP. Although ATP is produced in this pathway, this production of ATP does coincide with an increased concentration of AMP. This is problematic because increased AMP levels will in turn stimulate the adenylate deaminase reaction, which will produce ammonia (NH3. This conversion of AMP into NH3 will result in the muscle cell having a net loss of total adenine nucleotides available to resynthesize ATP.  Glycolysis is the next reaction in line, which increases its role in ATP replenishment as PCr

  19. Consumption of 125I labelled fibrinogen in normal subjects

    Langer, B.; Camargo, E.E.; Reis, J.M.M. dos; Carvalho, N.; Leao, L.E.P.

    1978-01-01

    The metabolism of iodine- 125 labeled human fibrinogen is studied by using three different sets of the radiopharmaceutical (0.9, 1.3 and 1.84 iodine atoms/fibrinogen molecule ratios) in 19 normal subjects. An aliquot of 40 μCi of fibrinogem- 125 I is injected in each subject, on normal dietary conditions and blood samples are withdrawn at 30, 60, 180, 36 and 720 minutes after the injection and, thereafter, one daily sample during 10 days. The compartmental distribution of the tracer is defined by plotting plasma and serum sample counts on a semilogarithmic graph paper. A rapid phase and 3 compartments are obtained. A 'rapid' consumption half-life and a 'real' consumption half-life are defined. The fibrinogen clottability is followed up to the last blood sample by checking the ratios of serum and plasma radioactivities [pt

  20. The consumption of fibrinogen during pregnancy

    Kuijpers, J.C.

    1982-01-01

    The aim of this thesis is to investigate the consumption of fibrinogen during pregnancy, under the influence of intravascular coagulopathy. The question is, in which manner and to what degree does intravascular coagulopathy occur during the normal pregnancy and in pregnancy induced hypertension. The measurement of the biological half life of fibrinogen is performed using I 125 labelled fibrinogen. A calculation is given for the fetal radiation dose during this measurement, which is shown to be no greater than that which occurs from various natural sources of radiation. The stability of the coupling of I 125 to the fibrinogen preparation used was investigated. Nearly 93% was bound to the intact fibrinogen fraction, 5% to the non-clotting fibrinogen, 1% to the albumin and 1% appeared as free I 125 . After intravenous injection of the I 125 -fibrinogen preparation, these proportions changed a little in favour of the clottable fibrinogen fraction. (Auth.)

  1. Fibrinogen-binding and platelet-aggregation activities of a Lactobacillus salivarius septicaemia isolate are mediated by a novel fibrinogen-binding protein.

    Collins, James; van Pijkeren, Jan-Peter; Svensson, Lisbeth; Claesson, Marcus J; Sturme, Mark; Li, Yin; Cooney, Jakki C; van Sinderen, Douwe; Walker, Alan W; Parkhill, Julian; Shannon, Oonagh; O'Toole, Paul W

    2012-09-01

    The marketplace for probiotic foods is burgeoning, measured in billions of euro per annum. It is imperative, however, that all bacterial strains are fully assessed for human safety. The ability to bind fibrinogen is considered a potential pathogenicity trait that can lead to platelet aggregation, serious medical complications, and in some instances, death. Here we examined strains from species frequently used as probiotics for their ability to bind human fibrinogen. Only one strain (CCUG 47825), a Lactobacillus salivarius isolate from a case of septicaemia, was found to strongly adhere to fibrinogen. Furthermore, this strain was found to aggregate human platelets at a level comparable to the human pathogen Staphylococcus aureus. By sequencing the genome of CCUG 47825, we were able to identify candidate genes responsible for fibrinogen binding. Complementing the genetic analysis with traditional molecular microbiological techniques enabled the identification of the novel fibrinogen receptor, CCUG_2371. Although only strain CCUG 47825 bound fibrinogen under laboratory conditions, homologues of the novel fibrinogen binding gene CCUG_2371 are widespread among L. salivarius strains, maintaining their potential to bind fibrinogen if expressed. We highlight the fact that without a full genetic analysis of strains for human consumption, potential pathogenicity traits may go undetected. © 2012 Blackwell Publishing Ltd.

  2. Metabolic features of the cell danger response.

    Naviaux, Robert K

    2014-05-01

    The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental

  3. Evaluation of the Characteristics of the Adsorption of Fibrinogen ...

    ... with calcium and magnesium ions increased the amount of fibrinogen adsorbed onto it as against treatment with potassium ion (a monovalent ion). Electrostatic attraction on the surface of the treated HAP and hydrogen are responsible for the adsorption. The results are useful in fabricating bone and teeth implants that are ...

  4. Fibrinogen adsorption on blocked surface of albumin

    Holmberg, Maria; Hou, Xiaolin

    2011-01-01

    We have investigated the adsorption of albumin and fibrinogen onto PET (polyethylene terephthalate) and glass surfaces and how pre-adsorption of albumin onto these surfaces can affect the adsorption of later added fibrinogen. For materials and devices being exposed to blood, adsorption...... of fibrinogen is often a non-wanted event, since fibrinogen is part of the clotting cascade and unspecific adsorption of fibrinogen can have an influence on the activation of platelets. Albumin is often used as blocking agent for avoiding unspecific protein adsorption onto surfaces in devices designed to handle...... energies, the adsorption of both albumin and fibrinogen has been monitored simultaneously on the same sample. Information about topography and coverage of adsorbed protein layers has been obtained using AFM (Atomic Force Microscopy) analysis in liquid. Our studies show that albumin adsorbs in a multilayer...

  5. Pitfalls of radioisotope diagnosis of deep venous thromboses with /sup 125/I-fibrinogen in traumatology

    Novak, K.; Pestal, M. (Vyzkumny Ustav Traumatologicky, Brno (Czechoslovakia))

    1984-05-25

    Experience is described with the examination of deep venous thromboses of the lower extremities using /sup 125/I-fibrinogen. Intravenously administered labelled fibrinogen is taken up into the forming thrombus which may then be detected. Experience is presented with preparations of various makes. It was proved that in injured patients the biological half-life of /sup 125/I-fibrinogen is reduced to 50 hrs and less as against the standard half-life of 96.2 hrs. This is caused by fibrinogen losses owing to the injury, increased intensity of metabolic processes and the quality of the preparation being used. Injured patients should be examined using a highest quality preparation without denaturation damage to the labelled protein.

  6. Pitfalls of radioisotope diagnosis of deep venous thromboses with 125I-fibrinogen in traumatology

    Novak, K.; Pestal, M.

    1984-01-01

    Experience is described with the examination of deep venous thromboses of the lower extremities using 125 I-fibrinogen. Intravenously administered labelled fibrinogen is taken up into the forming thrombus which may then be detected. Experience is presented with preparations of various makes. It was proved that in injured patients the biological half-life of 125 I-fibrinogen is reduced to 50 hrs and less as against the standard half-life of 96.2 hrs. This is caused by fibrinogen losses owing to the injury, increased intensity of metabolic processes and the quality of the preparation being used. Injured patients should be examined using a highest quality preparation without denaturation damage to the labelled protein. (Ha)

  7. Fibrinogen adsorption on blocked surface of albumin.

    Holmberg, Maria; Hou, Xiaolin

    2011-05-01

    We have investigated the adsorption of albumin and fibrinogen onto PET (polyethylene terephthalate) and glass surfaces and how pre-adsorption of albumin onto these surfaces can affect the adsorption of later added fibrinogen. For materials and devices being exposed to blood, adsorption of fibrinogen is often a non-wanted event, since fibrinogen is part of the clotting cascade and unspecific adsorption of fibrinogen can have an influence on the activation of platelets. Albumin is often used as blocking agent for avoiding unspecific protein adsorption onto surfaces in devices designed to handle biological samples, including protein solutions. It is based on the assumption that proteins adsorbs as a monolayer on surfaces and that proteins do not adsorb on top of each other. By labelling albumin and fibrinogen with two different radioactive iodine isotopes that emit gamma radiation with different energies, the adsorption of both albumin and fibrinogen has been monitored simultaneously on the same sample. Information about topography and coverage of adsorbed protein layers has been obtained using AFM (Atomic Force Microscopy) analysis in liquid. Our studies show that albumin adsorbs in a multilayer fashion on PET and that fibrinogen adsorbs on top of albumin when albumin is pre-adsorbed on the surfaces. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

    2015-09-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  9. The Primary Role of Fibrinogen-Related Proteins in Invertebrates Is Defense, Not Coagulation

    Hanington, Patrick C.; Zhang, Si-Ming

    2010-01-01

    In vertebrates, the conversion of fibrinogen into fibrin is an essential process that underlies the establishment of the supporting protein framework required for coagulation. In invertebrates, fibrinogen-domain-containing proteins play a role in the defense response generated against pathogens; however, they do not function in coagulation, suggesting that this role has been recently acquired. Molecules containing fibrinogen motifs have been identified in numerous invertebrate organisms, and most of these molecules known to date have been linked to defense. Moreover, recent genome projects of invertebrate animals have revealed surprisingly high numbers of fibrinogen-like loci in their genomes, suggesting important and perhaps diverse functions of fibrinogen-like proteins in invertebrates. The ancestral role of molecules containing fibrinogen-related domains (FReDs) with immunity is the focus of this review, with emphasis on specific FReDs called fibrinogen-related proteins (FREPs) identified from the schistosome-transmitting mollusc Biomphalaria glabrata. Herein, we outline the range of invertebrate organisms FREPs can be found in, and detail the roles these molecules play in defense and protection against infection. PMID:21063081

  10. Metabolic and adaptive immune responses induced in mice infected ...

    This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were ...

  11. A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen

    Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J

    2011-01-01

    Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

  12. A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen

    Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J, E-mail: wang@ym.edu.tw [Institute of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Li-Nung St., Shih-Pai, Taipei, Taiwan 112 (China)

    2011-04-15

    Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

  13. Technetium-99m-human fibrinogen

    Wong, D.W.; Mishkin, F.S.

    1975-01-01

    Exogenous fibrinogen has been successfully labeled with /sup 99m/Tc using a modified electrolytic method. The exact labeling mechanism has not been determined. Experimental data suggest that the labeling process of /99m/Tc-fibrinogen is quite similar to that of /sup 99m/Tc-human serum albumin as reported earlier by Benjamin. Technetium-99m-fibrinogen is stable in human plasma or in 1 percent buffered human serum albumin. A binding efficiency of 76 percent has been achieved with approximately 25 percent clottable protein. The entire labeling procedure requires less than 1 hr of preparation time. This short labeling time in a closed system may allow development of a practical method for labeling autologous fibrinogen, thus eliminating the risk of hepatitis transmission. (U.S.)

  14. Plasma Fibrinogen in Patients With Bell Palsy.

    Zhao, Hua; Zhang, Xin; Tang, Yinda; Li, Shiting

    2016-10-01

    To determine the plasma fibrinogen level in patients with Bell palsy and explore the significances of it in Bell palsy. One hundred five consecutive patients with facial paralysis were divided into 3 groups: group I (Bell palsy), group II (temporal bone fractures), and group III (facial nerve schwannoma). In addition, 22 volunteers were defined as control group. Two milliliters fasting venous blood from elbow was collected, and was evaluated by CA-7000 Full-Automatic Coagulation Analyzer. The plasma fibrinogen concentration was significantly higher in the group of patients with Bell palsy (HB IV-VI) than that in the control group (P 0.05); similarly, there was also no marked difference between group III and control group (P >0.05). In group I, the plasma fibrinogen levels became higher with the HB grading increase. The plasma fibrinogen level of HB-VI was highest. Plasma fibrinogen has an important clinical meaning in Bell palsy, which should be used as routine examination items. Defibrinogen in treatment for patients with high plasma fibrinogen content also should be suggested.

  15. Manipulation of the metabolic response in clinical practice

    Kehlet, H

    2000-01-01

    morbidity. Effective afferent neural blockade with continuous epidural local anesthetic techniques inhibits a major part of the endocrine metabolic response, leading to improved protein economy but without important effects on inflammatory or immunologic responses. In contrast, pain treatment with other...... modalities such as nonsteroidal antiinflammatory drugs (NSAIDs) and opioids has only a small inhibitory effect on endocrine metabolic responses. Preoperative high-dose glucocorticoid therapy provides additional pain relief and improves pulmonary function, but it reduces the inflammatory response (acute......-phase proteins, cytokines, hyperthermia) and immune function. Minimally invasive surgery leaves the endocrine metabolic responses largely unaltered but reduces the inflammatory response and immune suppression. Thus several techniques are available to modify the stress responses in elective surgery patients...

  16. Metabolic response to exogenous ethanol in yeast

    In this study, we applied this approach to evaluate the effects of increasing concentration of exogenous ethanol on the Saccharomyces cerevisiae fermentative metabolism. We show that the STOCSY analysis correctly identifies the different types of correlations among the enriched metabolites involved in the fermentation, ...

  17. Plasma circulating fibrinogen stability and moderate beer consumption.

    Gorinstein, Shela; Caspi, Abraham; Zemser, Marina; Libman, Imanuel; Goshev, Ivan; Trakhtenberg, Simon

    2003-12-01

    MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences plasma lipid levels and plasma antioxidant activity in beer-consuming individuals. The connection between MBC and blood coagulation is not clearly defined. Forty-two volunteers were equally divided into experimental (EG) and control (CG) groups following coronary bypass surgery. For 30 consecutive days, only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol). A comprehensive clinical investigation of 42 patients was done. Blood samples were collected before and after the investigation for a wide range of laboratory tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC) were used to reveal possible qualitative changes. After 30 days of moderate beer consumption, positive changes in the plasma lipid levels, plasma anticoagulant and plasma antioxidant activities were registered in patients of the EG group. In 17 out of 21 patients of the same group, differences in plasma circulating fibrinogen's (PCF), secondary and tertiary structures were found. The stability of fibrinogen, expressed in thermodynamic parameters, has shown that the loosening of the structure takes place under ethanol and urea denaturation. Also fluorescence stability of PCF was decreased. No changes in the lipid levels, anticoagulant and antioxidant activity or changes in PCF were detected in patients of CG. In conclusion, for the first time after a short term of moderate beer consumption some qualitative changes in the plasma circulating fibrinogen were detected: differences in the emission peak response, fluorescence intensity and all thermodynamic data. Together, with the decrease in the PCF concentration it may lead to an elevation of the blood anticoagulant activity.

  18. Possible stimuli for strength and power adaptation : acute metabolic responses.

    Crewther, Blair; Cronin, John; Keogh, Justin

    2006-01-01

    The metabolic response to resistance exercise, in particular lactic acid or lactate, has a marked influence upon the muscular environment, which may enhance the training stimulus (e.g. motor unit activation, hormones or muscle damage) and thereby contribute to strength and power adaptation. Hypertrophy schemes have resulted in greater lactate responses (%) than neuronal and dynamic power schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors such as age, sex, training experience and nutrition may also influence the lactate responses to resistance exercise and thereafter, muscular adaptation. Although the importance of the mechanical and hormonal stimulus to strength and power adaptation is well recognised, the contribution of the metabolic stimulus is largely unknown. Relatively few studies for example, have examined metabolic change across neuronal and dynamic power schemes, and not withstanding the fact that those mechanisms underpinning muscular adaptation, in relation to the metabolic stimulus, remain highly speculative. Inconsistent findings and methodological limitations within research (e.g. programme design, sampling period, number of samples) make interpretation further difficult. We contend that strength and power research needs to investigate those metabolic mechanisms likely to contribute to weight-training adaptation. Further research is also needed to examine the metabolic responses to different loading schemes, as well as interactions across age, sex and training status, so our understanding of how to optimise strength and power development is improved.

  19. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

    Wone, B W M; Madsen, Per; Donovan, E R

    2015-01-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection...... on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols...... and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR...

  20. Metabolic responses of Haliotis diversicolor to Vibrio parahaemolyticus infection.

    Lu, Jie; Shi, Yanyan; Cai, Shuhui; Feng, Jianghua

    2017-01-01

    Vibrio parahemolyticus is a devastating bacterial pathogen that often causes outbreak of vibriosis in abalone Haliotis diversicolor. Elucidation of metabolic mechanisms of abalones in responding to V. parahemolyticus infection is essential for controlling the epidemic. In this work, 1 H NMR-based metabolomic techniques along with correlation and network analyses are used to investigate characteristic metabolites, as well as corresponding disturbed pathways in hepatopancreas and gill of H. diversicolor after V. parahemolyticus infection for 48 h. Results indicate that obvious gender- and tissue-specific metabolic responses are induced. Metabolic responses in female abalones are more clearly observed than those in males, which are primarily manifested in the accumulation of branched-chain amino acids and the depletion of organic osmolytes (homarine, betaine and taurine) in the infected gills of female abalones, as well as in the depletion of glutamate, branched-chain and aromatic amino acids in the infected hepatopancreases of female abalones. Moreover, based on major metabolic functions of the characteristic metabolites, we have found that V. parahemolyticus infection not only cause the disturbance in energy metabolism, nucleotide metabolism and osmotic balance, but also induce oxidative stress, immune stress and neurotoxic effect in different tissues with various mechanisms. Our study provides details of metabolic responses of abalones to V. parahemolyticus infection and will shed light on biochemical defence mechanisms of male and female hosts against pathogen infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Fibrinogen concentrate for bleeding - a systematic review

    Lunde, J; Stensballe, J; Wikkelsø, A

    2014-01-01

    Fibrinogen concentrate as part of treatment protocols increasingly draws attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the potential to reduce bleeding, transfusion requirement and subsequently reduce morbidity and mortality. A systematic search for randomised controlled...... trials (RCTs) and non-randomised studies investigating fibrinogen concentrate in bleeding patients was conducted up to November 2013. We included 30 studies of 3480 identified (7 RCTs and 23 non-randomised). Seven RCTs included a total of 268 patients (165 adults and 103 paediatric), and all were...... determined to be of high risk of bias and none reported a significant effect on mortality. Two RCTs found a significant reduction in bleeding and five RCTs found a significant reduction in transfusion requirements. The 23 non-randomised studies included a total of 2825 patients, but only 11 of 23 studies...

  2. Metabolic response to surgery in the cancer patient

    Brennan, M.F.

    1979-01-01

    The metabolic response to uncomplicated surgery in the patient undergoing primary therapy for malignancy is no different than the response to surgery of similar magnitude for benign disease. Hemodynamic, nutritional-endocrine, and convalescent changes are similar. However, with current aggressive approaches to the management of cancer, the patient often comes to surgery with evidence of major debilitating side effects from his progressive malignancy or from aggressive multimodality therapy. The surgeon must be aware of the consequences of the use of combination therapies on the expected metabolic response to surgery. Awareness of such problems such as the nutritional deficit will allow preventive methods to supercede mtabolic salvage procedures

  3. Two novel fibrinogen variants in the C-terminus of the B.beta.-chain: fibrinogen Rokycany and fibrinogen Znojmo

    Kotlín, R.; Reicheltová, Z.; Suttnar, J.; Salaj, P.; Hrachovinová, I.; Riedel, Tomáš; Malý, M.; Oravec, M.; Kvasnička, J.; Dyr, J. E.

    2010-01-01

    Roč. 30, č. 3 (2010), s. 311-318 ISSN 0929-5305 R&D Projects: GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z40500505 Keywords : fibrinogen * missense mutation * hypofibrinogenemia Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.539, year: 2010

  4. Composition comprising radioactive labeled-fibrinogen and albumin

    Charlton, J.C.; Gravett, D.L.

    1976-01-01

    The stability of fibrinogen is improved by mixing it with albumin, preferably at least 5 parts by weight of albumin per part by weight of fibrinogen. By this invention, iodinated ( 125 I) human fibrinogen can be stabilized with human serum albumin for use in the diagnosis of thrombi

  5. Metabolic Response to Four Weeks of Muscular Endurance Resistance Training

    John W. Farrell III

    2017-10-01

    Full Text Available Background: Previous investigations have shown that muscular endurance resistance training (MERT is conducive in improving the onset of blood lactate accumulation (OBLA. However, the metabolic response and time course for adaption is still unclear. Objective: The aims of the current study were to evaluate and track the metabolic response to an individual session of MERT as well as to assess performance adaptations of supplementing an aerobic exercise training program with four weeks of MERT. Methods: Seventeen aerobically active men were randomly assigned to either the experimental (EX or control group (CON, 9 EX and 8 CON. Baseline measures included a graded exercise test (GXT and 1-repetition maximum (1RM testing for leg press (LP, leg curl (LC, and leg extension (LE. CON continued their regular aerobic activity while the EX supplemented their regular aerobic exercise with 4 weeks of MERT. Results: No significant group differences were observed for all pre-training variables. Following four weeks of training no significant differences in cardiorespiratory or metabolic variables were observed for either group. However, significant improvements in LC and LE 1-RM were observed in EX compared to CON. Substantial accumulations in blood lactate were observed following each MERT session. Conclusion: Four weeks of MERT did not improve cardiorespiratory or metabolic variables, but did significantly improve LC and LE. MERT was also observed to induce a blood lactate response similar to that of HIIT. These findings suggest greater than four weeks is need to see metabolic adaptations conducive for improved aerobic performance using MERT.

  6. Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

    Yuanyuan Zhang

    2014-06-01

    Full Text Available Erythropoietin (EPO regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR, suggest the potential for EPO response in metabolism and disease.

  7. Structural and metabolic responses of Ceratophyllum demersum to ...

    Eutrophication in water bodies affects the growth of aquatic plants. In this study, we conducted static experiments to better understand the structural and metabolic responses of Ceratophyllum demersum under eutrophication conditions. The anatomical structure, nitrogen (N) and phosphorous (P) levels in tissue, ...

  8. Modeling metabolic response to changes of enzyme amount in ...

    Based on the work of Hynne et al. (2001), in an in silico model of glycolysis, Saccharomyces cerevisiae is established by introducing an enzyme amount multiple factor (.) into the kinetic equations. The model is aimed to predict the metabolic response to the change of enzyme amount. With the help of .α, the amounts of ...

  9. Long-term salt stress responsive growth, carbohydrate metabolism ...

    We investigated the long-term responses of tobacco tissues to salt stress, with a particular interest for growth parameters, proline (Pro) accumulation, and carbohydrate metabolism. Exposure of 17-day-old tobacco plants to 0.2 M NaCl was followed by a higher decrease in dry matter in roots than shoots with a decrease of ...

  10. Metabolic changes in serum metabolome in response to a meal.

    Shrestha, Aahana; Müllner, Elisabeth; Poutanen, Kaisa; Mykkänen, Hannu; Moazzami, Ali A

    2017-03-01

    The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal. Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography-mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control. The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body's energy source from β-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses. The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

  11. Platelet fibrinogen binding in Basset Hound Hereditary Thrombopathy

    Patterson, W.; Estry, D.; Schwartz, K.; Bell, T.

    1986-01-01

    Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10 -5 M ADP in the presence of 125 I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- 3971 molecules of fibrinogen per platelet. The BHT platelet aggregation defect does not seem to be caused by a functionally abnormal GP IIb-IIIa complex, since BHT platelets bind normal amounts of fibrinogen. The results suggest that fibrinogen binding is not sufficient for platelet aggregation, and other factors, perhaps receptor mobility and membrane phospholipid content should be investigated in BHT

  12. LKB1 promotes metabolic flexibility in response to energy stress.

    Parker, Seth J; Svensson, Robert U; Divakaruni, Ajit S; Lefebvre, Austin E; Murphy, Anne N; Shaw, Reuben J; Metallo, Christian M

    2017-09-01

    The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using 13 C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1. Re-expression of LKB1 also increased the capacity of cells to oxidize major mitochondrial substrates, including pyruvate, fatty acids, and glutamine. Furthermore, LKB1 expression promoted an adaptive response to energy stress induced by anchorage-independent growth. Finally, this diminished adaptability sensitized LKB1-deficient cells to combinatorial inhibition of mitochondrial complex I and glutaminase. Together, our data implicate LKB1 as a major regulator of adaptive metabolic reprogramming and suggest synergistic pharmacological strategies for mitigating LKB1-deficient NSCLC tumor growth. Copyright © 2016. Published by Elsevier Inc.

  13. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    Chen YS

    2014-01-01

    Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

  14. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

    Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

    2015-04-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

  15. Metabolic Response of Maize Roots to Hyperosmotic Shock 1

    Spickett, Corinne M.; Smirnoff, Nicholas; Ratcliffe, R. George

    1992-01-01

    31P nuclear magnetic resonance spectroscopy was used to study the response of maize (Zea mays L.) root tips to hyperosmotic shock. The aim was to identify changes in metabolism that might be relevant to the perception of low soil water potential and the subsequent adaptation of the tissue to these conditions. Osmotic shock was found to result in two different types of response: changes in metabolite levels and changes in intracellular pH. The most notable metabolic changes, which were produced by all the osmotica tested, were increases in phosphocholine and vacuolar phosphate, with a transient increase in cytoplasmic phosphate. It was observed that treatment with ionic and nonionic osmotica produced different effects on the concentrations of bioenergetically important metabolites. It is postulated that these changes are the result of hydrolysis of phosphatidylcholine and other membrane phospholipids, due to differential activation of specific membrane-associated phospholipases by changes in the surface tension of the plasmalemma. These events may be important in the detection of osmotic shock and subsequent acclimatization. A cytoplasmic alkalinization was also observed during hyperosmotic treatment, and this response, which is consistent with the activation of the plasmalemma H+-ATPase, together with the other metabolic changes, may suggest the existence of a complex and integrated mechanism of osmoregulation. PMID:16669012

  16. AMPK regulates metabolism and survival in response to ionizing radiation

    Zannella, Vanessa E.; Cojocari, Dan; Hilgendorf, Susan; Vellanki, Ravi N.; Chung, Stephen; Wouters, Bradly G.; Koritzinsky, Marianne

    2011-01-01

    Background and purpose: AMPK is a metabolic sensor and an upstream inhibitor of mTOR activity. AMPK is phosphorylated by ionizing radiation (IR) in an ATM dependent manner, but the cellular consequences of this phosphorylation event have remained unclear. The objective of this study was to assess whether AMPK plays a functional role in regulating cellular responses to IR. Methods: The importance of AMPK expression for radiation responses was investigated using both MEFs (mouse embryo fibroblasts) double knockout for AMPK α1/α2 subunits and human colorectal carcinoma cells (HCT 116) with AMPK α1/α2 shRNA mediated knockdown. Results: We demonstrate here that IR results in phosphorylation of both AMPK and its substrate, ACC. IR moderately stimulated mTOR activity, and this was substantially exacerbated in the absence of AMPK. AMPK was required for IR induced expression of the mTOR inhibitor REDD1, indicating that AMPK restrains mTOR activity through multiple mechanisms. Likewise, cellular metabolism was deregulated following irradiation in the absence of AMPK, as evidenced by a substantial increase in oxygen consumption rates and lactate production. AMPK deficient cells showed impairment of the G1/S cell cycle checkpoint, and were unable to support long-term proliferation during starvation following radiation. Lastly, we show that AMPK proficiency is important for clonogenic survival after radiation during starvation. Conclusions: These data reveal novel functional roles for AMPK in regulating mTOR signaling, cell cycle, survival and metabolic responses to IR.

  17. Do diabetes and obesity affect the metabolic response to exercise?

    Plomgaard, Peter; Weigert, Cora

    2017-07-01

    Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

  18. Biochemical and biological properties of the binding of human fibrinogen to M protein in group A streptococci

    Whitnack, E.; Beachey, E.H.

    1985-01-01

    Fibrinogen is known to bind to group A streptococci and precipitate with extracts containing streptococcal M protein. The authors have previously shown that the binding of fibrinogen to M-positive streptococci prevents opsonization by complement and protects that organism from phagocytosis in nonimmune blood. In the present study, they used 3 H-labeled fibrinogen, a highly purified peptide fragment of type 24 M protein (pep M24), and anti-pep M sera to show that fibrinogen binds to M-positive streptococci with high affinity; occupation of the high-affinity binding sites suffices to protect the organism from phagocytosis; proteolytic treatments that remove M protein from streptococcal cells abolish binding; binding is competitively inhibited by anti-pep M sera; pep M24 precipitates fibrinogen; and binding to type 24 cells is inhibited by pep M24. They conclude that M protein is the cell surface structure principally responsible for binding fibrinogen on the surface of M-positive streptococci and that this binding contributes to the known antiopsonic property of M proteins

  19. Relationship between physical activity and plasma fibrinogen concentrations in adults without chronic diseases.

    Manuel A Gomez-Marcos

    Full Text Available To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR, and plasma fibrinogen concentrations.A cross-sectional study in a previously established cohort of healthy subjects was performed. This study analyzed 1284 subjects who were included in the EVIDENT study (mean age 55.0±13.6 years; 60.90% women. Fibrinogen concentrations were measured in blood plasma. Physical activity was assessed with a 7-day PAR (metabolic equivalents (METs/hour/week and GT3X ActiGraph accelerometer (counts/minute for 7 days.Physical exercise, which was evaluated with both an accelerometer (Median: 237.28 counts/minute and 7-day PAR (Median: 8 METs/hour/week. Physical activity was negatively correlated with plasma fibrinogen concentrations, which was evaluated by counts/min (r = -0.100; p<0.001 and METs/hour/week (r = -0.162; p<0.001. In a multiple linear regression analysis, fibrinogen concentrations of the subjects who performed more physical activity (third tertile of count/minute and METs/hour/week respect to subjects who performed less (first tertile, maintained statistical significance after adjustments for age and others confounders (β = -0.03; p = 0.046 and β = -0.06; p<0.001, respectively.Physical activity, as assessed by accelerometer and 7-day PAR, was negatively associated with plasma fibrinogen concentrations. This relation is maintained in subjects who performed more exercise even after adjusting for age and other confounders.

  20. Fibrinogen Reduction During Selective Plasma Exchange due to Membrane Fouling.

    Ohkubo, Atsushi; Okado, Tomokazu; Miyamoto, Satoko; Hashimoto, Yurie; Komori, Shigeto; Yamamoto, Motoki; Maeda, Takuma; Itagaki, Ayako; Yamamoto, Hiroko; Seshima, Hiroshi; Kurashima, Naoki; Iimori, Soichiro; Naito, Shotaro; Sohara, Eisei; Uchida, Shinichi; Rai, Tatemitsu

    2017-06-01

    Fibrinogen is substantially reduced by most plasmapheresis modalities but retained in selective plasma exchange using Evacure EC-4A10 (EC-4A). Although EC-4A's fibrinogen sieving coefficient is 0, a session of selective plasma exchange reduced fibrinogen by approximately 19%. Here, we investigated sieving coefficient in five patients. When the mean processed plasma volume was 1.15 × plasma volume, the mean reduction of fibrinogen during selective plasma exchange was approximately 15%. Fibrinogen sieving coefficient was 0 when the processed plasma volume was 1.0 L, increasing to 0.07 when the processed plasma volume was 3.0 L, with a mean of 0.03 during selective plasma exchange. When fibrinogen sieving coefficient was 0, selective plasma exchange reduced fibrinogen by approximately 10%. Scanning electron microscopy images revealed internal fouling of EC-4A's hollow fiber membrane by substances such as fibrinogen fibrils. Thus, fibrinogen reduction by selective plasma exchange may be predominantly caused by membrane fouling rather than filtration. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  1. Deciphering hepatocellular responses to metabolic and oncogenic stress

    Kathrina L. Marcelo

    2015-08-01

    Full Text Available Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (MΦ, and sinusoidal endothelial cells (SEC play functionally important and interdependent roles in adaptive processes such as obesity and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. We developed a strategy for the simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression. To demonstrate the utility and applicability of this technique, we quantified liver cell-specific responses to high-fat diet (HFD or diethylnitrosamine (DEN, a liver-specific carcinogen, and found that while there was only a marginal increase in hepatocyte number, MΦ and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, MΦ and SEC identified characteristic gene signatures that define each cell type in their distinct physiological or pathological states. Integration of hepatic gene signatures with available human obesity and liver cancer microarray data provides further insight into the cell-specific responses to metabolic or oncogenic stress. Our data reveal unique gene expression patterns that serve as molecular “fingerprints” for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to metabolic and oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the continuum from metabolic disruption to obesity and ultimately hepatic cancer.

  2. Two cases of congenital dysfibrinogenemia associated with thrombosis - Fibrinogen Praha III and Fibrinogen Plzen

    Kotlín, R.; Reicheltová, Z.; Malý, M.; Suttnar, J.; Sobotková, A.; Salaj, P.; Hirmerová, J.; Riedel, Tomáš; Dyr, J. E.

    2009-01-01

    Roč. 102, č. 3 (2009), s. 479-486 ISSN 0340-6245 R&D Projects: GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z40500505 Keywords : dysfibrinogenemia * fibrinogen * missense mutation Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.451, year: 2009

  3. Thermal sensation and thermophysiological responses with metabolic step-changes

    Goto, Tomonobu; Toftum, Jørn; deDear, Richard

    2006-01-01

    at sedentary activity. In a second experimental series, subjects alternated between rest and exercise as well as between exercise at different intensities at two temperature levels. Measurements comprised skin and oesophageal temperatures, heart rate and subjective responses. Thermal sensation started to rise....... The sensitivity of thermal sensation to changes in core temperature was higher for activity down-steps than for up-steps. A model was proposed that estimates transient thermal sensation after metabolic step-changes. Based on predictions by the model, weighting factors were suggested to estimate a representative...... average metabolic rate with varying activity levels, e.g. for the prediction of thermal sensation by steady-state comfort models. The activity during the most recent 5 min should be weighted 65%, during the prior 10-5 min 25% and during the prior 20-10 min 10%....

  4. Effect of radiographic contrast agents on leukocyte metabolic response

    Hernanz-Schulman, M. [Dept. of Pediatric Radiology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Vanholder, R.; Waterloos, M.A. [Dept. of Internal Medicine, Nephrology Section, University Hospital, Gent (Belgium); Hakim, R.; Schulman, G. [Department of Nephrology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2000-06-01

    Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significat activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these dsata serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

  5. Effect of radiographic contrast agents on leukocyte metabolic response

    Hernanz-Schulman, M.; Vanholder, R.; Waterloos, M.A.; Hakim, R.; Schulman, G.

    2000-01-01

    Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significant activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these data serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

  6. Skeletal changes in congenital fibrinogen abnormalities

    Lagier, R.; Bouvier, C.A.; van Strijthem, N.

    1980-01-01

    We report anatomico-radiologic study of humerus, femur, and tibia from a case of total congenital afibrinogenemia. Juxtatrabecular hemorrhages occur mainly in metaphyses and seem to be related to normal lines of stress. They may lead to the formation of intraosseous cysts and to a remodelling of bone trabeculae. The radiologic lesions in a second case, diagnosed as congenital dysfibrinogenemia, are similar to those found in Case 1 (femoral trabeculae remodelling) but also resemble some alterations described in hemophilia (pseudotumor of the right iliac bone). Anatomic study of the lesions in Case 2 was not possible. The significance of these observations could be better defined by a more extended skeletal study (radiologic and when feasible anatomic) of patients with congenital clotting defects and especially with inherited disorders of the fibrinogen molecule. It would also be worthwhile investigating manifest or latent hemostatic disorders (particularly at the fibrinogen level) in patients with solitary or aneurysmal bone cysts, and even with bone infarct or unexplained trabecular remodelling.

  7. Effect of vitamins C and E alone and in combination with each other on LDL and fibrinogen in streptozotocin induced diabetic rats

    Talat, A.; Khan, T.B.; Mahmood, S.

    2011-01-01

    Diabetes mellitus is a heterogeneous group of disorders, manifested by raised plasma glucose concentration and disturbances of glucose metabolism Diabetes mellitus is a complex of metabolic disorders affecting different systems of body. The main etiology of mortality and high percentage of morbidity in patients with diabetes mellitus is atherosclerosis. The vascular endothelium overlying lesion - prone arterial sites shows increased permeability to plasma proteins, LDL and fibrinogen. High plasma fibrinogen concentration in adults is associated with elevated risk of coronary heart disease and stroke. Treatment with antioxidants like vitamin C and vitamin E reduces diabetic complications. The aim of this study was to determine the effect of antioxidants vitamin C and E in lowering the fibrinogen and LDL levels. Present study was conducted on 48 albino rats. They were divided into four groups. Dia-betes was induced in all rats by giving streptozotocin 65 mg/kg intraperitoneally. First group was control diabetic. Second group was given vitamin C in a dose of 150 mg/kg b.w/day and third group was given vita-min E in a dose of 100 mg/kg b.w/day. Fourth group was given vitamin C with vitamin E intraperitoneally in the same doses. Effects of vitamin C and E were observed on serum LDL and plasma fibrinogen level by using commercially available kits. LDL cholesterol was decreased in groups B, C and D as compared to group A. Fibrinogen level was decreased in - group B and D and increased in group C. Vitamin C alone and in combination with vitamin E help in ameliorating atherosclerosis by decreasing LDL and fibrinogen levels. Vitamin E lowers LDL level but not fibrinogen level. There is a synergistic action of vitamin E and C in lowering fibrinogen and LDL level. (author)

  8. Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

    Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

    2017-11-01

    Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered ( P citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

  9. Quality asurance of iodinated (125 I) human fibrinogen

    Vines, E.J.

    1980-05-01

    The radiopharmaceutical iodinated ( 125 I) human fibrinogen is currently used for the detection of deep vein thrombosis in the legs, a fairly common post-surgical complication. A comprehensive quality assurance programme for ( 125 I) - human fibrinogen has been determined for routine use at the Australian Radiation Laboratory, with adaptions necessary for hospital quality control testing

  10. Two novel mutations in the fibrinogen .gamma. nodule

    Kotlín, R.; Pastva, O.; Štikarová, J.; Hlaváčková, A.; Suttnar, J.; Chrastinová, L.; Riedel, Tomáš; Salaj, P.; Dyr, J. E.

    2014-01-01

    Roč. 134, č. 4 (2014), s. 901-908 ISSN 0049-3848 R&D Projects: GA ČR GBP205/12/G118 Institutional support: RVO:61389013 Keywords : abnormal fibrinogens * hereditary coagulation disorders * fibrinogen Subject RIV: BO - Biophysics Impact factor: 2.447, year: 2014

  11. The metabolic responses to aerial diffusion of essential oils.

    Yani Wu

    Full Text Available Anxiety disorders are the most prevalent psychiatric disorders and affect a great number of people worldwide. Essential oils, take effects through inhalation or topical application, are believed to enhance physical, emotional, and spiritual well-being. Although clinical studies suggest that the use of essential oils may have therapeutic potential, evidence for the efficacy of essential oils in treating medical conditions remains poor, with a particular lack of studies employing rigorous analytical methods that capture its identifiable impact on human biology. Here, we report a comprehensive gas chromatography time-of-flight mass spectrometry (GC-TOFMS based metabonomics study that reveals the aromas-induced metabolic changes and the anxiolytic effect of aromas in elevated plus maze (EPM induced anxiety model rats. The significant alteration of metabolites in the EPM group was attenuated by aromas treatment, concurrent with the behavioral improvement with significantly increased open arms time and open arms entries. Brain tissue and urinary metabonomic analysis identified a number of altered metabolites in response to aromas intervention. These metabolic changes included the increased carbohydrates and lowered levels of neurotransmitters (tryptophan, serine, glycine, aspartate, tyrosine, cysteine, phenylalanine, hypotaurine, histidine, and asparagine, amino acids, and fatty acids in the brain. Elevated aspartate, carbohydrates (sucrose, maltose, fructose, and glucose, nucleosides and organic acids such as lactate and pyruvate were also observed in the urine. The EPM induced metabolic differences observed in urine or brain tissue was significantly reduced after 10 days of aroma inhalation, as noted with the loss of statistical significance on many of the metabolites in the aroma-EPM group. This study demonstrates, for the first time, that the metabonomics approach can capture the subtle metabolic changes resulting from exposure to essential oils

  12. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage

    Wikkelsø, A J; Edwards, H M; Afshari, A

    2015-01-01

    BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients...... and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin ... concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence...

  13. Exploration by radioactive fibrinogen of intrarenal coagulation phenomena. Preliminary results

    Simon, Jacques.

    1974-01-01

    The participation of fibrin deposits in kidney pathology was studied by the use of a radioactive tracer involved in the coagulation phenomenon: iodine 131-labelled fibrinogen. The isotopic exploration consists of a fibrinogen kinetics study combined with external counting over the kidney regions. The different stages of the procedure are described: separation, purification and labelling of fibrinogen; characteristics of the radioactive fibrinogen used; practical details of the examination itself; data analysis method. A chapter devoted to verifications and discussions of the procedure is followed by a report on the exploration of intrarenal coagulation phenomena in 30 kidney disease patients. In conclusion, the study of fibrinogen kinetics is considered as the most suitable method to detect local or slight intravascular coagulation phenomena. The sensitivity of the isotopic exploration is very satisfactory. The main criticism directed against this method is that the exploration is general and therefore blind [fr

  14. Liposoluble vitamins in Crustacean feed: Metabolic and Histological responses.

    Fernández-Gimenez, Analía Verónica

    2016-05-01

    Vitamins are vital for normal growth and survival of living organisms and they are distributed in feedstuffs in small quantities. This review is focused on the liposoluble vitamins (A, D, E and K) in the diets and metabolic responses of the Argentine penaeoid shrimps Pleoticus muelleri and Artemesia longinaris, distributed along the South American coast line. Growth, survival and histological analyses serve as indicators of the nutritional value derived from vitamin deficiency. Liposoluble vitamins are also related to stress, antioxidant defense and immune response of shrimps. Effective diet for shrimp culture that provide not only macronutrients including protein and lipid but also micronutrients such as vitamins for optimal growth is an ever improving subject. This review may help formulating suitable feeds for shrimps.

  15. Do diabetes and obesity affect the metabolic response to exercise?

    Plomgaard, Peter; Weigert, Cora

    2017-01-01

    control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation...... of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent......PURPOSE OF REVIEW: Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. RECENT FINDINGS: Poor glycemic...

  16. Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

    Hilsted, J; Richter, E; Madsbad, S

    1987-01-01

    with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients......Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients....... To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients...

  17. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

    Lidia De Riccardis

    2016-12-01

    Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  18. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.

    De Riccardis, Lidia; Ferramosca, Alessandra; Danieli, Antonio; Trianni, Giorgio; Zara, Vincenzo; De Robertis, Francesca; Maffia, Michele

    2016-12-01

    Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  19. Turnover of radio-iodinated and biosynthetically labelled fibrinogen in rhesus monkeys

    Moza, A.K.

    1982-01-01

    Successful radio-iodination of monkey fibrinogen using a previously documented method for rabbit fibrinogen is reported. The label was securely bound to fibrinogen without any evidence of polymerisation. Turnover rates and other kinetic parameters of fibrinogen using 125 I-fibrinogen have been compared with those obtained with biosynthetically labelled donor 75 Se-fibrinogen. Both studies yielded identical results. The values for normal monkeys showed a half life of 43.8 +- 1.03 h with 125 I-fibrinogen and 47.15 +- 1.24 with 75 Se-fibrinogen. The turnover rate of endogenous 75 Se-fibrinogen following administration of 75 Se-selenomethionine has also been studied. The half disappearance time value of 100.34 h was much longer than the t1/2 values obtained with either 125 I or 75 Se-fibrinogen. This is believed to be due the staggered input of fibrinogen molecules from the liver. (author)

  20. Identification and characterization of the fibrinogen-like domain of fibrinogen-related proteins in the mosquito, Anopheles gambiae, and the fruitfly, Drosophila melanogaster, genomes

    Zhao Qin

    2005-09-01

    Full Text Available Abstract Background The fibrinogen-like (FBG domain, which consists of approximately 200 amino acid residues, has high sequence similarity to the C-terminal halves of fibrinogen β and γ chains. Fibrinogen-related proteins (FREPs, which contain FBG domains in their C-terminal region, are found universally in vertebrates and invertebrates. In invertebrates, FREPs are involved in immune responses and other aspects of physiology. To understand the complexity of this family in insects, we analyzed FREPs in the mosquito genome and made comparisons to FREPs in the fruitfly genome. Results By using the genome data of the mosquito, Anopheles gambiae, 53 FREPs were identified, whereas only 20 members were found in the Drosophila melanogaster genome. Using sequence profile analysis, we found that FBG domains have high sequence similarity and are highly conserved throughout the FBG domain region. By secondary structure analysis and comparison, the FBG domains of FREPs are predicted to function in recognition of carbohydrates and their derivatives on the surface of microorganisms in innate immunity. Conclusion Detailed sequence and structural analysis discloses that the FREP family contains FBG domains that have high sequence similarity in the A. gambiae genome. Expansion of the FREP family in mosquitoes during evolutionary history is mainly accounted for by a major expansion of the FBG domain architecture. The characterization of the FBG domains in the FREP family is likely to aid in the experimental analysis of the ability of mosquitoes to recognize parasites in innate immunity and physiologies associated with blood feeding.

  1. Discriminating response groups in metabolic and regulatory pathway networks.

    Van Hemert, John L; Dickerson, Julie A

    2012-04-01

    Analysis of omics experiments generates lists of entities (genes, metabolites, etc.) selected based on specific behavior, such as changes in response to stress or other signals. Functional interpretation of these lists often uses category enrichment tests using functional annotations like Gene Ontology terms and pathway membership. This approach does not consider the connected structure of biochemical pathways or the causal directionality of events. The Omics Response Group (ORG) method, described in this work, interprets omics lists in the context of metabolic pathway and regulatory networks using a statistical model for flow within the networks. Statistical results for all response groups are visualized in a novel Pathway Flow plot. The statistical tests are based on the Erlang distribution model under the assumption of independent and identically Exponential-distributed random walk flows through pathways. As a proof of concept, we applied our method to an Escherichia coli transcriptomics dataset where we confirmed common knowledge of the E.coli transcriptional response to Lipid A deprivation. The main response is related to osmotic stress, and we were also able to detect novel responses that are supported by the literature. We also applied our method to an Arabidopsis thaliana expression dataset from an abscisic acid study. In both cases, conventional pathway enrichment tests detected nothing, while our approach discovered biological processes beyond the original studies. We created a prototype for an interactive ORG web tool at http://ecoserver.vrac.iastate.edu/pathwayflow (source code is available from https://subversion.vrac.iastate.edu/Subversion/jlv/public/jlv/pathwayflow). The prototype is described along with additional figures and tables in Supplementary Material. julied@iastate.edu Supplementary data are available at Bioinformatics online.

  2. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

    Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

    2008-01-01

    Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

  3. Effect of Metformin on Plasma Fibrinogen Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

    Simental-Mendia, Luis E; Pirro, Matteo; Atkin, Stephen L; Banach, Maciej; Mikhailidis, Dimitri P; Sahebkar, Amirhossein

    2018-01-01

    Fibrinogen is a key mediator of thrombosis and it has been implicated in the pathogenesis of atherosclerosis. Because metformin has shown a potential protective effect on different atherothrombotic risk factors, we assessed in this meta-analysis its effect on plasma fibrinogen concentrations. A systematic review and meta-analysis was carried out to identify randomized placebo-controlled trials evaluating the effect of metformin administration on fibrinogen levels. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases (by June 2, 2017) and quality of studies was performed according to Cochrane criteria. Quantitative data synthesis was conducted using a random-effects model and sensitivity analysis by the leave-one-out method. Meta-regression analysis was performed to assess the modifiers of treatment response. Meta-analysis of data from 9 randomized placebo-controlled clinical trials with 2302 patients comprising 10 treatment arms did not suggest a significant change in plasma fibrinogen concentrations following metformin therapy (WMD: -0.25 g/L, 95% CI: -0.53, 0.04, p = 0.092). The effect size was robust in the leave-one-out sensitivity analysis and remained non-significant after omission of each single study from the meta-analysis. No significant effect of metformin on plasma fibrinogen concentrations was demonstrated in the current meta-analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Antibody functionalized graphene biosensor for label-free electrochemical immunosensing of fibrinogen, an indicator of trauma induced coagulopathy.

    Saleem, Waqas; Salinas, Carlos; Watkins, Brian; Garvey, Gavin; Sharma, Anjal C; Ghosh, Ritwik

    2016-12-15

    An antibody, specific to fibrinogen, has been covalently attached to graphene and deposited onto screen printed electrodes using a chitosan hydrogel binder to prepare an inexpensive electrochemical fibrinogen biosensor. Fourier Transform Infrared (FT-IR) spectroscopy has been utilized to confirm the presence of the antibody on the graphene scaffold. Electrochemical Impedance Spectroscopy (EIS) has been utilized to demonstrate that the biosensor responds in a selective manner to fibrinogen in aqueous media even in the presence of plasminogen, a potentially interfering molecule in the coagulopathy cascade. Furthermore, the biosensor was shown to reliably sense fibrinogen in the presence of high background serum albumin levels. Finally, we demonstrated detection of clinically relevant fibrinogen concentrations (938-44,542μg/dL) from human serum and human whole blood samples using this biosensor. This biosensor can potentially be used in a point-of-care device to detect the onset of coagulopathy and monitor response following therapeutic intervention in trauma patients. Thus this biosensor may improve the clinical management of patients with trauma-induced coagulopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Cell Wall Metabolism in Response to Abiotic Stress

    Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine

    2015-01-01

    This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

  6. 111In-platelet and 125I-fibrinogen deposition in the lungs in experimental acute pancreatitis

    Goulbourne, I.A.; Watson, H.; Davies, G.C.

    1987-01-01

    An experimental model of acute pancreatitis in rats has been used to study intrapulmonary 125 I-fibrinogen and 111 In-platelet deposition. Pancreatitis caused a significant increase in wet lung weight compared to normal, and this could be abolished by heparin or aspirin pretreatment. 125 I-fibrinogen was deposited in the lungs of animals to a significantly greater degree than in controls (P less than 0.01). 125 I-fibrinogen deposition was reduced to control levels by pretreatment with aspirin or heparin (P less than 0.05). The uptake of radiolabeled platelets was greater in pancreatitis than in controls (P less than 0.001). Pancreatitis appears to be responsible for platelet entrapment in the lungs. Platelet uptake was reduced by heparin treatment but unaffected by aspirin therapy

  7. Metabolic and Transcriptional Response to Cofactor Perturbations in Escherichia coli

    Holm, Anders Koefoed; Blank, L.M.; Oldiges, M.

    2010-01-01

    Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli...... of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli....

  8. Tritiated bovine fibrinogen labelled in fibrinopeptide A region

    Wegrzynowicz, Z.; Kloczewiak, M.; Kopec, M.

    1974-01-01

    The method is described for labelling of bovine fibrinogen with 3 H-AcOAc. Preparations labelled at pH 7.8 with 10 to 40 molar excess of 3 H-AcOAc were found to contain 8 to 13 moles of acetyl residues per mole of fibrinogen. The content of clottable protein and UV spectra were unchanged as compared with control unlabelled preprations. The rate of clotting with thrombin was only slightly affected. The investigations on distribution of 3 H in products of proteolysis of 3 H-fibrinogen by thrombin and plasmin demonstrated a preferential labelling of fibrinopeptide A, absence of radioactive tracer in fibrinopeptide B, significantly higher specific radioactivity of fragment E than that of fragment D. Incorporation of the label into fibrinopeptide A opens the possibility for application of 3 H-fibrinogen as a convenient substrate for selective investigations on the enzymatic phase of clotting. (author)

  9. Uptake, accumulation and metabolic response of ferricyanide in weeping willows.

    Yu, Xiao-Zhang; Gu, Ji-Dong

    2009-01-01

    The remediation potential and metabolic responses of plants to ferricyanide were investigated using pre-rooted weeping willows (Salix babylonica L.) grown hydroponically in growth chambers and treated with potassium ferricyanide. Positive responses were observed for the plants exposed to cyanide recovered in plant biomass was constant in all treatments, indicating that transport is a major limiting step for the uptake of ferricyanide by plants. The majority of the ferricyanide taken up from the growth media was possibly assimilated during transport through plants. The velocity of the removal processes can be described by Michaelis-Menten kinetics, and the half-saturation constant (K(M)) and the maximum removal capacity (v(max)) were estimated to be 228.1 mg CN L(-1) and 36.43 mg CN kg(-1) d(-1), respectively, using non-linear regression methods. These results suggest that weeping willows can take up, transport and assimilate ferricyanide; and phytoremediation is an option for cleaning up the environmental sites contaminated with cyanide complexes.

  10. Fibrinogen concentrates for bleeding trauma patients: what is the evidence?

    Meyer, Martin; Ostrowski, S R; Windeløv, N A

    2011-01-01

    A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions.......A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions....

  11. Fibrinogen and alpha(1)-antitrypsin in COPD exacerbations

    Sylvan Ingebrigtsen, Truls; Marott, J. L.; Rode, L.

    2015-01-01

    Background We tested the hypotheses that fibrinogen and alpha(1)-antitrypsin are observationally and genetically associated with exacerbations in COPD. Methods We studied 13 591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455...... and exacerbations in instrumental variable analyses. Results Elevated fibrinogen and alpha(1)-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p...

  12. Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis.

    Wood, C M; Milligan, C L; Walsh, P J

    1999-08-01

    Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.

  13. Granulocyte-platelet interactions and platelet fibrinogen receptor exposure

    Kornecki, E.; Ehrlich, Y.H.; Egbring, R.; Gramse, M.; Seitz, R.; Eckardt, A.; Lukasiewicz, H.; Niewiarowski, S.

    1988-01-01

    The authors have examined the interaction of human granulocyte elastase with human platelets. Incubation of human platelets with human granulocyte elastase exposed active fibrinogen-binding sites as evidenced by 125 I-labeled fibrinogen binding and spontaneous fibrinogen-induced platelet aggregation. The aggregation of platelets by fibrinogen occurred at low concentrations of human granulocyte elastase. Platelets pretreated with human granulocyte elastase exposed an average of 10,500 fibrinogen-binding sites per platelet, i.e., about one-third the number of binding sites exposed by optimal concentrations of ADP. With the use of a polyclonal antiplatelet membrane antibody, the glycoproteins IIb (GPIIb), IIIa (GPIIIa), and a 60,000-Da (60 kDa) protein (66 kDa in a reduced system) derived from GPIIIa were immunoprecipitated from the surface of detergent extracts of human 125 I-radiolabeled platelets pretreated with increasing concentrations of human granulocyte elastase. They conclude that (1) the proteolytic action of human granulocyte elastase on platelet GPIIIa results in the formation of two major hydrolytic products, and (2) human granulocyte elastase exposes active fibrongen-binding sites associated with the GPIIb/GPIIIa complex, resulting in direct platelet aggregation by fibrinogen

  14. [Perioperative fibrinogen concentrations in cardiac surgery with cardiopulmonary bypass].

    Uji, Makiko; Terada, Yuki; Noguchi, Teruo; Nishida, Takaya; Hasuwa, Kyoko; Shinohara, Kozue; Kumano, Hotaka; Ishimura, Naoko; Nishiwada, Makoto

    2012-08-01

    Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) need many blood products due to deficiency of coagulation factors. Blood transfusion therapy in patients with excessive bleeding after CPB is generally empiric. We checked and studied the fibrinogen concentration and transfusion, as well as bleeding amount in the perioperative period. The study was approved by our institutional ethics committee. Thirty patients were studied. Blood samples were obtained at the induction of anesthesia (before CPB), at the end of CPB, at the end of operation, and on the next morning, or before the patient was given fresh frozen plasma in the intensive care unit. For all cases, fibrinogen concentration and platelet concentration were lowest at the end of CPB. Fibrinogen concentration rose up to before CPB level on the next morning. The group in which fibrinogen concentration was less than 150 mg x dl(-1) at the end of CPB consumed more blood products than the group with fibrinogen concentration of over 150 mg x dl(-1). Blood transfusion therapy based on fibrinogen concentration is needed to maintain adequacy of the perioperative blood transfusion and blood conservation in cardiac surgery.

  15. Acute metabolic and physiologic response of goats to narcosis

    Schatte, C. L.; Bennett, P. B.

    1973-01-01

    Assessment of the metabolic consequences of exposure to elevated partial pressures of nitrogen and helium under normobaric and hyperbaric conditions in goats. The results include the finding that hyperbaric nitrogen causes and increase in metabolic rate and a general decrease in blood constituent levels which is interpreted as reflecting a shift toward fatty acid metabolism at the expense of carbohydrates. A similar but more pronounced pattern was observed with hyperbaric helium.

  16. Prothrombin Time, Activated Partial Thromboplastin Time, Fibrinogen, dan D-dimer Sebagai Prediktor Decompensated Disseminated Intravascular Coagulation Sisseminated pada Sepsis

    Fenny

    2011-03-01

    Full Text Available Sepsis is a systemic response to infection especially in pneumonia case. Sepsis can cause complications such as disseminated intravascular coagulation (DIC which can be divided into compensated and decompensated DIC. The purpose of this study was to assess whether the value of prothrombin time (PT, activated partial thromboplastin time (aPTT, fibrinogen, and D-dimer levels can be used as predictors of decompensated DIC in sepsis patients. This study was conducted at the Laboratory of Clinical Pathology Rumah Sakit Hasan Sadikin Bandung since September 2008 to June 2010. Subjects were patients with sepsis caused by pneumonia. PT and aPTT values, fibrinogen, and D-dimer levels was recorded from all sepsis patients then patients were observed until diagnosed decompensated or non-decompensated DIC, then the value of PT, aPTT, fibrinogen and D-dimer levels in the group of decompensated DIC and non-decompensated DIC were analysed. This study used cohort design. Subjects were 39 sepsis patients (58% with outcome decompensated DIC and 28 sepsis patients (42% with outcome non-decompensated DIC. From the hemostasis parameter test out, it was found that PT, aPTT, and fibrinogen were the predictor of decompensated DIC in patients with sepsis with relative risk 240.500, 7.157, and 6.421; respectively. Conclusions, prothrombin time, aPTT, fibrinogen are the test to know coagulation activation. Hemostasis parameter to predict decompensated DIC in sepsis patients are the shorten PT, aPTT, and the increased fibrinogen

  17. Metabolic Communication between Astrocytes and Neurons via Bicarbonate-Responsive Soluble Adenylyl Cyclase

    Choi, Hyun B.; Gordon, Grant R.J.; Zhou, Ning; Tai, Chao; Rungta, Ravi L.; Martinez, Jennifer; Milner, Teresa A.; Ryu, Jae K.; McLarnon, James G.; Tresguerres, Martin; Levin, Lonny R.; Buck, Jochen; MacVicar, Brian A.

    2012-01-01

    Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO3−) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response t...

  18. Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory.

    Alamgir, Kabir Md; Hojo, Yuko; Christeller, John T; Fukumoto, Kaori; Isshiki, Ryutaro; Shinya, Tomonori; Baldwin, Ian T; Galis, Ivan

    2016-02-01

    Plants defend against attack from herbivores by direct and indirect defence mechanisms mediated by the accumulation of phytoalexins and release of volatile signals, respectively. While the defensive arsenals of some plants, such as tobacco and Arabidopsis are well known, most of rice's (Oryza sativa) defence metabolites and their effectiveness against herbivores remain uncharacterized. Here, we used a non-biassed metabolomics approach to identify many novel herbivory-regulated metabolic signatures in rice. Most were up-regulated by herbivore attack while only a few were suppressed. Two of the most prominent up-regulated signatures were characterized as phenolamides (PAs), p-coumaroylputrescine and feruloylputrescine. PAs accumulated in response to attack by both chewing insects, i.e. feeding of the lawn armyworm (Spodoptera mauritia) and the rice skipper (Parnara guttata) larvae, and the attack of the sucking insect, the brown planthopper (Nilaparvata lugens, BPH). In bioassays, BPH insects feeding on 15% sugar solution containing p-coumaroylputrescine or feruloylputrescine, at concentrations similar to those elicited by heavy BPH attack in rice, had a higher mortality compared to those feeding on sugar diet alone. Our results highlight PAs as a rapidly expanding new group of plant defence metabolites that are elicited by herbivore attack, and deter herbivores in rice and other plants. © 2015 John Wiley & Sons Ltd.

  19. Diabetogenic action of streptozotocin: relationship of dose to metabolic response

    Junod, Alain; Lambert, André E.; Stauffacher, Werner; Renold, Albert E.

    1969-01-01

    The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections. PMID:4241908

  20. [Dissociation of antihypertensive and metabolic response to losartan and spironolactone in experimental rats with metabolic sindrome].

    Machado, Hussen; Pinheiro, Helady Sanders; Terra, Marcella Martins; Guerra, Martha de Oliveira; de Paula, Rogerio Baumgratz; Peters, Vera Maria

    2012-01-01

    The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. To assess the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan or Spironolactone from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II (Ang II) receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. The dissociation of the antihypertensive response to the blockades of Ang II receptors and mineralocorticoid indicates the involvement of Ang II in the pathogenesis of hypertension associated with obesity. Reduction of central obesity with Spironolactone suggests the presence of mineralocorticoid adipogenic effect.

  1. Supplementation of Saccharomyces cerevisiae modulates the metabolic response to lipopolysaccharide challenge in feedlot steers

    Live yeast has the potential to serve as an alternative to the use of low-dose supplementation of antibiotics in cattle due to the ability to alter ruminant metabolism; which in turn may influence the immune response. Therefore, the objective of this study was to determine the metabolic response to ...

  2. Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

    Malan, Nicolaas T; von Känel, Roland; Schutte, Alta E; Huisman, Hugo W; Schutte, Rudolph; Smith, Wayne; Mels, Carina M; Kruger, Ruan; Meiring, Muriel; van Rooyen, Johannes M; Malan, Leoné

    2013-10-12

    Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; pstress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels. © 2013.

  3. Acute metabolic response to fasted and postprandial exercise

    Lima FD

    2015-08-01

    Full Text Available Filipe Dinato de Lima,1,2 Ana Luiza Matias Correia,1 Denilson da Silva Teixeira,2 Domingos Vasco da Silva Neto,2 Ítalo Sávio Gonçalves Fernandes,2 Mário Boratto Xavier Viana,2 Mateus Petitto,2 Rodney Antônio da Silva Sampaio,2 Sandro Nobre Chaves,2 Simone Teixeira Alves,2 Renata Aparecida Elias Dantas,2 Márcio Rabelo Mota2 1University of Brasília, Brasília, DF, Brazil; 2Universitary Center of Brasília (UniCEUB, Brasília, DF, BrazilAbstract: The aim of this study was to analyze the acute metabolic response to exercise in fasting and postprandial. For this, ten individuals were submitted to an incremental treadmill test, with an initial speed of 5 and 1 km/h increments every minute, with no inclination, and a body composition assessment. After this 1st day, all volunteers were submitted to two experimental procedures (fasting and postprandial, with an aerobic exercise performed for 36 minutes at 65% of maximal oxygen consumption. At postprandial procedure, all subjects ingested a breakfast containing 59.3 g of carbohydrate (76.73%, 9.97 g of protein (12.90%, 8.01 g of lipids (10.37%, with a total energy intake of 349.17 kcal. An analysis of plasma concentration of triglycerides, lactate, and glucose was performed in two stages: before and after exercise. The Shapiro–Wilk test was used to verify the normality of the data. For analysis of glucose concentration, plasma lactate, and triglycerides, we used a repeated measures analysis of variance factorial 2×2, with Bonferroni multiple comparison test. The significance level of P<0.05 was adopted. The results indicated a maintenance level of glucose at fasting and a decrease in glucose concentration at postprandial exercise. Both conditions increase plasma lactate. Triglycerides also increased in the two experimental conditions; however, after exercise fasting, the increase was significantly higher than in the postprandial exercise. These data suggest that both exercises could increase

  4. Basal metabolic regulatory responses and rhythmic activity of ...

    ... Rattus sp. Low concentrations of kola nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate and amplitude of beat resulting, at still higher concentrations in heart failure. Keywords: Kolanut, extract, basal metabolic rate, mammalian heart ...

  5. Global patterns in lake ecosystem responses to warming based on the temperature dependence of metabolism.

    Kraemer, Benjamin M; Chandra, Sudeep; Dell, Anthony I; Dix, Margaret; Kuusisto, Esko; Livingstone, David M; Schladow, S Geoffrey; Silow, Eugene; Sitoki, Lewis M; Tamatamah, Rashid; McIntyre, Peter B

    2017-05-01

    Climate warming is expected to have large effects on ecosystems in part due to the temperature dependence of metabolism. The responses of metabolic rates to climate warming may be greatest in the tropics and at low elevations because mean temperatures are warmer there and metabolic rates respond exponentially to temperature (with exponents >1). However, if warming rates are sufficiently fast in higher latitude/elevation lakes, metabolic rate responses to warming may still be greater there even though metabolic rates respond exponentially to temperature. Thus, a wide range of global patterns in the magnitude of metabolic rate responses to warming could emerge depending on global patterns of temperature and warming rates. Here we use the Boltzmann-Arrhenius equation, published estimates of activation energy, and time series of temperature from 271 lakes to estimate long-term (1970-2010) changes in 64 metabolic processes in lakes. The estimated responses of metabolic processes to warming were usually greatest in tropical/low-elevation lakes even though surface temperatures in higher latitude/elevation lakes are warming faster. However, when the thermal sensitivity of a metabolic process is especially weak, higher latitude/elevation lakes had larger responses to warming in parallel with warming rates. Our results show that the sensitivity of a given response to temperature (as described by its activation energy) provides a simple heuristic for predicting whether tropical/low-elevation lakes will have larger or smaller metabolic responses to warming than higher latitude/elevation lakes. Overall, we conclude that the direct metabolic consequences of lake warming are likely to be felt most strongly at low latitudes and low elevations where metabolism-linked ecosystem services may be most affected. © 2016 John Wiley & Sons Ltd.

  6. Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.

    Eleanor C Saunders

    2014-01-01

    Full Text Available Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13C-stable isotope resolved metabolomics and (2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.

  7. The mechanical properties of dry, electrospun fibrinogen fibers

    Baker, Stephen; Sigley, Justin; Helms, Christine C. [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States); Stitzel, Joel [Department of Biomedical Engineering, Wake Forest University Health Sciences, Winston-Salem, NC, 27157 (United States); Berry, Joel; Bonin, Keith [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States); Guthold, Martin, E-mail: gutholdm@wfu.edu [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States)

    2012-02-01

    Due to their low immunogenicity, biodegradability and native cell-binding domains, fibrinogen fibers may be good candidates for tissue engineering scaffolds, drug delivery vehicles and other medical devices. We used a combined atomic force microscope (AFM)/optical microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in dry, ambient conditions. The AFM was used to stretch individual fibers suspended over 13.5 {mu}m wide grooves in a transparent substrate. The optical microscope, located below the sample, was used to monitor the stretching process. Electrospun fibrinogen fibers (diameter, 30-200 nm) can stretch to 74% beyond their original length before rupturing at a stress of 2.1 GPa. They can stretch elastically up to 15% beyond their original length. Using incremental stress-strain curves the viscoelastic behavior of these fibers was determined. The total stretch modulus was 4.2 GPa while the relaxed elastic modulus was 3.7 GPa. When held at constant strain, fibrinogen fibers display stress relaxation with a fast and slow relaxation time of 1.2 s and 11 s. In comparison to native and electrospun collagen fibers, dry electrospun fibrinogen fibers are significantly more extensible and elastic. In comparison to wet electrospun fibrinogen fibers, dry fibers are about 1000 times stiffer. - Highlights: Black-Right-Pointing-Pointer Fabricated dry, electrospun, fibrinogen fibers; average diameter, D{sub avg.} = 95 nm. Black-Right-Pointing-Pointer Determined mechanical properties with combined atomic force/optical microscope. Black-Right-Pointing-Pointer Fibers are very extensible ({epsilon}{sub max} = 74%) and elastic ({epsilon}{sub elastic} = 15%). Black-Right-Pointing-Pointer Fiber total modulus, E{sub tot.} = 4.2 GPa; elastic modulus, E{sub el.} = 3.7 GPa. Black-Right-Pointing-Pointer Fiber stress relaxation times: {tau}{sub 1} = 1.2 s and {tau}{sub 2} = 11 s.

  8. The mechanical properties of dry, electrospun fibrinogen fibers

    Baker, Stephen; Sigley, Justin; Helms, Christine C.; Stitzel, Joel; Berry, Joel; Bonin, Keith; Guthold, Martin

    2012-01-01

    Due to their low immunogenicity, biodegradability and native cell-binding domains, fibrinogen fibers may be good candidates for tissue engineering scaffolds, drug delivery vehicles and other medical devices. We used a combined atomic force microscope (AFM)/optical microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in dry, ambient conditions. The AFM was used to stretch individual fibers suspended over 13.5 μm wide grooves in a transparent substrate. The optical microscope, located below the sample, was used to monitor the stretching process. Electrospun fibrinogen fibers (diameter, 30–200 nm) can stretch to 74% beyond their original length before rupturing at a stress of 2.1 GPa. They can stretch elastically up to 15% beyond their original length. Using incremental stress–strain curves the viscoelastic behavior of these fibers was determined. The total stretch modulus was 4.2 GPa while the relaxed elastic modulus was 3.7 GPa. When held at constant strain, fibrinogen fibers display stress relaxation with a fast and slow relaxation time of 1.2 s and 11 s. In comparison to native and electrospun collagen fibers, dry electrospun fibrinogen fibers are significantly more extensible and elastic. In comparison to wet electrospun fibrinogen fibers, dry fibers are about 1000 times stiffer. - Highlights: ► Fabricated dry, electrospun, fibrinogen fibers; average diameter, D avg. = 95 nm. ► Determined mechanical properties with combined atomic force/optical microscope. ► Fibers are very extensible (ε max = 74%) and elastic (ε elastic = 15%). ► Fiber total modulus, E tot. = 4.2 GPa; elastic modulus, E el. = 3.7 GPa. ► Fiber stress relaxation times: τ 1 = 1.2 s and τ 2 = 11 s.

  9. Electrospun nanofibre fibrinogen for urinary tract tissue reconstruction

    McManus, Michael; Boland, Eugene; Sell, Scott; Bowen, Whitney; Koo, Harry; Simpson, David; Bowlin, Gary

    2007-01-01

    The purpose of this study was to demonstrate that human bladder smooth muscle cells (HBSM) remodel electrospun fibrinogen mats. Fibrinogen scaffolds were electrospun and disinfected using standard methods. Scaffolds were seeded with 5 x 10 4 HBSM per scaffold. Cultures were supplemented with aprotinin concentrations of 0 KIU ml -1 (no aprotinin), 100 KIU ml -1 or 1000 KIU ml -1 and incubated with twice weekly media changes. Samples were removed for evaluation at 1, 3, 7 and 14 days. Cultured scaffolds were evaluated with a WST-1 cell proliferation assay, scanning electron microscopy and histology. Cell culture demonstrated that HBSM readily migrated into and initiated remodelling of the electrospun fibrinogen scaffolds by deposition of collagen. Proliferation was suppressed during this initial phase with respect to a 2D control due to cell migration. Histology confirmed that proliferation increased during the later stages of remodelling. Remodelling was slower at higher aprotinin concentrations. These results demonstrate that HBSM rapidly remodel an electrospun fibrinogen scaffold and deposit native collagen. The process can be modulated using aprotinin, a protease inhibitor. These initial findings indicate that there is tremendous potential for electrospun fibrinogen as a urologic tissue engineering scaffold with the ultimate goal of producing an implantable acellular product that would promote cellular in-growth and in situ tissue regeneration

  10. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

    Hong Zhong

    2018-01-01

    Full Text Available In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

  11. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

    Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

    2018-01-01

    In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

  12. Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.

    Watson, Emma; MacNeil, Lesley T; Arda, H Efsun; Zhu, Lihua Julie; Walhout, Albertha J M

    2013-03-28

    Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Bone metabolism and hand grip strength response to aerobic versus ...

    porosis is incomplete and has prompted our interest to identify the type of effective osteogenic exercise. ... between aerobic and resistance exercise training in non-insulin dependent ... paired glucose metabolism on bone health as well as to.

  14. Metabolism

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  15. Metabolic and inflammatory responses to the common sweetener stevioside and a glycemic challenge in horses with equine metabolic syndrome.

    Elzinga, S E; Rohleder, B; Schanbacher, B; McQuerry, K; Barker, V D; Adams, A A

    2017-07-01

    Extracts derived from the leaves of the stevia plant (stevioside) are commonly used as sweeteners for humans and horses. Stevioside appears to be safe for human consumption, including for individuals with insulin dysregulation. In the horse, the safety or metabolic effects of stevioside on normal animals or on those with metabolic dysfunction are unknown. Furthermore, the inflammatory response to a glycemic challenge or to stevioside in horses is not well defined. Therefore, the objective of this study was to measure the effects of stevioside and a glycemic challenge on insulin, glucose, and inflammatory responses in horses with a common metabolic dysfunction (equine metabolic syndrome or EMS) compared with non-EMS controls. To accomplish this, 15 horses were selected; 8 EMS and 7 age-matched controls. An oral sugar test was performed using Karo corn syrup (karo) or stevioside in a random crossover design. Horses were given 0.15 mL/kg body weight of karo or its equivalent grams of sugar in stevia dissolved in water. Blood samples were collected by jugular venipuncture before administration of either stevia or karo and at 60 and 240 min after administration. Serum was used for glucose and insulin determination and plasma for isolation of peripheral blood mononuclear cells (PBMCs) for inflammatory cytokine analysis via flow cytometry and reverse transcription PCR (RT-PCR). Stevia appeared to stimulate lower glycemic and insulinemic responses when compared to karo, in particular in EMS horses. EMS and control horses had inverse inflammatory responses to administration of either stevia or karo with EMS horses having a proinflammatory response (P ≤ 0.05). These data provide evidence as to why horses with EMS may be predisposed to developing laminitis, potentially as a result of an exaggerated inflammatory response to glycemic and insulinemic responses. Furthermore, the data provide new avenues for exploring mechanisms behind the syndrome, in particular when using a

  16. The binding of fibrinogen to platelets in diabetes mellitus

    Minno, G. di; Cerbone, A.M.; Iride, C.; Mancini, M.

    1986-01-01

    Platelets from diabetics are known to be more sensitive in vitro to a variety of aggregating agents, to produce more prostaglandin endoperoxides and thromboxane and to bind more 125 I-fibrinogen than platelets from normal controls. Fibrinogen binding to platelets is a pre-requisite for platelet aggregation. Previous studies suggested a role for prostaglandins and/or thrombaxane A 2 in the exposure of fibrinogen receptors on platelets. The present study compares fibrinogen binding to hyperaggregable platelets from diabetic patients and to normal platelets when prostaglandin/thromboxane formation is suppressed by aspirin. It was found that pre-treatment with aspirin reduced collagen or thrombin-induced binding to platelets from none-retinopathic diabetics to the values seen in controls. By contrast, aspirin did not normalize binding to platelets obtained from retinopathic diabetics. The combination of aspirin with apyrase (an ADP scavenger) almost completely inhibited binding and aggregation of platelets from normal controls or non-retinophatic diabetics exposed to collagen or thrombin, whereas it only partially affected binding and aggregation of platelets from retinopathics. By using a monoclonal antibody (B59.2) to the platelet receptor for fibrinogen, we determined that this receptor was quantitatively and qualitatively the same on platelets from normal controls and diabetics. We conclude that increased fibrinogen binding and hyperaggregability of platelets from none-retinopathic diabetics is related to their capacity to form more prostaglandin endoperoxides/thromboxane than normal platelets. In contrast, hyperaggregability and increased binding of platelets from retinopathics appear at least partly related to a mechanism independent of ADP release and thromboxane synthesis. (Author)

  17. Climate Coping: Investigating Metabolic Responses in Crocosphaera watsonii

    Harris, K.

    2016-02-01

    Climate change causes chemical alterations in the open oceans, such as warming which leads to stratification, affecting nutrient ratios. Changes in nutrient ratios result in species shifts and a change in phytoplankton physiology, affecting all marine life. Unicellular diazotrophic microorganisms play a vital role in our open ocean ecosystems. These organisms do so by implementing metabolic processes that contribute to various availability of nutrients including; nitrogen and carbon. The open ocean diazotrophs are represented by multiple strains of Crocosphaera watsonii. The specific aim of this study was to determine whether the phenotype in small and large strain C. watsonii differs, in response to exposure to altered temperature gradients, measured as changes in cell density, photosynthetic efficiency, and EPS production. Triplicate cultures of C. watsonii WH8501 and C. watsonii WH0003 were inoculated into 60 ml of sterile Vineyard Sound SO media at a 1:10 ratio. Each culture was grown under; warm light levels (˜63 µ E m-2 s-1) on a 14:10 day/night cycle at temperatures of 27oC or 29oC. C. watsonii WH8501 cultures were harvested on Day 11, and C. watsonii WH0003 cultures were harvested on Day 9. To evaluate cell growth, fluorescence measurements were taken daily. Aliquots of experimental cultures were evaluated for cell density using flow-cytrometry, photosynthetic efficiency using FIRe fluorescence, and EPS production using a TEP determination assay. Proteins were extracted and analyzed by LC-MS-MS mass spectrometry. There was a correlation between temperature and EPS production for the two strains, C. watsonii WH8501 had a significantly higher growth rate when grown at 29oC, and a lower growth rate at 27oC compared to C. watsonii WH0003. Cultures grown at 27oC produced more EPS than those grown at 29oC. However, overall C. watsonii WH0003 produced more EPS than C. watsonii WH8501. We an increase in the yield of photosystem II (Fv/Fm) in C. watsonii WH0003 vs

  18. The metabolic response of Candida albicans to farnesol under hyphae-inducing conditions.

    Han, Ting-Li; Cannon, Richard D; Villas-Bôas, Silas G

    2012-12-01

    Farnesol is a quorum-sensing molecule (QSM) produced, and sensed, by the polymorphic fungus, Candida albicans. This cell-to-cell communication molecule is known to suppress the hyphal formation of C. albicans at high cell density. Despite many studies investigating the signalling mechanisms by which QSMs influence the morphogenesis of C. albicans, the downstream metabolic effect of these signalling pathways in response to farnesol-mediated morphogenesis remains obscure. Here, we have used metabolomics to investigate the metabolic response of C. albicans upon exposure to farnesol under hyphae-inducing conditions. We have found a general up-regulation of central carbon metabolic pathways when hyphal formation was suppressed by farnesol evidenced by a considerably larger number of central carbon metabolic intermediates detected under this condition at an overall lower intracellular level. By combining the metabolic profiles from farnesol-exposed cells with previous metabolomics data for C. albicans undergoing morphogenesis, we have identified several metabolic pathways that are likely to be associated with the morphogenetic process of C. albicans, as well as metabolic pathways such as those involved in lipid metabolism that appeared to be specifically affected by farnesol. Therefore, our results provide important new insights into the metabolic role of farnesol in C. albicans metabolism. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  19. Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

    de Moerloose, P; Schved, J-F; Nugent, D

    2016-07-01

    Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

  20. Extraction, radioiodination, and in vivo catabolism of equine fibrinogen

    Coyne, C.P.; Hornof, W.J.; Kelly, A.B.; O'Brien, T.R.; DeNardo, S.J.

    1985-01-01

    Equine fibrinogen was isolated and aliquots were stored frozen at -70 C before radiolabeling with 125I (half-life = 60.2 days; gamma = 35 keV, using monochloroiodine reagent. Radioiodination efficiencies were 49% to 53%, resulting in a labeled product with 98% protein-bound activity and 91% clottable radioactivity. In 6 equine in vivo investigations, plasma half-lives of 125I-labeled fibrinogen were from 4.1 to 5.2 days, corresponding to a mean daily plasma elimination rate of approximately 15%

  1. Whole-body CO2 production as an index of the metabolic response to sepsis

    Whole-body carbon dioxide (CO2) production (RaCO2) is an index of substrate oxidation and energy expenditure; therefore, it may provide information about the metabolic response to sepsis. Using stable isotope techniques, we determined RaCO2 and its relationship to protein and glucose metabolism in m...

  2. Metabolic imaging of tumor for diagnosis and response for therapy

    Zagaynova, Elena; Shirmanova, Marina; Lukina, Maria; Dudenkova, Varvara; Ignatova, Nadezgda; Elagin, Vadim; Shlivko, Irena; Scheslavsky, Vladislav; Orlinskay, Natalia

    2018-02-01

    Nonlinear optical microscopy combined with fluorescence lifetime imaging is a non-invasive imaging technique, based on the study of fluorescence decay times of naturally occurring fluorescent molecules, enabling a noninvasive investigation of the biological tissue with subcellular resolution. Cancer exhibits altered cellular metabolism, which affects the autofluorescence of metabolic cofactors NAD(P)H and FAD. In this study features of tumor metabolism in different systems of organization (from cell culture to patient lesion) was showed. The observed differences in the relative contributions of free NAD(P)H and FAD testify to an increased a glycolytic metabolism in cancer cells compare to fibroblasts. In 3D spheroids, the cells of the proliferating zone had greater a1 and lower tm values than the cells of the quiescent zone, which likely is a consequence of their higher glycolytic rate. During the growth of colorectal cancer in the experimental mouse model, the contribution of the free component of NAD(P)H was increased. Dysplastic nevus and melanoma is characterized by raised contribution of free NADH compare to healthy skin. Therefore, melanoma cells had very short value of τ1.

  3. Opposite metabolic responses of shoots and roots to drought

    Gargallo-Garriga, A.; Sardans, J.; Pérez-Trujillo, M.; Rivas-Ubach, A.; Oravec, Michal; Večeřová, Kristýna; Urban, Otmar; Jentsch, A.; Kreyling, J.; Beierkuhnlein, C.; Parella, T.; Penuelas, J.

    2014-01-01

    Roč. 4, č. 6829 (2014), s. 1-7 ISSN 2045-2322 Grant - others:AV ČR(CZ) M200871201 Institutional support: RVO:67179843 Keywords : shoot and roots * autotrophic and heterotrophic organs * environmental change * growth metabolism * water and nutirens Subject RIV: EH - Ecology, Behaviour Impact factor: 5.578, year: 2014

  4. Metabolic mapping of the brain's response to visual stimulation: studies in humans

    Phelps, M.E.; Kuhl, D.E.; Mazziotta, J.C.

    1981-01-01

    These studies demonstrated increasing glucose metabolic rates in the human primary (PVC) and associative (AVC) visual cortex as the complexity of visual scenes increased. The metabolic response of the AVC increased more rapidly with scene complexity than that of the PVC, indicating the greater involvement of the higher order AVC for complex visual interpretations. Increases in local metabolic activity by as much as a factor of 2 above that of control subjects with eyes closed indicate the wide range and metabolic reserve of the visual cortex

  5. Bacteroides gingivalis and Bacteroides intermedius recognize different sites on human fibrinogen

    Lantz, M.S.; Allen, R.D.; Bounelis, P.; Switalski, L.M.; Hook, M.

    1990-01-01

    Bacteroides (Porphyromonas) gingivalis and Bacteroides (Porphyromonas) intermedius have been implicated in the etiology of human periodontal diseases. These organisms are able to bind and degrade human fibrinogen, and these interactions may play a role in the pathogenesis of periodontal disease. In attempts to map the bacterial binding sites along the fibrinogen molecule, we have found that strains of B. gingivalis and B. intermedius, respectively, recognize spatially distant and distinct sites on the fibrinogen molecule. Isolated reduced and alkylated alpha-, beta-, and gamma-fibrinogen chains inhibited binding of 125I-fibrinogen to both Bacteroides species in a concentration-dependent manner. Plasmin fragments D and to some extent fragment E, however, produced a concentration-dependent inhibition of 125I-fibrinogen binding to B. intermedius strains but did not affect binding of 125I-fibrinogen to B. gingivalis strains. Radiolabeled fibrinogen chains and fragments were compared with 125I-fibrinogen with respect to specificity and reversibility of binding to bacteria. According to these criteria, gamma chain most closely resembled the native fibrinogen molecule in behavior toward B. gingivalis strains and fragments D most closely resembled fibrinogen in behavior toward B. intermedius strains. The ability of anti-human fibrinogen immunoglobulin G (IgG) to inhibit binding of 125I-fibrinogen to B. intermedius strains was greatly reduced by absorbing the IgG with fragments D. Absorbing the IgG with fragments D had no effect on the ability of the antibody to inhibit binding of 125I-fibrinogen to B. gingivalis strains. A purified staphylococcal fibrinogen-binding protein blocked binding of 125I-fibrinogen to B. intermedius strains but not to B. gingivalis strains

  6. Bacteroides gingivalis and Bacteroides intermedius recognize different sites on human fibrinogen

    Lantz, M.S.; Allen, R.D.; Bounelis, P.; Switalski, L.M.; Hook, M. (Univ. of Alabama, Birmingham (USA))

    1990-02-01

    Bacteroides (Porphyromonas) gingivalis and Bacteroides (Porphyromonas) intermedius have been implicated in the etiology of human periodontal diseases. These organisms are able to bind and degrade human fibrinogen, and these interactions may play a role in the pathogenesis of periodontal disease. In attempts to map the bacterial binding sites along the fibrinogen molecule, we have found that strains of B. gingivalis and B. intermedius, respectively, recognize spatially distant and distinct sites on the fibrinogen molecule. Isolated reduced and alkylated alpha-, beta-, and gamma-fibrinogen chains inhibited binding of 125I-fibrinogen to both Bacteroides species in a concentration-dependent manner. Plasmin fragments D and to some extent fragment E, however, produced a concentration-dependent inhibition of 125I-fibrinogen binding to B. intermedius strains but did not affect binding of 125I-fibrinogen to B. gingivalis strains. Radiolabeled fibrinogen chains and fragments were compared with 125I-fibrinogen with respect to specificity and reversibility of binding to bacteria. According to these criteria, gamma chain most closely resembled the native fibrinogen molecule in behavior toward B. gingivalis strains and fragments D most closely resembled fibrinogen in behavior toward B. intermedius strains. The ability of anti-human fibrinogen immunoglobulin G (IgG) to inhibit binding of 125I-fibrinogen to B. intermedius strains was greatly reduced by absorbing the IgG with fragments D. Absorbing the IgG with fragments D had no effect on the ability of the antibody to inhibit binding of 125I-fibrinogen to B. gingivalis strains. A purified staphylococcal fibrinogen-binding protein blocked binding of 125I-fibrinogen to B. intermedius strains but not to B. gingivalis strains.

  7. Genetic response to metabolic fluctuations: correlation between central carbon metabolism and DNA replication in Escherichia coli

    Szalewska-Pałasz Agnieszka

    2011-03-01

    Full Text Available Abstract Background Until now, the direct link between central carbon metabolism and DNA replication has been demonstrated only in Bacillus. subtilis. Therefore, we asked if this is a specific phenomenon, characteristic for this bacterium and perhaps for its close relatives, or a more general biological rule. Results We found that temperature-sensitivity of mutants in particular genes coding for replication proteins could be suppressed by deletions of certain genes coding for enzymes of the central carbon metabolism. Namely, the effects of dnaA46(ts mutation could be suppressed by dysfunction of pta or ackA, effects of dnaB(ts by dysfunction of pgi or pta, effects of dnaE486(ts by dysfunction of tktB, effects of dnaG(ts by dysfunction of gpmA, pta or ackA, and effects of dnaN159(ts by dysfunction of pta or ackA. The observed suppression effects were not caused by a decrease in bacterial growth rate. Conclusions The genetic correlation exists between central carbon metabolism and DNA replication in the model Gram-negative bacterium, E. coli. This link exists at the steps of initiation and elongation of DNA replication, indicating the important global correlation between metabolic status of the cell and the events leading to cell reproduction.

  8. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

    Wopereis, S.; Rubingh, C.M. de; Erk, M.J. van; Verheij, E.R.; Vliet, T. van; Cnubben, N.H.; Smilde, A.K.; Greef, J. van der; Ommen, B. van; Hendriks, H.F.

    2009-01-01

    BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one

  9. Metabolic Response to Food Restriction in Military-Eligible Women, with a Gender Comparison

    Young, Vernon

    1998-01-01

    Two major series of investigations are being undertaken to explore the metabolic responses of women who meet military standards for body-weight and percent body-fat to the nutritional stressors of food restriction...

  10. Metabolic Response to Food Restriction in Military-Eligible Women, With a Gender Comparison

    Young, Vernon

    1996-01-01

    Two major series of investigations will be undertaken to explore the metabolic responses of women, who meet military standards of body-weight and percent body-fat to the nutritional stressors of food restriction...

  11. Metabolic Response to Food Restriction in Military-Eligible Women, with a Gender Comparison

    Young, Vernon

    1997-01-01

    Two major series of investigations are being undertaken to explore the metabolic responses of women who meet military standards for body-weight and percent body-fat to the nutritional stressors of food restriction...

  12. Metabolic response of Candida albicans to phenylethyl alcohol under hyphae-inducing conditions.

    Han, Ting-Li; Tumanov, Sergey; Cannon, Richard D; Villas-Boas, Silas G

    2013-01-01

    Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs) identified in C. albicans. This extracellular signalling molecule inhibits the hyphal formation of C. albicans at high cell density. Little is known, however, about the underlying mechanisms by which this QSM regulates the morphological switches of C. albicans. Therefore, we have applied metabolomics and isotope labelling experiments to investigate the metabolic changes that occur in C. albicans in response to phenylethyl alcohol under defined hyphae-inducing conditions. Our results showed a global upregulation of central carbon metabolism when hyphal development was suppressed by phenylethyl alcohol. By comparing the metabolic changes in response to phenylethyl alcohol to our previous metabolomic studies, we were able to short-list 7 metabolic pathways from central carbon metabolism that appear to be associated with C. albicans morphogenesis. Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found in the majority of amino acids as well as in lactate and glyoxylate. However, isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the pyridine ring of NAD(+)/NADH and NADP(-/)NADPH molecules, showing that these nucleotides were the main products of phenylethyl alcohol catabolism. Interestingly, two metabolic pathways where these nucleotides play an important role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short-listed through our previous metabolomics works as metabolic pathways likely to be closely associated with C. albicans morphogenesis.

  13. 21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinogen/fibrin degradation products assay. 864.7320 Section 864.7320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....7320 Fibrinogen/fibrin degradation products assay. (a) Identification. A fibrinogen/fibrin degradation...

  14. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage - an observational study.

    Ahmed, S

    2012-10-01

    Fibrinogen replacement is critical in major obstetric haemorrhage (MOH). Purified, pasteurised fibrinogen concentrate appears to have benefit over cryoprecipitate in ease of administration and safety but is unlicensed in pregnancy. In July 2009, the Irish Blood Transfusion Service replaced cryoprecipitate with fibrinogen.

  15. Cardiovascular, hormonal and metabolic responses to graded exercise in juvenile diabetics with and without autonomic neuropathy

    Hilsted, J; Galbo, H; Christensen, N J

    1980-01-01

    Thirteen juvenile diabetics were studied in order to determine if decreased beat-to-beat variation during deep respiration, indicating abnormal autonomic nerve function, imply that cardiovascular, hormonal and metabolic responses are impaired. Patients with decreased beat-to-beat variation had to...... to be more heavily stressed during exercise to reach a certain heart rate or catecholamine level. The relation between other metabolic and hormonal response is discussed....

  16. Metabolic response to feeding in Tupinambis merianae: circadian rhythm and a possible respiratory constraint.

    Klein, Wilfried; Perry, Steven F; Abe, Augusto S; Andrade, Denis V

    2006-01-01

    The diurnal tegu lizard Tupinambis merianae exhibits a marked circadian variation in metabolism that is characterized by the significant increase in metabolism during part of the day. These increases in metabolic rate, found in the fasting animal, are absent during the first 2 d after meal ingestion but reappear subsequently, and the daily increase in metabolic rate is added to the increase in metabolic rate caused by digestion. During the first 2 d after feeding, priority is given to digestion, while on the third and following days, the metabolic demands are clearly added to each other. This response seems to be a regulated response of the animal, which becomes less active after food ingestion, rather than an inability of the respiratory system to support simultaneous demands at the beginning of digestion. The body cavity of Tupinambis is divided into two compartments by a posthepatic septum (PHS). Animals that had their PHS surgically removed showed no significant alteration in the postprandial metabolic response compared to tegus with intact PHS. The maximal metabolic increment during digestion, the relative cost of meal digestion, and the duration of the process were virtually unaffected by the removal of the PHS.

  17. Prognostic implications of plasma fibrinogen and serum C- reactive ...

    Key words: Plasma fibrinogen, serum C-reactive protein, biomarker, non-small cell lung cancer. Tropical Journal of Pharmaceutical Research ... demonstrated in colorectal [11], cervical, oesophageal [12], and pancreatic cancers .... demographic and clinical characteristic features of the patients involved are shown in Table ...

  18. Prognostic implications of plasma fibrinogen and serum Creactive ...

    Purpose: To investigate the prognostic implications of plasma fibrinogen and serum C-reactive protein (CRP) levels in tumour resection and survival following successful tumour resection in patients with nonsmall cell lung cancer (NSCLC). Methods: One hundred and fifty-three NSCLC patients who underwent surgical ...

  19. Use of labelled fibrinogen for the detection of phlebitis

    Serradimigni, A.; Mathieu, P.; Leonetti, J.; Sacerdote, P.; Bory, M.; Djiane, P.; Egre, A.

    The value of 125 I-labelled fibrinogen as a diagnostic tool in the detection of deep vein thrombosis is discussed. The results are compared to those obtained with phlebography and with the clinical symptomatology. The technical problems are described: examination method and interpretation [fr

  20. Study of some parameters of the fibrinogen - fibrin transformation reaction

    Hollard, D.; Suscillon, M.; Marcille, G.; Rambaud, F.; Baloyan, M.

    1966-01-01

    The authors studied the action of some parameters on the reaction of transformation fibrinogen-fibrin. The five parameters studied are: the concentration of substratum: a certain quantity of enzyme determines an optimum quantity of fibrinogen; the concentration of enzyme: a certain quantity of substratum defines an optimum quantity of enzyme, beyond which the excess of enzyme is unable to act, the substratum being saturated by the enzyme; the concentration of Ca ions: between 0,07 and 0,10 mg of Ca by mg of fibrinogen, the reaction appears with a great speed. Between 0,02 and 0,40 mg of Ca by mg of fibrinogen the fibrin stabilisation is possible, the FSF can act only inside the definite bounds; the ph of the solution: the reaction of the transformation appears with its maximum intensity on physiological ph, the polymerisation is not possible on acid ph; the temperature has an effect which could not really be verified owing to the fact that the technical realisation is difficult. (author) [fr

  1. Thrombus scintigraphy with Ga-67 DFO-DAS-Fibrinogen, 2

    Kawasaki, Yukiko

    1987-01-01

    In our previous in vivo study 67 Ga DFO-DAS-Fibrinogen was assessed for its usefulness as a radiopharmaceutical for the detection of thrombin in experimental animals (Report 1). The present study was undertaken to appraise the diagnostic value of 67 Ga DFO-DAS-Fibrinogen in human disease, especially in relation to blood coagulability as well as to thrombolytic drug regimen being given, in an effort to investigate its clinical applicability. Involved in this study were 48 patients with thrombosis proven by X-ray CT and other examinations. Of these 48, 42 had arterial thrombosis (20 with aortic aneurysm including the dissecting form, 11 in postoperative condition following vascular surgery with a prosthesis, 9 with intracardiac thrombosis accompanying heart disease, and 1 each with occlusive arteriosclerosis and cerebral infarction) and 6 had venous thrombosis. The 67 Ga DFO-DAS-Fibrinogen test proved to be positive in 55 % of arterial thrombin and in 50 % of venous thrombin. It is interesting to note that as high a positivity rate as 80 % was obtained for aortic aneurysm, although the positivity rate was disappointingly low for left atrial thrombin. No distinct correlation was noted to exist between the degree of accumulation of the tracer in thrombotic lesions and any of factors conceivably of clinical releavance, i.e. time elapsing from onset till testing, thrombolytic medication being given, and hematological factors. 67 Ga DFO-DAS-Fibrinogen appeared to be a radiodiagnostic agent that could possibly indicate the existing activity status of thrombosis. (author)

  2. 21 CFR 864.7340 - Fibrinogen determination system.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinogen determination system. 864.7340 Section 864.7340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7340...

  3. Prognostic implications of plasma fibrinogen and serum C- reactive ...

    reactive protein levels in non-small cell lung cancer resection and ... Abstract. Purpose: To investigate the prognostic implications of plasma fibrinogen and serum C-reactive protein ... The possibility of complete resection and associated findings are reported. Results: ... operable using pre-operative chemotherapy and/or ...

  4. Preparation and quality control of fibrinogen 99mTc

    Noto, M.G.; Rabiller, Graciela; Garrie Faget, Claudio; Fisman, Carlos; Manzini, Alberto

    1987-01-01

    A method of fibrinogen preparation is presented in order to label it with 99m Tc employing Sn as reducing agent in alkaline medium. Purity controls by chromatography, coagulation in rabbits and biodistribution in rats were performed. It is concluded that optimal time incubation is between 22 and 23 hs. (M.E.L.) [es

  5. MR imaging of metabolic white matter diseases: Therapeutic response

    Gebarski, S.S.; Allen, R.

    1987-01-01

    In metabolic diseases affecting the brain, MR imaging abnormalities include white-matter signal aberrations suggesting myelination delay, dysmyelination and demyelination, pathologic iron storage, and finally, loss of substance usually in a nonspecific pattern. The authors suggest that MR imaging may have therapeutic implications: (1) classic galactosemia - white-matter signal aberration became normal after dietary therapy; (2) phenylketonuria - age- and sex-matched treated and nontreated adolescents showed marked differences in brain volume, with the treated patient's volume nearly normal; (3) maple syrup urine disease - gross white-matter signal aberration became nearly normal after dietary therapy; and (4) hyperglycinemia - relentless progression of white-matter signal aberration and loss of brain substance despite therapy. These data suggest that brain MR imaging may provide a therapeutic index in certain metabolic diseases

  6. Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses.

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2017-08-01

    Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Chronic myeloid leukemia patients sensitive and resistant to imatinib treatment show different metabolic responses.

    Jiye A

    Full Text Available The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML. However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML and patients resistant to imatinib (RCML had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA. In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention.

  8. Metabolism

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  9. Risk Factors for Postoperative Fibrinogen Deficiency after Surgical Removal of Intracranial Tumors.

    Naili Wei

    Full Text Available Higher levels of fibrinogen, a critical element in hemostasis, are associated with increased postoperative survival rates, especially for patients with massive operative blood loss. Fibrinogen deficiency after surgical management of intracranial tumors may result in postoperative intracranial bleeding and severely worsen patient outcomes. However, no previous studies have systematically identified factors associated with postoperative fibrinogen deficiency. In this study, we retrospectively analyzed data from patients who underwent surgical removal of intracranial tumors in Beijing Tiantan Hospital date from 1/1/2013to12/31/2013. The present study found that patients with postoperative fibrinogen deficiency experienced more operative blood loss and a higher rate of postoperative intracranial hematoma, and they were given more blood transfusions, more plasma transfusions, and were administered larger doses of hemocoagulase compared with patients without postoperative fibrinogen deficiency. Likewise, patients with postoperative fibrinogen deficiency had poorer extended Glasgow Outcome Scale (GOSe, longer hospital stays, and greater hospital expenses than patients without postoperative fibrinogen deficiency. Further, we assessed a comprehensive set of risk factors associated with postoperative fibrinogen deficiency via multiple linear regression. We found that body mass index (BMI, the occurrence of postoperative intracranial hematoma, and administration of hemocoagulasewere positively associated with preoperative-to-postoperative plasma fibrinogen consumption; presenting with a malignant tumor was negatively associated with fibrinogen consumption. Contrary to what might be expected, intraoperative blood loss, the need for blood transfusion, and the need for plasma transfusion were not associated with plasma fibrinogen consumption. Considering our findings together, we concluded that postoperative fibrinogen deficiency is closely associated with

  10. Dealing with hunger: Metabolic stress responses in tumors

    Michael A Reid

    2013-01-01

    Full Text Available Increased nutrient uptake and usage is a hallmark of many human malignancies. During the course of tumorigenesis, cancer cells often outstrip their local nutrient supply leading to periods of nutrient deprivation. Interestingly, cancer cells often develop strategies to adapt and survive these challenging conditions. Accordingly, understanding these processes is critical for developing therapies that target cancer metabolism. Exciting new progress has been made in elucidating the mechanisms used by cancer cells under nutrient restricted conditions. In this review, we highlight recent studies that have brought insight into how cancer cells deal with low nutrient environments.

  11. Metabolic development of the porcine placenta in response to alterations in maternal or fetal homeostasis

    Namsey, T.G.; kasser, T.R.; Hausman, G.J.; Martin, R.J.

    1986-01-01

    Porcine placenta has been utilized as a model for elucidating contributions of both fetal and maternal tissues to metabolic activity of the placenta in response to a variety of stresses. Alloxan diabetes, food restriction and genetic obesity all produced alterations in placental metablolism with differences in responses of fetal and maternal placentas. Further analysis of nutrient untilization by the placenta produced dramatic differences in the partitioning of substrates by fetal and maternal tissues during placental development. Metabolic activity of maternal tissue contributed to overall placental metabolic activity to a greater degree than fetal tissue. However, experiments with in utero fetal decapitation indicated that some of differences between fetal and maternal placental metabolic activity may be due to the influence of fetal regulatory mechanisms. Maternal endometrium plays a critical role in metabolic response of uteroplacenta and thus availability of nutrients to the fetus and fetal placenta. Differences in metabolic development of fetal and maternal tissues suggested that regulation of placental metabolism may originate from fetal as well as maternal sources

  12. Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats.

    Hamelink, C R; Currie, P J; Chambers, J W; Castonguay, T W; Coscina, D V

    1994-09-01

    Glucocorticoids are important in influencing substrate flux through the metabolic pathways. This study was designed to answer the question "Does adrenalectomy (ADX) cause a shift toward fat metabolism as measured by a decrease in respiratory quotient (RQ)?" Male Sprague-Dawley rats were divided into four groups, ADX, ADX + 20% corticosterone (Cort) (ADX-20%), ADX + 40% Cort (ADX-40%), or sham-operated controls (Sham). ADX-20% received 50 mg and ADX-40% 100 mg Cort dissolved in 250-mg cholesterol pellets and placed subcutaneously. Each rat was monitored for 90 min four times both during a preoperative period and again after a 1-wk postsurgical recovery period in an indirect calorimeter. Cort prevented ADX-induced suppression of weight gain and food intake. ADX decreased motoric activity in both the light and dark periods. Cort restored activity to Sham levels. ADX decreased RQ only in the dark (0.858 ADX vs. 0.891 Sham) and was reversed only in the ADX-40% group. Energy expenditure (EE) was depressed in both the light and dark by ADX; Cort partially restored EE to Sham values in the light period.

  13. Behaviour of homologous 125I fibrinogen after thrombin and ancrod infusion in rabbits

    Setter, R.

    1977-01-01

    The behaviour of radioactively labelled fibrinogen after infusion of thrombin or ancrod is investigated. Common factors and differences in the behaviour of fibrinogen after infusion of these two enzymes, which act proteolytically on the fibrinogen, are dealt with. Rabbits received an i.v. injection of homologous 125 I-fibrinogen 3 days before ancrod or thrombin infusion. On the day of the experiments, one group of animals received an ancrod infusion (1.5 U/kg body weight for 30 minutes), the other a thrombin infusion (600 U/kg body weight for 60 minutes). Intravenous ancrod and thrombin infusions lowered the fibrinogen level to 30% or 50% of the initial value due to intravascular coagulation. About 50% of the 125 I fibrinogen was transformed after ancrod exposure into a non-coagulating fraction of fibrinogen derivatives which produces no fibrinolytic decomposition products. (orig./AJ) [de

  14. Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring

    Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

    2017-01-01

    Background The mother?s consumption of high-fat food can affect glucose metabolism and the hypothalamic?pituitary?adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Methods Female rats were randomly divided into normal and high-fat diet groups and were fed in a...

  15. Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

    Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M.

    1991-01-01

    Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37 degree C. A functional fibrinogen-binding component (M r , 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with 125 I-fibrinogen. Fibrinogen degradation did not occur at 4 degree C but did occur at 22 and 37 degree C. When bacteria and iodinated fibrinogen were incubated at 37 degree C, two major fibrinogen fragments (M r , 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M r , 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M r -120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-α-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate

  16. Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

    Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M. (Univ. of Alabama at Birmingham (USA))

    1991-01-01

    Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37{degree}C. A functional fibrinogen-binding component (M{sub r}, 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with {sup 125}I-fibrinogen. Fibrinogen degradation did not occur at 4{degree}C but did occur at 22 and 37{degree}C. When bacteria and iodinated fibrinogen were incubated at 37{degree}C, two major fibrinogen fragments (M{sub r}, 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M{sub r}, 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M{sub r}-120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-{alpha}-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate.

  17. Time-dependent association between platelet-bound fibrinogen and the Triton X-100 insoluble cytoskeleton

    Peerschke, E.I.

    1991-01-01

    Previous studies indicated a correlation between the formation of EDTA-resistant (irreversible) platelet-fibrinogen interactions and platelet cytoskeleton formation. The present study explored the direct association of membrane-bound fibrinogen with the Triton X-100 insoluble cytoskeleton of aspirin-treated, gel-filtered platelets, activated but not aggregated with 20 mumol/L adenosine diphosphate (ADP) or 150 mU/mL human thrombin (THR) when bound fibrinogen had become resistant to dissociation by EDTA. Conversion of exogenous 125I-fibrinogen to fibrin was prevented by adding Gly-Pro-Arg and neutralizing THR with hirudin before initiating binding studies. After 60 minutes at 22 degrees C, the cytoskeleton of ADP-treated platelets contained 20% +/- 12% (mean +/- SD, n = 14) of membrane-bound 125I-fibrinogen, representing 10% to 50% of EDTA-resistant fibrinogen binding. The THR-activated cytoskeleton contained 45% +/- 15% of platelet bound fibrinogen, comprising 80% to 100% of EDTA-resistant fibrinogen binding. 125I-fibrinogen was not recovered with platelet cytoskeletons if binding was inhibited by the RGDS peptide, excess unlabeled fibrinogen, or disruption of the glycoprotein (GP) IIb-IIIa complex by EDTA-treatment. Both development of EDTA-resistant fibrinogen binding and fibrinogen association with the cytoskeleton were time dependent and reached maxima 45 to 60 minutes after fibrinogen binding to stimulated platelets. Although a larger cytoskeleton formed after platelet stimulation with thrombin as compared with ADP, no change in cytoskeleton composition was noted with development of EDTA-resistant fibrinogen binding

  18. Dietary fatty acids linking postprandial metabolic response and chronic diseases.

    Ortega, Almudena; Varela, Lourdes M; Bermudez, Beatriz; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2012-01-01

    Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.

  19. Response to Cardiac Resynchronization Therapy: The Muscular Metabolic Pathway

    Jérémie Jaussaud

    2011-01-01

    245±140 seconds (=.01. Peak VO2, VE/VCO2, peak circulatory power and NYHA were improved after CRT (13±4 to16±5 ml/kg/min (<.05, 45±16 to 39±13 (<.01, 1805±844 to 2225±1171 mmHg.ml/kg/min (<.01 and 3±0.35 to 1.88±0.4 (=.01. In addition, left ventricular ejection fraction and end-systolic volumes were improved from 24±8 to 29±7% (<.01 and from 157±69 to 122±55 ml (<.01. Conclusion. We suggest that CRT leads to an increase in oxidative muscular metabolism and postponed anaerobic threshold reducing exaggerated hyperventilation during exercise.

  20. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    Kim, Hyerang; Lee, Saningun; Choue, Ryowon

    2011-01-01

    Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collec...

  1. Diagnostic value of radioactive fibrinogen and rheography in phlebitis

    Serradimigni, A.; Bory, M.; Djiane, P.; Sacerdote, P.; Mathieu, P.; Leonetti, J.; Egre, A.

    1975-01-01

    In 212 patients the diagnostic value of radioactive fibrinogen and rheography in deep venous thrombosis in the leg was studied by comparing the results from these two methods with phlebography. Radioactive fibrinogen seems the better means of diagnosis in early distal phlebitis. However, the method is expensive, the radioactive substance can only be manipulated in certain specialized centers, and is useless in the presence of hematoma. Rheography is less expensive, more easily manipulated, yet less sensitive as only proximal phlebitis can be detected especially when completely occlusive. In addition, active patient cooperation is necessary. The time needed to realize the two methods is a major obstacle; however, they can be fruitful if integrated into a specialized department for the diagnosis and treatment of thrombo-embolic disease [fr

  2. The role of fibrinogen and haemostatic assessment in postpartum haemorrhage

    Wikkelsø, Anne Juul

    2015-01-01

    Pregnancy is a state of hypercoagulobility that might be an evolutionary way of protecting parturients from exsanguination following child birth. Observational studies suggest an association between a low level of fibrinogen (coagulation factor I) at the start of postpartum haemorrhage (PPH....... Paper III was based on two national Danish registries evaluating the predictability of postpartum blood transfusion. Prediction was found difficult. However, retained placental parts seemed to be the strongest predictor. Since this diagnosis is made very late and often in association with the onset...... describes the protocol for a RCT of early fibrinogen supplementation in women with severe postpartum haemorrhage. Several practical, ethical and trial management challenges need to be addressed when conducting independent clinical research involving parturients with severe bleeding, placebo...

  3. Preparation of 99 sup(m)Tc labeled fibrinogen

    Almeida, M.A.T.M. de; Silva, C.P.G. da.

    1984-01-01

    A simple method for the preparation of 99 sup(m) TC labelled Fibrinogen using stannous chloride as reducing agent of 99 sup(m) TcO- 4 ion is presented. A sample of 20 mg of Fibrinogen is dissolved in 2 ml of buffer carbonate (pH=8) and 0.3 ml stannous chloride 0.2% is added. A sterile solution of sodium pertechnetate 99 sup(m) Tc eluted from a Mo-Tc generator is immediately added. The mixture rests for 30 minutes and after this period, the obtained yield is about 70%. The lyophilized kits also presented a yield of 70%, being therefore suitable for medical applications. (Author) [pt

  4. Endocrine, metabolic and cardiovascular responses to adrenaline after abdominal surgery

    Hilsted, J; Wilken-Jensen, Charlotte; Birch, K

    1990-01-01

    Adrenaline-induced changes in heart rate, blood pressure, plasma adrenaline and noradrenaline, cortisol, glucagon, insulin, cAMP, glucose lactate, glycerol and beta-hydroxybutyrate were studied preoperatively and 4 and 24 h after skin incision in 8 patients undergoing elective cholecystectomy. Late...... postoperative responses of blood glucose, plasma cAMP, lactate and glycerol to adrenaline infusion were reduced, whereas other responses were unaffected. Blood glucose appearance and disappearance rate as assessed by [3H]3-glucose infusion was unchanged pre- and postoperatively. The increase in glucose...... appearance rate following adrenaline was similar pre- and postoperatively. These findings suggest that several beta-receptor-mediated responses to adrenaline are reduced after abdominal surgery....

  5. Clotting of mammalian fibrinogens by papain: A re-examination

    Doolittle, RF

    2014-01-01

    © 2014 American Chemical Society. Papain has long been known to cause the gelation of mammalian fibrinogens. It has also been reported that papain-fibrin is insoluble in dispersing solvents like strong urea or sodium bromide solutions, similar to what is observed with thrombin-generated clots in the presence of factor XIIIa and calcium. In those old studies, both the gelation and subsequent clot stabilization were attributed to papain, although the possibility that the second step might be du...

  6. The cross-tissue metabolic response of abalone (Haliotis midae) to functional hypoxia.

    Venter, Leonie; Loots, Du Toit; Mienie, Lodewyk J; Jansen van Rensburg, Peet J; Mason, Shayne; Vosloo, Andre; Lindeque, Jeremie Z

    2018-03-23

    Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone ( Haliotis midae) subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids) for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

  7. The cross-tissue metabolic response of abalone (Haliotis midae to functional hypoxia

    Leonie Venter

    2018-03-01

    Full Text Available Functional hypoxia is a stress condition caused by the abalone itself as a result of increased muscle activity, which generally necessitates the employment of anaerobic metabolism if the activity is sustained for prolonged periods. With that being said, abalone are highly reliant on anaerobic metabolism to provide partial compensation for energy production during oxygen-deprived episodes. However, current knowledge on the holistic metabolic response for energy metabolism during functional hypoxia, and the contribution of different metabolic pathways and various abalone tissues towards the overall accumulation of anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue samples indicated that South African abalone (Haliotis midae subjected to functional hypoxia utilises predominantly anaerobic metabolism, and depends on all of the main metabolite classes (proteins, carbohydrates and lipids for energy supply. Functional hypoxia caused increased levels of anaerobic end-products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation in arginine levels was detected, confirming that abalone use phosphoarginine to generate energy during functional hypoxia. Different tissues showed varied metabolic responses to hypoxia, with functional hypoxia showing excessive changes in the adductor muscle and gills. From this metabolomics investigation, it becomes evident that abalone are metabolically able to produce sufficient amounts of energy when functional hypoxia is experienced. Also, tissue interplay enables the adjustment of H. midae energy requirements as their metabolism shifts from aerobic to anaerobic respiration during functional hypoxia. This article has an associated First Person interview with the first author of the paper.

  8. Laser-assisted fibrinogen bonding of umbilical vein grafts.

    Oz, M C; Williams, M R; Souza, J E; Dardik, H; Treat, M R; Bass, L S; Nowygrod, R

    1993-06-01

    Despite success with autologous tissue welding, laser welding of synthetic vascular prostheses has not been possible. The graft material appears inert and fails to allow the collagen breakdown and electrostatic bonding that results in tissue welding. To develop a laser welding system for graft material, we repaired glutaraldehyde-tanned human umbilical cord vein graft incisions using laser-assisted fibrinogen bonding (LAFB) technology. Modified umbilical vein graft was incised transversely (1.2 cm). Incisions were repaired using sutures, laser energy alone, or LAFB. For LAFB, indocyanine green dye was mixed with human fibrinogen and the compound applied with forceps onto the weld site prior to exposure to 808 nm diode laser energy (power density 4.8 W/cm 2). Bursting pressures for sutured repairs (126.6 +/- 23.4 mm Hg) were similar to LAFB anastomoses (111.6 +/- 55.0 mm Hg). No evidence of collateral thermal injury to the graft material was noted. In vivo evaluation of umbilical graft bonding with canine arteries demonstrates that LAFB can reliably reinforce sutured anastomoses. The described system for bonding graft material with laser exposed fibrinogen may allow creation or reinforcement of vascular anastomoses in procedures where use of autologous tissue is not feasible.

  9. Clinical applications of Ga-67 DFO-DAS-fibrinogen

    Iio, Masahiro; Ohtake, Tohru; Nishikawa, Junichi; Watanabe, Toshiaki; Yasuhara, Hiroshi; Ohashi, Shigenobu; Takayama, Yutaka; Tada, Yusuke; Shirakawa, Motoaki

    1987-01-01

    Ga-67 DFO-DAS-fibrinogen scanning was performed in 15 patients to detect fresh arterial thrombus. Seven patients were preoperative cases of aortic aneurysm and eight were postoperative cases of graft bypass. Scanning was performed on the first and second days after the injection. Nine of 13 grafts in eight cases were visualized by 67 Ga-DFO-DAS-fibrinogen scan. Velour Dacron grafts were more strongly visualized compared with woven Dacron or Goatex. In three patients with aortic aneurysm in whom fresh thrombus was identified by operative findings, arterial thrombus was clearly visualized by 67 Ga-DFO-DAS-fibrinogen scan, whereas in three other patients with aortic aneurysm, thrombus was not visualized, although it was identified by other examinations. In one case, a marked accumulation was observed in the abdominal aorta, although no arterial thrombus was found at operation. This was thought to be an accumulation in a blood pool because it decreased on the second day. We think it important to observe the relative changes of accumulation. (author)

  10. Fibrinogen titer and glycemic status in women using contraceptives

    Syed, S.; Qureshi, M.A.

    2002-01-01

    Objective: To assess the coagulation and glycemic status in Pakistani women using contraceptives. Design: The study was conducted prospectively on 70 women and compared with 10 age-matched controls. Place and Duration of Study: The study was conducted at Karachi. Period of study was 18 month. Subjects and Methods: Eighty women aged between 20-45 years selected from low socioeconomic class and poor family background were categorized in control (n=10) and oral and injectable contraceptive users (n = 70). The contraceptives used were tablet Lofemenal, injection Norigest and Norplant implant. Their blood was tested for fibrinogen titer and random blood glucose. Results: There was no appreciable difference either in fibrinogen titer or plasma glucose levels in injectable users as compared to controls, but increased incidence of high fibrinogen titer and borderline blood glucose was observed in oral contraceptive users 25% and 20 % respectively. Conclusion: It was concluded that long-term use of oral contraceptives (> 3 years) might increase the thrombotic tendency and elevate the plasma glucose levels especially in women above 30 years of age. (author)

  11. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

    Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

    2015-01-01

    Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... in the form of oxidative stress, has been linked to a wide variety of diseases including inborn errors of metabolism. In this review we will summarize how the functional state of mitochondria -- and especially the concentration of reactive oxygen species (ROS), produced in connection with the respiratory...... chain -- regulates cellular stress responses by redox regulation of nuclear gene networks involved in repair systems to maintain cellular homeostasis and health. Based on our own and other's studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism...

  12. Irisin in response to exercise in humans with and without metabolic syndrome.

    Huh, Joo Young; Siopi, Aikaterina; Mougios, Vassilis; Park, Kyung Hee; Mantzoros, Christos S

    2015-03-01

    Irisin is a recently identified exercise-induced myokine. However, the circulating levels of irisin in response to different types of exercise in subjects with metabolic syndrome are unknown. This study aimed to study the levels of irisin in healthy males and subjects with metabolic syndrome at baseline and in response to exercise. Each individual completed high-intensity interval exercise (HIIE), continuous moderate-intensity exercise (CME), and resistance exercise (RE) sessions in a random, crossover design. Percentage change in circulating irisin levels was examined. Two different irisin assays were used to compare the results of the RE study. Circulating irisin increased immediately after HIIE, CME, and RE and declined 1 hour later. The increase was greater in response to resistance compared with either high-intensity intermittent exercise or CME. Change in irisin in response to exercise did not differ between individuals with and without metabolic syndrome. Exercise is able to increase circulating irisin levels in individuals with the metabolic syndrome as well as healthy individuals. Whether this increase may contribute to the beneficial effects of exercise on patients with the metabolic syndrome remains to be studied further.

  13. Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders.

    Fenger-Eriksen, Christian; Moore, Gary W; Rangarajan, Savita; Ingerslev, Jørgen; Sørensen, Benny

    2010-12-01

    Measurement of plasma fibrinogen is often required in critically ill patients or massively bleeding patients being resuscitated with colloid plasma expander. This study aimed at evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated significantly higher in plasma diluted with colloid plasma expander compared with isotonic saline. Fibrinogen measurements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo-optical Clauss methods, one mechanical Clauss method, a prothrombin-derived method, and viscoelastic measurement through thromboelastometry. Measurement of fibrinogen levels was significantly different when performed on alternate analytical platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo-optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin. This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss. © 2010 American Association of Blood Banks.

  14. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Nolte, Marc W. [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Solomon, Cristina [CSL Behring GmbH, Medical Affairs, Marburg (Germany); Department of Anaesthesiology, Perioperative Medicine and General Intensive Care, Paracelsus Medical University, Salzburg (Austria); Herzog, Eva; Dickneite, Gerhard [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany)

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  15. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-01-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  16. Organ-specific metabolic responses to drought in Pinus pinaster Ait.

    de Miguel, Marina; Guevara, M Ángeles; Sánchez-Gómez, David; de María, Nuria; Díaz, Luis Manuel; Mancha, Jose A; Fernández de Simón, Brígida; Cadahía, Estrella; Desai, Nalini; Aranda, Ismael; Cervera, María-Teresa

    2016-05-01

    Drought is an important driver of plant survival, growth, and distribution. Water deficit affects different pathways of metabolism, depending on plant organ. While previous studies have mainly focused on the metabolic drought response of a single organ, analysis of metabolic differences between organs is essential to achieve an integrated understanding of the whole plant response. In this work, untargeted metabolic profiling was used to examine the response of roots, stems, adult and juvenile needles from Pinus pinaster Ait. full-sib individuals, subjected to a moderate and long lasting drought period. Cyclitols content showed a significant alteration, in response to drought in all organs examined, but other metabolites increased or decreased differentially depending on the analyzed organ. While a high number of flavonoids were only detected in aerial organs, an induction of the glutathione pathway was mainly detected in roots. This result may reflect different antioxidant mechanisms activated in aerial organs and roots. Metabolic changes were more remarkable in roots than in the other organs, highlighting its prominent role in the response to water stress. Significant changes in flavonoids and ascorbate metabolism were also observed between adult and juvenile needles, consistent with previously proven differential functional responses between the two developmental stages. Genetic polymorphisms in candidate genes coding for a Myb1 transcription factor and a malate dehydrogenase (EC 1.1.1.37) were associated with different concentration of phenylalanine, phenylpropanoids and malate, respectively. The results obtained will support further research on metabolites and genes potentially involved in functional mechanisms related to drought tolerance in trees. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Jasmonate-responsive transcription factors regulating plant secondary metabolism.

    Zhou, Meiliang; Memelink, Johan

    2016-01-01

    Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. [Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-04

    Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem.

  19. Cytolytic T lymphocyte responses to metabolically inactivated stimulator cells. I. Metabolic inactivation impairs both CD and LD antigen signals

    Kelso, A.; Boyle, W.

    1982-01-01

    The effects of metabolic inactivation of spleen cells on antigen presentation to precursors of alloreactive cytolytic T lymphocytes (T/sub c/) were examined. By serological methods, populations inactivated by ultraviolet irradiation, glutaraldehyde fixation or plasma membrane isolation were found to retain normal levels of H-2K/D and Ia antigens. However, comparison of the antigen doses required to stimulate secondary T/sub c/ responses in mixed leukocyte culture showed that the inactivated preparations were approximately 10-fold less immunogenic than X-irradiated spleen cells. Their total inability to stimulate primary cytolytic responses pointed to at least a 100-fold impairment of immunogenicity for unprimed T/sub c/ precursors in the case of uv-irradiated and glutaraldehyde-treated stimulator cells, and at least a 10-fold impairment for membrane fragments. Experiments showing that the capacity of cell monolayers to absorb precursor T/sub c/ from unprimed spleen populations was reduced following uv-irradiation or glutaraldehyde treatment provided direct evidence that this loss of immunogenicity was due in part to suboptimal antigen presentation to precursor T/sub c/. It is concluded that, in addition to the traditional view that these treatments damage the ''LD'' signal to helper T lymphocytes, metabolic inactivation also impairs recognition of ''CD'' determinants by precursor T/sub c/

  20. Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization.

    Valeriy Demchev

    Full Text Available Fibrinogen like protein 1(Fgl1 is a secreted protein with mitogenic activity on primary hepatocytes. Fgl1 is expressed in the liver and its expression is enhanced following acute liver injury. In animals with acute liver failure, administration of recombinant Fgl1 results in decreased mortality supporting the notion that Fgl1 stimulates hepatocyte proliferation and/or protects hepatocytes from injury. However, because Fgl1 is secreted and detected in the plasma, it is possible that the role of Fgl1 extends far beyond its effect on hepatocytes. In this study, we show that Fgl1 is additionally expressed in brown adipose tissue. We find that signals elaborated following liver injury also enhance the expression of Fgl1 in brown adipose tissue suggesting that there is a cross talk between the injured liver and adipose tissues. To identify extra hepatic effects, we generated Fgl1 deficient mice. These mice exhibit a phenotype suggestive of a global metabolic defect: Fgl1 null mice are heavier than wild type mates, have abnormal plasma lipid profiles, fasting hyperglycemia with enhanced gluconeogenesis and exhibit differences in white and brown adipose tissue morphology when compared to wild types. Because Fgl1 shares structural similarity to Angiopoietin like factors 2, 3, 4 and 6 which regulate lipid metabolism and energy utilization, we postulate that Fgl1 is a member of an emerging group of proteins with key roles in metabolism and liver regeneration.

  1. Metabolic responses in Candida tropicalis to complex inhibitors during xylitol bioconversion.

    Wang, Shizeng; Li, Hao; Fan, Xiaoguang; Zhang, Jingkun; Tang, Pingwah; Yuan, Qipeng

    2015-09-01

    During xylitol fermentation, Candida tropicalis is often inhibited by inhibitors in hemicellulose hydrolysate. The mechanisms involved in the metabolic responses to inhibitor stress and the resistances to inhibitors are still not clear. To understand the inhibition mechanisms and the metabolic responses to inhibitors, a GC/MS-based metabolomics approach was performed on C. tropicalis treated with and without complex inhibitors (CI, including furfural, phenol and acetic acid). Partial least squares discriminant analysis was used to determine the metabolic variability between CI-treated groups and control groups, and 25 metabolites were identified as possible entities responsible for the discrimination caused by inhibitors. We found that xylose uptake rate and xylitol oxidation rate were promoted by CI treatment. Metabolomics analysis showed that the flux from xylulose to pentose phosphate pathway increased, and tricarboxylic acid cycle was disturbed by CI. Moreover, the changes in levels of 1,3-propanediol, trehalose, saturated fatty acids and amino acids showed different mechanisms involved in metabolic responses to inhibitor stress. The increase of 1,3-propanediol was considered to be correlated with regulating redox balance and osmoregulation. The increase of trehalose might play a role in protein stabilization and cellular membranes protection. Saturated fatty acids could cause the decrease of membrane fluidity and make the plasma membrane rigid to maintain the integrity of plasma membrane. The deeper understanding of the inhibition mechanisms and the metabolic responses to inhibitors will provide us with more information on the metabolism regulation during xylitol bioconversion and the construction of industrial strains with inhibitor tolerance for better utilization of bioresource. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Fibrinogen function is impaired in whole blood from patients with cyanotic congenital heart disease

    Jensen, A S; Johansson, Pär I.; Bochsen, Louise

    2013-01-01

    haemoptysis. METHODS: In a prospective study 75 adult CCHD patients had haematocrit, platelet count, and plasma fibrinogen concentration examined. Furthermore thrombelastography(TEG) as well as TEG Functional Fibrinogen(TEG FF) assay evaluating fibrinogen function(FLEV) was performed. Data were compared...... with historical data regarding previous haemoptysis in CCHD patients. RESULTS: Haematocrit was 57±8% and platelet counts in the lower normal range. TEG revealed a hypocoagulable condition with impaired clot formation. TEG values were correlated to haematocrit, indicating that elevated haematocrit causes impaired....... CONCLUSION: Patients with CCHD are hypocoagulable mainly due to impaired fibrinogen function. Despite a low platelet count, platelet function does not seem to be severely affected in CCHD patients. Haemostasis, and especially fibrinogen function, is negatively affected by elevated haematocrit, and fibrinogen...

  3. Role of the Mixed-Lineage Protein Kinase Pathway in the Metabolic Stress Response to Obesity

    Shashi Kant

    2013-08-01

    Full Text Available Saturated free fatty acid (FFA is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK pathway that activates cJun NH2-terminal kinase (JNK. Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to the metabolic effects of MLK deficiency. These data confirm that the MLK pathway plays a critical role in the metabolic response to obesity.

  4. SirT1 regulates energy metabolism and response to caloric restriction in mice.

    Gino Boily

    Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

  5. Radiographic and metabolic response rates following image-guided stereotactic radiotherapy for lung tumors

    Mohammed, Nasiruddin; Grills, Inga S.; Wong, Ching-Yee Oliver; Galerani, Ana Paula; Chao, Kenneth; Welsh, Robert; Chmielewski, Gary; Yan Di; Kestin, Larry L.

    2011-01-01

    Purpose: To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors. Materials and methods: Thirty-nine tumors were treated prospectively with SBRT (dose = 48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0 = 67%; T2N0 = 25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses. Results: At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks. Conclusions: SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.

  6. Evaluation of C-Reactive Protein and Fibrinogen in Patients with Chronic and Aggressive Periodontitis: A Clinico-Biochemical Study.

    Chandy, Swaroop; Joseph, Kiran; Sankaranarayanan, Anila; Issac, Annie; Babu, George; Wilson, Bobby; Joseph, Jumol

    2017-03-01

    Periodontal disease is characterised by chronic infection and inflammation in periodontal tissues leading to destruction of alveolar bone with subsequent tooth loss. Periodontal infections are the result of an interaction between tooth associated microbial biofilms and the host defences. Periodontal pathogens can affect local and systemic immune and inflammatory responses. The aim of the present study was to evaluate serum C-Reactive Protein (CRP), plasma fibrinogen and peripheral blood levels in healthy subjects, chronic and aggressive periodontitis patients. A total of 55 subjects, 27 males and 28 females were selected for the study. Blood samples were taken from healthy controls (n=20) and patients with chronic periodontitis (n=20) and aggressive periodontitis (n=15). The periodontal status of each patient was assessed by recording Oral Hygiene Index-Simplified (OHI-S), Bleeding Index (BI), Probing Pocket Depth (PPD) and Clinical Attachment Level (CAL). The levels of serum CRP were measured using high sensitivity Enzyme Linked Immunosorbent Assay (ELISA) and levels of plasma fibrinogen were measured using Quantitative Immunoturbidimetric assay. Data description was done in the form of mean and standard deviation and analysis of data was done using one way ANOVA (Analysis of Variance) and Students t-test to test the statistical significance between groups. The levels of serum CRP and plasma fibrinogen was increased in patients with chronic and aggressive periodontitis when compared to healthy controls (pperiodontitis and cardiovascular diseases.

  7. Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

    Michael J. Haley

    2017-10-01

    Full Text Available Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids. Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

  8. Localization of thrombi using the Ga-67-DFO-DAS fibrinogen

    Takahashi, Eriko; Ohta, Yoshiko; Kawasaki, Sachiko; Maki, Masako; Hiroe, Michiaki; Kusakabe, Kiyoko; Kohno, Atsushi; Shigeta, Akiko

    1985-01-01

    This report shows demonstrable thrombus imaging with Ga-67-DFO-DAS fibrinogen in a patient with Marfan's syndrome. Significant Ga-67-DFO-DAS fibrinogen deposition was noted in the leakage surrounding replased graft of ascending aorta and lesion of pulmonary parenchyma which was suspicious of pulmonary infarction. This results promises that Ga-67-DFO-DAS fibrinogen is a useful tool for evaluation of the clotting under various forms of therapy. (author)

  9. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy

    Davenport, Ross; Brohi, Karim

    2013-01-01

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen con...

  10. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy.

    Davenport, Ross; Brohi, Karim

    2013-09-24

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen concentrate or cryoprecipitate should be considered a clinical priority in major trauma hemorrhage.

  11. Changes in fibrinogen availability and utilization in an animal model of traumatic coagulopathy

    Hagemo, Jostein S; Jørgensen, Jørgen; Ostrowski, Sisse R

    2013-01-01

    Impaired haemostasis following shock and tissue trauma is frequently detected in the trauma setting. These changes occur early, and are associated with increased mortality. The mechanism behind trauma-induced coagulopathy (TIC) is not clear. Several studies highlight the crucial role of fibrinogen...... in posttraumatic haemorrhage. This study explores the coagulation changes in a swine model of early TIC, with emphasis on fibrinogen levels and utilization of fibrinogen....

  12. Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies

    Erika Meroni

    2018-02-01

    Full Text Available The ketogenic diet (KD is a high-fat, low-carbohydrate diet based on the induction of the synthesis of ketone bodies (KB. Despite its widespread use, the systemic impact of KD is not completely understood. The purpose of this study was to evaluate the effects of physiological levels of KB on HMEC-1 endothelial cells. To this aim, DNA oxidative damage and the activation of Nrf2, a known transcriptional factor involved in cell responses to oxidative stress, were assessed. The exposure of cells to KB exerted a moderate genotoxic effect, measured by a significant increase in DNA oxidative damage. However, cells pre-treated with KB for 48 h and subjected to a secondary oxidative insult (H2O2, significantly decreased DNA damage compared to control oxidized cells. This protection occurred by the activation of Nrf2 pathway. In KB-treated cells, we found increased levels of Nrf2 in nuclear extracts and higher gene expression of HO-1, a target gene of Nrf2, compared to control cells. These results suggest that KB, by inducing moderate oxidative stress, activate the transcription factor Nrf2, which induces the transcription of target genes involved in the cellular antioxidant defense system.

  13. RNA metabolism in Xylella fastidiosa during cold adaptation and survival responses

    Fastidious plant pathogen Xylella fastidiosa has a reduced ability to adapt to cold temperatures, limiting persistence in perennial hosts, such as grapevine, growing in colder regions. RNA metabolism is an essential part of bacterial response to low temperature, including inducible expression of RNA...

  14. The effect of environmental temperature on immune response and metabolism of the young chicken

    Henken, A.M.

    1982-01-01

    The effect of environmental temperature on immune response and metabolism was studied in young chickens. Immunization was performed by injecting intramuscularly 0.5 ml packed SRBC (sheep red blood cells) in both thighs of 32 days old pullets ( WarrenSSL ). The

  15. Chromium supplementation enhances the metabolic response of steers to lipopolysaccharide (LPS) challenge

    The effect of chromium (Cr; KemTRACE®brandChromiumProprionate 0.04%, Kemin Industries) supplementation on the metabolic response to LPS challenge was examined. Steers (n=20; 235±4 kg body weight (BW)) received a premix that added 0 (Con) or 0.2 mg/kg Cr to the total diet (DM (dry matter) basis) for ...

  16. The structure of wheat bread influences the postprandial metabolic response in healthy men

    Eelderink, Coby; Noort, Martijn W. J.; Sozer, Nesli; Koehorst, Martijn; Holst, Jens J.; Deacon, Carolyn F.; Rehfeld, Jens F.; Poutanen, Kaisa; Vonk, Roel J.; Oudhuis, Lizette; Priebe, Marion G.

    2015-01-01

    Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with

  17. Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects

    Kempen, K.P.G.; Saris, W.H.M.; Senden, J.M.G.; Menheere, P.P.C.A.; Blaak, E.E.; van Baak, M.A.

    1994-01-01

    Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects. Kempen KP, Saris WH, Senden JM, Menheere PP, Blaak EE, van Baak MA. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. This study was intended to investigate the

  18. Liquid scintillation vial for radiometric assay of lymphocyte carbohydrate metabolism in response to mitogens

    Tran, N.; Wagner, H.N. Jr.

    1978-01-01

    We have demonstrated that mitogens--i.e., PHA and Con.A--stimulate lymphocyte carbohydrate metabolism using a liquid-scintillation vial with conventional liquid-scintillation detectors. The results showed that this enclosed system can be useful for development of rapid in vitro tests of lymphocytes immune responsiveness, as well as for radiometric detection of bacterial growth in various gaseous atmospheres

  19. Origin of endotoxemia influences the metabolic response to endotoxin in dogs

    Moeniralam, H. S.; Bemelman, W. A.; Romijn, J. A.; Endert, E.; Ackermans, M. T.; van Lanschot, J. J.; Hermsen, R. C.; Sauerwein, H. P.

    1997-01-01

    Different routes of endotoxin administration have been used to mimic inflammatory and metabolic responses observed during sepsis. Because the origin of endotoxemia may affect the reactions to endotoxin, we compared the induction of tumor necrosis factor (TNF), interleukin-6 (IL-6), hormones, and

  20. Positron computed tomography studies of cerebral metabolic responses to complex motor tasks

    Phelps, M.E.; Mazziotta, J.C.

    1984-01-01

    Human motor system organization was explored in 8 right-handed male subjects using /sup 18/F-fluorodeoxyglucose and positron computed tomography to measure cerebral glucose metabolism. Five subjects had triple studies (eyes closed) including: control (hold pen in right hand without moving), normal size writing (subject repeatedly writes name) and large (10-15 X normal) name writing. In these studies normal and large size writing had a similar distribution of metabolic responses when compared to control studies. Activations (percent change from control) were in the range of 12-20% and occurred in the striatum bilaterally > contralateral Rolandic cortex > contralateral thalamus. No significant activations were observed in the ipsilateral thalamus, Rolandic cortex or cerebellum (supplementary motor cortex was not examined). The magnitude of the metabolic response in the striatum was greater with the large versus normal sized writing. This differential response may be due to an increased number and topographic distribution of neurons responding with the same average activity between tasks or an increase in the functional activity of the same neuronal population between the two tasks (present spatial resolution inadequate to differentiate). When subjects (N=3) performed novel sequential finger movements, the maximal metabolic response was in the contralateral Rolandic cortex > striatum. Such studies provide a means of exploring human motor system organization, motor learning and provide a basis for examining patients with motor system disorders

  1. Kinetics of Iodine 131 labelled fibrinogen in cancerous patients. Pharmacological study

    Boneu-Valmalette, Andree; Bugat, Roland; David, J.-F.; Combes, P.-F.

    1977-01-01

    The results obtained in a previous study using 131 I fibrinogen in cancerous patients suggested a local intravascular clotting process. In order to elucidate the mechanism of fibrinogen kinetic abnormalities different drugs including heparin, prednisone, ticlopidin, aspirin and indomethacin were administred in 68 patients and their effects evaluated by change in the 131 I fibrinogen disappearance rate. The results suggest that these drugs may counteract with the early stages of coagulation (kinin-forming system, factor XII) and that abnormal 131 I fibrinogen kinetic in cancer would be a non specific phenomenon [fr

  2. Larval starvation improves metabolic response to adult starvation in honey bees (Apis mellifera L.).

    Wang, Ying; Campbell, Jacob B; Kaftanoglu, Osman; Page, Robert E; Amdam, Gro V; Harrison, Jon F

    2016-04-01

    Environmental changes during development have long-term effects on adult phenotypes in diverse organisms. Some of the effects play important roles in helping organisms adapt to different environments, such as insect polymorphism. Others, especially those resulting from an adverse developmental environment, have a negative effect on adult health and fitness. However, recent studies have shown that those phenotypes influenced by early environmental adversity have adaptive value under certain (anticipatory) conditions that are similar to the developmental environment, though evidence is mostly from morphological and behavioral observations and it is still rare at physiological and molecular levels. In the companion study, we applied a short-term starvation treatment to fifth instar honey bee larvae and measured changes in adult morphology, starvation resistance, hormonal and metabolic physiology and gene expression. Our results suggest that honey bees can adaptively respond to the predicted nutritional stress. In the present study, we further hypothesized that developmental starvation specifically improves the metabolic response of adult bees to starvation instead of globally affecting metabolism under well-fed conditions. Here, we produced adult honey bees that had experienced a short-term larval starvation, then we starved them for 12 h and monitored metabolic rate, blood sugar concentrations and metabolic reserves. We found that the bees that experienced larval starvation were able to shift to other fuels faster and better maintain stable blood sugar levels during starvation. However, developmental nutritional stress did not change metabolic rates or blood sugar levels in adult bees under normal conditions. Overall, our study provides further evidence that early larval starvation specifically improves the metabolic responses to adult starvation in honey bees. © 2016. Published by The Company of Biologists Ltd.

  3. Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen.

    Thompson, Aaron M S; Zanobetti, Antonella; Silverman, Frances; Schwartz, Joel; Coull, Brent; Urch, Bruce; Speck, Mary; Brook, Jeffrey R; Manno, Michael; Gold, Diane R

    2010-01-01

    Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardio-vascular disease. We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.080.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.060.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response.

  4. Clotting of mammalian fibrinogens by papain: a re-examination.

    Doolittle, Russell F

    2014-10-28

    Papain has long been known to cause the gelation of mammalian fibrinogens. It has also been reported that papain-fibrin is insoluble in dispersing solvents like strong urea or sodium bromide solutions, similar to what is observed with thrombin-generated clots in the presence of factor XIIIa and calcium. In those old studies, both the gelation and subsequent clot stabilization were attributed to papain, although the possibility that the second step might be due to contaminating factor XIII in fibrinogen preparations was considered. I have revisited this problem in light of knowledge acquired over the past half-century about thiol proteases like papain, which mostly cleave peptide bonds, and transglutaminases like factor XIIIa that catalyze the formation of ε-lysyl-γ-glutamyl cross-links. Recombinant fibrinogen, inherently free of factor XIII and other plasma proteins, formed a stable gel when treated with papain alone. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the intermolecular cross-linking in papain-fibrin leads to γ-chain dimers, trimers, and tetramers, just as is the case with thrombin-factor XIIIa-stabilized fibrin. Mass spectrometry of bands excised from gels showed that the cross-linked material is quite different from what occurs with factor XIIIa, however. With papain, the cross-linking occurs between γ chains in neighboring protofibrils becoming covalently linked in a "head-to-tail" fashion by a transpeptidation reaction involving the α-amino group of γ-Tyr1 and a papain cleavage site at γ-Gly403 near the carboxy terminus, rather than by the (reciprocal) "tail-to-tail" manner that occurs with factor XIIIa and that depends on cross-links between γ-Lys406 and γ-Gln398.

  5. The metabolic cost of mounting an immune response in male brown anoles (Anolis sagrei).

    Cox, Christian L; Peaden, Robert T; Cox, Robert M

    2015-09-09

    The tradeoff between reproduction and survival is central to life-history theory and is thought to reflect underlying energetic tradeoffs between reproduction and self-maintenance. Immune responses to parasites and pathogens are important components of self-maintenance in many species, but whether these defenses impose significant energetic costs has only been tested in a handful of organisms. We tested for a metabolic cost of mounting an immune response in the male brown anole (Anolis sagrei), a lizard in which we have previously shown that reproduction causes a marked reduction in immune response to the novel antigen phytohaemagglutinin (PHA). We treated captive male anoles with a subcutaneous injection of either PHA, which induces an immune response that manifests as localized swelling, or saline vehicle as a control. Prior to injection and at 24, 48, and 72 hr post-injection, we measured swelling at the site of injection and whole-animal resting metabolic rate (RMR) using stop-flow respirometry. Although we detected a robust swelling response to PHA at 24, 48, and 72 hr post-injection, mean RMR did not differ between treatments at any of these time points. However, within the PHA treatment group, RMR increased with the extent of swelling, suggesting a variable metabolic cost that scales with the magnitude of the induced immune response. Although individual anoles varied considerably in the extent to which they responded to PHA challenge, our results suggest that an immune response can impose a substantial metabolic cost (potentially as much as 63% above baseline RMR) for individuals that do respond maximally. J. Exp. Zool. 9999A:XX-XX, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-01-01

    Abstract Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle

  7. Study of the fibrinogen - fibrin transformation kinetics and modifications caused to this reaction by irradiation (X rays) of the fibrinogen solution

    Hollard, D.; Suscillon, M.; Marcille, G.; Rambaud, F.; Baloyan, M.

    1966-01-01

    The authors present a spectrophotometric method for studying the transformation fibrinogen - fibrin. This method has the advantage of drawing immediately in graph form the three, phases of this transformation: proteolysis or monomerization; polymerisation; clot stabilization. It is a simple, faithful and easily reproductive technic. Owing to this method, they studied modifications of this transformation due to irradiation of fibrinogen solution. Low doses (90 000 R/mn) prevent transverse polymerisation. To upper doses (180 000 R and more), the action of thrombin on fibrinogen does not give an organised clot but a lacteous and fragile gel. There is not here a coagulation in the physiological understanding. (author) [fr

  8. Thin films growth parameters in MAPLE; application to fibrinogen

    Jelinek, M; Cristescu, R; Kocourek, T; Vorlicek, V; Remsa, J; Stamatin, L; Mihaiescu, D; Stamatin, I; Mihailescu, I N; Chrisey, D B

    2007-01-01

    Increasingly requirements on the thin film quality of functionalized materials are efficiently met by a novel laser processing technique - Matrix Assisted Pulsed Laser Evaporation (MAPLE). Examples of deposition conditions and main features characteristic to film growth rate of MAPLE-fabricated organic materials are summarized. MAPLE experimental results are compared with ones corresponding to the classical Pulsed Laser Deposition (PLD). In particular, the results of investigation of MAPLE-deposited fibrinogen blood protein thin films using a KrF* excimer laser and characterized by FTIR and Raman spectrometry are reported

  9. Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase.

    Choi, Hyun B; Gordon, Grant R J; Zhou, Ning; Tai, Chao; Rungta, Ravi L; Martinez, Jennifer; Milner, Teresa A; Ryu, Jae K; McLarnon, James G; Tresguerres, Martin; Levin, Lonny R; Buck, Jochen; MacVicar, Brian A

    2012-09-20

    Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO₃⁻) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO₃⁻ entry via the electrogenic NaHCO₃ cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K⁺](ext) and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Muscular and metabolic responses to different Nordic walking techniques, when style matters.

    Pellegrini, Barbara; Boccia, Gennaro; Zoppirolli, Chiara; Rosa, Raffaela; Stella, Federico; Bortolan, Lorenzo; Rainoldi, Alberto; Schena, Federico

    2018-01-01

    Due to poling action and upper body engagement, Nordic walking (NW) has additional health benefits with respect to conventional walking. The aim of this study was to evaluate the differences in muscle activation and metabolic responses between NW, performed with the technique suggested by NW instructors, and with some modifications in the way to move upper limb and poles. Ten NW instructors volunteered to walk on a treadmill at 5.5 km•h-1 in five conditions: walking (W), Nordic walking (NW), NW with a weak poling action (NWweak), with straight-upper limbs moving the shoulders (NWshoulder) and with elbow flexion-extension pattern and shoulder freezed (NWelbow). Poling forces, body segments and poles movement, upper and lower body muscle activation, as well as metabolic parameters were measured.All modified NW techniques elicited lower muscular activation and metabolic responses with respect to the suggested NW technique (P walking instructors, sport technicians and practitioners should be aware that any deviation from the technique usually suggested might lead to lower benefits. However it is worth to note that any walking technique with poles elicits higher metabolic responses and muscular activation than walking.

  11. Changes in energy metabolism in response to 48 h of overfeeding and fasting in Caucasians and Pima Indians

    Weyer, C; Vozarova, B; Ravussin, E

    2001-01-01

    Differences in the metabolic response to overfeeding and starvation may confer susceptibility or resistance to obesity in humans. To further examine this hypothesis, we assessed the changes in 24 h energy metabolism in response to short-term overfeeding and fasting in Caucasians (C) and Pima...... Indians (I), a population with a very high propensity for obesity....

  12. Investigating the Cellular and Metabolic Responses of World-Class Canoeists Training: A Sportomics Approach

    Wagner Santos Coelho

    2016-11-01

    Full Text Available (1 Background: We have been using the Sportomics approach to evaluate biochemical and hematological changes in response to exercise. The aim of this study was to evaluate the metabolic and hematologic responses of world-class canoeists during a training session; (2 Methods: Blood samples were taken at different points and analyzed for their hematological properties, activities of selected enzymes, hormones, and metabolites; (3 Results: Muscle stress biomarkers were elevated in response to exercise which correlated with modifications in the profile of white blood cells, where a leukocyte rise was observed after the canoe session. These results were accompanied by an increase in other exercise intensity parameters such as lactatemia and ammonemia. Adrenocorticotropic hormone and cortisol increased during the exercise sessions. The acute rise in both erythrocytes and white blood profile were probably due to muscle cell damage, rather than hepatocyte integrity impairment; (4 Conclusion: The cellular and metabolic responses found here, together with effective nutrition support, are crucial to understanding the effects of exercise in order to assist in the creation of new training and recovery planning. Also we show that Sportomics is a primal tool for training management and performance improvement, as well as to the understanding of metabolic response to exercise.

  13. Metabolic response to optic centers to visual stimuli in the albino rat: anatomical and physiological considerations

    Toga, A.W.; Collins, R.C.

    1981-01-01

    The functional organization of the visual system was studied in the albino rat. Metabolic differences were measured using the 14 C-2-deoxyglucose (DG) autoradiographic technique during visual stimulation of one entire retina in unrestrained animals. All optic centers responded to changes in light intensity but to different degrees. The greatest change occurred in the superior colliculus, less in the lateral geniculate, and considerably less in second-order sites such as layer IV of visual cortex. These optic centers responded in particular to on/off stimuli, but showed no incremental change during pattern reversal or movement of orientation stimuli. Both the superior colliculus and lateral geniculate increased their metabolic rate as the frequency of stimulation increased, but the magnitude was twice as great in the colliculus. The histological pattern of metabolic change in the visual system was not homogenous. In the superior colliculus glucose utilization increased only in stratum griseum superficiale and was greatest in visuotopic regions representing the peripheral portions of the visual field. Similarly, in the lateral geniculate, only the dorsal nucleus showed an increased response to greater stimulus frequencies. Second-order regions of the visual system showed changes in metabolism in response to visual stimulation, but no incremental response specific for type or frequency of stimuli. To label proteins of axoplasmic transport to study the terminal fields of retinal projections 14 C-amino acids were used. This was done to study how the differences in the magnitude of the metabolic response among optic centers were related to the relative quantity of retinofugal projections to these centers

  14. Influence of low- and high-dose radioiodine therapy on oxidative modification of fibrinogen

    Schweeger-Exeli, I.J.

    2001-10-01

    Fibrinogen plays a central role in the course of thrombosis and hemostasis. It is soluble in blood and tissue extracts and transformed into the insoluble fibrin network structure in the presence of thrombin. Fibrinogen in circulating blood consists of a population of slightly different molecules with a half-life of 3.5-4.5 days. Various environmental conditions may cause different types of modifications of the molecule leading to a different functional behavior. Introduction of carbonyl groups in amino acid side chains is known as a marker for protein oxidation. Radioiodine therapy, applied in patients suffering from hyperthyroidism or differentiated thyroid carcinoma, may cause an oxidative modification of fibrinogen by formation of free radicals in blood exposed to the radioactive agent 131I. The topic of my thesis was i. to develop a simple and not time consuming method for isolation of fibrinogen from small volumes of human plasma (∼ 6ml), ii. to assess, whether radioiodine therapy causes detectable introduction of carbonyl groups into the fibrinogen molecule, and iii. to analyze an association between thyroid hormone function, fibrinogen levels and protein oxidation by means of carbonyl content. Purification of fibrinogen from human plasma was possible by three different methods (ammonium sulphate/ethanol; glycine/ethanol; glycine). Plasma levels of fibrinogen (Clauss method) and protein carbonyl group content (2,4-DNPH - assay) were determined before and after radioiodine therapy. The results demonstrate a significant increase (p = 0.05) in carbonyl content of human fibrinogen in cancer patients treated with 131I. However, in patients with diagnosed hyperthyroidism values were not significantly altered. In carcinoma patients, baseline fT4 levels and the relative increase in carbonyl content of fibrinogen after radioiodine therapy were correlated (r = 0.83; p 0.005), whereas no such correlation was found in patients with hyperthyroidism. Plasma fibrinogen

  15. Role of Glucocorticoids in the Response to Unloading of Muscle Protein and Amino Acid Metabolism

    Tischler, M. E.; Jaspers, S. R.

    1985-01-01

    Intact control (weight bearing) and suspended rats gained weight at a similar rate during a 6 day period. Adrenaectomized (adx) weight bearing rats gained less weight during this period while adrenalectomized suspended rats showed no significant weight gain. Cortisol treatment of both of these groups of animals caused a loss of body weight. Results from these studies show several important findings: (1) Metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating gluccorticoids; (2) Metabolic changes in the soleus due to higher steroid levels are probably potentiated by greater numbers of receptors; and (3) Not all metabolic responses in the unloaded soleus muscle are due to direct action of elevated glucocorticoids or increased sensitivity to these hormones.

  16. Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

    Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

    2003-07-01

    Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

  17. The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism

    Katsumi Iizuka

    2017-02-01

    Full Text Available Many articles have discussed the relationship between fructose consumption and the incidence of obesity and related diseases. Fructose is absorbed in the intestine and metabolized in the liver to glucose, lactate, glycogen, and, to a lesser extent, lipids. Unabsorbed fructose causes bacterial fermentation, resulting in irritable bowl syndrome. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important for the treatment of metabolic syndrome and fructose malabsorption. Carbohydrate response element binding protein (ChREBP is a glucose-activated transcription factor that controls approximately 50% of de novo lipogenesis in the liver. ChREBP target genes are involved in glycolysis (Glut2, liver pyruvate kinase, fructolysis (Glut5, ketohexokinase, and lipogenesis (acetyl CoA carboxylase, fatty acid synthase. ChREBP gene deletion protects against high sucrose diet-induced and leptin-deficient obesity, because Chrebp−/− mice cannot consume fructose or sucrose. Moreover, ChREBP contributes to some of the physiological effects of fructose on sweet taste preference and glucose production through regulation of ChREBP target genes, such as fibroblast growth factor-21 and glucose-6-phosphatase catalytic subunits. Thus, ChREBP might play roles in fructose metabolism. Restriction of excess fructose intake will be beneficial for preventing not only metabolic syndrome but also irritable bowl syndrome.

  18. Release of peptides from Fibrinogen in vitro and in vivo

    Weibel, S.

    1986-01-01

    The dissertation deals experimentally with the following problem fields: The attempt was made to obtain extremely pure, native peptides from fibrinogen with micropreparation with the help of high-pressure liquid chromatography (HPLC); a HPLC-pure antigen which could be labelled (DAT-FPA) was also to be produced and a HPLC-purified, labelled antigen (J 125 DAT-FPA) for the radioimmunoassay was to be prepared. By applying HPLC-purified FPA-material to immunise rabbits, a highly specific antibody against FPA was obtained, and the radioimmunoassay was decisively improved. Furthermore, a method with a high recovery rate specific for the A-peptides could be found. A procedure was developed which is able to separate the modifications from the plasma from one another and to prove them specifically in ng-quantities. This is the first time that the sensitive method of high-pressure liquid chromatography is used to observe the effects of the snake venom enzymes on fibrinogen over a period of 20 hrs. The kinetics of intravenously administered J 123 DAT-FPA and, in comparison, J 123 FPB β 15-42 in vivo in rabbits with the help of a scintiscanning method, was investigated and the distribution in the organism and the ways of elimination were determined. (orig./MG) [de

  19. Dynamic Responses of Phosphorus Metabolism to Acute and Chronic Dietary Phosphorus-Limitation in Daphnia

    Nicole D. Wagner

    2017-06-01

    Full Text Available Food quality is highly dynamic within lake ecosystems and varies spatially and temporally over the growing season. Consumers may need to continuously adjust their metabolism in response to this variation in dietary nutrient content. However, the rates of metabolic responses to changes in food nutrient content has received little direct study. Here, we examine responses in two metabolic phosphorus (P pools, ribonucleic acids (RNA and adenosine triphosphate (ATP, along with body mass and body P content in Daphnia magna exposed to chronic and acute dietary P-limitation. First, we examined food quality effects on animals consuming different food carbon (C:P quality over a 14 day period. Then, we raised daphnids on one food quality for 4 days, switched them to contrasting dietary treatments, and measured changes in their metabolic responses at shorter time-scales (over 48 h. Animal P, RNA, and ATP content all changed through ontogeny with adults containing relatively less of these pools with increasing body mass. Irrespective of age, Daphnia consuming high C:P diets had lower body %P, %RNA, %ATP, and mass compared to animals eating low C:P diets. Diet switching experiments revealed diet dependent changes in body %P, %RNA, %ATP, and animal mass within 48 h. We found that Daphnia switched from low to high C:P diets had some metabolic buffering capacity with decreases in body %P occurring after 24 h but mass remaining similar to initial diet conditions for 36 h after the diet switch. Switching Daphnia from low to high C:P diets caused a decrease in the RNA:P ratio after 48 h. Daphnia switched from high to low C:P diets increased their body P, RNA, and ATP content within 8–24 h. This switch from high to low C:P diets also led to increased RNA:P ratios in animal bodies. Overall, our study revealed that consumer P metabolism reflects both current and past diet due to more dynamic and rapid changes in P biochemistry than total body mass. This metabolic

  20. Ruminant Nutrition Symposium: ruminant production and metabolic responses to heat stress.

    Baumgard, L H; Rhoads, R P

    2012-06-01

    Heat stress compromises efficient animal production by marginalizing nutrition, management, and genetic selection efforts to maximize performance endpoints. Modifying farm infrastructure has yielded modest success in mitigating heat stress-related losses, yet poor production during the summer remains arguably the costliest issue facing livestock producers. Reduced output (e.g., milk yield and muscle growth) during heat stress was traditionally thought to result from decreased nutrient intake (i.e., a classic biological response shared by all animals during environmental-induced hyperthermia). Our recent observations have begun to challenge this belief and indicate heat-stressed animals employ novel homeorhetic strategies to direct metabolic and fuel selection priorities independently of nutrient intake or energy balance. Alterations in systemic physiology support a shift in carbohydrate metabolism, evident by increased basal and stimulated circulating insulin concentrations. Perhaps most intriguing given the energetic shortfall of the heat-stressed animal is the apparent lack of basal adipose tissue mobilization coupled with a reduced responsiveness to lipolytic stimuli. Thus, the heat stress response markedly alters postabsorptive carbohydrate, lipid, and protein metabolism independently of reduced feed intake through coordinated changes in fuel supply and utilization by multiple tissues. Interestingly, the systemic, cellular, and molecular changes appear conserved amongst different species and physiological states. Ultimately, these changes result in the reprioritization of fuel selection during heat stress, which appears to be primarily responsible for reduced ruminant animal productivity during the warm summer months.

  1. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

    Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

    2016-10-01

    Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

  2. Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

    Bloor, Ian D; Sébert, Sylvain P; Saroha, Vivek; Gardner, David S; Keisler, Duane H; Budge, Helen; Symonds, Michael E; Mahajan, Ravi P

    2013-10-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

  3. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    Baud, Maxime O.

    2016-05-03

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.

  4. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction.

    Volek, Jeff S; Feinman, Richard D

    2005-11-16

    surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

  5. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

    Feinman Richard D

    2005-11-01

    conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

  6. The effect of temperature and body weight on the routine metabolic rate and postprandial metabolic response in mulloway, Argyrosomus japonicus.

    Pirozzi, Igor; Booth, Mark A

    2009-09-01

    Specific dynamic action (SDA) is the energy expended on the physiological processes associated with meal digestion and is strongly influenced by the characteristics of the meal and the body weight (BW) and temperature of the organism. This study assessed the effects of temperature and body weight on the routine metabolic rate (RMR) and postprandial metabolic response in mulloway, Argyrosomus japonicus. RMR and SDA were established at 3 temperatures (14, 20 and 26 degrees C). 5 size classes of mulloway ranging from 60 g to 1.14 kg were used to establish RMR with 3 of the 5 size classes (60, 120 and 240 g) used to establish SDA. The effect of body size on the mass-specific RMR (mg O(2) kg(-1) h(-1)) varied significantly depending on the temperature; there was a greater relative increase in the mass-specific RMR for smaller mulloway with increasing temperature. No statistical differences were found between the mass exponent (b) values at each temperature when tested against H(0): b=0.8. The gross RMR of mulloway (mg O(2) fish(-1) h(-1)) can be described as function of temperature (T; 14-26 degrees C) as: (0.0195T-0.0454)BW(g)(0.8) and the mass-specific RMR (mg O(2) kg(-1) h(-1)) can be described as: (21.042T-74.867)BW(g)(-0.2). Both SDA duration and time to peak SDA were influenced by temperature and body weight; SDA duration occurred within 41-89 h and peak time occurred within 17-38 h of feeding. The effect of body size on peak metabolic rate varied significantly depending on temperature, generally increasing with temperature and decreasing with increasing body size. Peak gross oxygen consumption (MO(2): mg O(2) fish(-1) h(-1)) scaled allometrically with BW. Temperature, but not body size, significantly affected SDA scope, although the difference was numerically small. There was a trend for MO(2) above RMR over the SDA period to increase with temperature; however, this was not statistically significant. The average proportion of energy expended over the SDA period

  7. Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine

    Roseboom, T. J.; van der Meulen, J. H.; Ravelli, A. C.; Osmond, C.; Barker, D. J.; Bleker, O. P.

    2000-01-01

    To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by

  8. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease

    Dahl, Morten; Tybjaerg-Hansen, A; Vestbo, J

    2001-01-01

    We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD...

  9. The binding of 125I-fibrinogen to blood platelets in patients with chronic uraemia

    Komarnicki, M.; Zozulinska, M.; Zawilska, K.

    1987-01-01

    The binding of 125 I-fibrinogen to blood platelets was assessed in 41 patients with chronic uremia. The study was performed in three groups of subjects: treated conservatively, with hemodialysis and with peritoneal dialysis. Platelets from uremic patients were shown to be more susceptible to fibrinogen binding than platelets from healthy subjects. (author)

  10. Circulating fibrinogen but not D-dimer level is associated with vital exhaustion in school teachers.

    Kudielka, Brigitte M; Bellingrath, Silja; von Känel, Roland

    2008-07-01

    Meta-analyses have established elevated fibrinogen and D-dimer levels in the circulation as biological risk factors for the development and progression of coronary artery disease (CAD). Here, we investigated whether vital exhaustion (VE), a known psychosocial risk factor for CAD, is associated with fibrinogen and D-dimer levels in a sample of apparently healthy school teachers. The teaching profession has been proposed as a potentially high stressful occupation due to enhanced psychosocial stress at the workplace. Plasma fibrinogen and D-dimer levels were measured in 150 middle-aged male and female teachers derived from the first year of the Trier-Teacher-Stress-Study. Log-transformed levels were analyzed using linear regression. Results yielded a significant association between VE and fibrinogen (p = 0.02) but not D-dimer controlling for relevant covariates. Further investigation of possible interaction effects resulted in a significant association between fibrinogen and the interaction term "VE x gender" (p = 0.05). In a secondary analysis, we reran linear regression models for males and females separately. Gender-specific results revealed that the association between fibrinogen and VE remained significant in males but not females. In sum, the present data support the notion that fibrinogen levels are positively related to VE. Elevated fibrinogen might be one biological pathway by which chronic work stress may impact on teachers' cardiovascular health in the long run.

  11. A study on human serum albumin influence on glycation of fibrinogen

    Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr

    2013-01-01

    Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [ 13 C 6 ] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein

  12. Positive imaging of venous thrombi and thromboemboli with Ga-67 DFO-DAS-fibrinogen

    Yamamoto, Kazutaka; Senda, Michio; Fujita, Toru; Yonekura, Yoshiharu; Kumada, Kaoru; Yokoyama, Akira; Torizuka, Kanji

    1988-05-01

    A newly developed thrombus imaging agent, /sup 67/Ga-DFO-DAS-fibrinogen (/sup 67/Ga-fibrinogen), was used for 22 studies in 20 cases of suspected deep venous thrombosis. Increased accumulation of /sup 67/Ga-fibrinogen in venous thrombi was depicted at 48 h after injection in 10 of the 15 cases (10 of 17 studies) who showed abnormal findings in radionuclide venography. A hot spot in the lung emboli was visualized in two cases. Seven of the eight cases having anticoagulant therapy showed increased /sup 67/Ga-fibrinogen uptake, while follow-up /sup 67/Ga-fibrinogen scintigraphy after the administration of heparin and urokinase did not reveal an abnormal hot spot in one case. /sup 67/Ga-fibrinogen can be made available simply by adding /sup 67/Ga solution to a vial containing fibrinogen-DAS-DFO conjugate. In conclusion, /sup 67/Ga-fibrinogen is considered to be a promising agent for detecting active venous thrombi and to assess the effect of anticoagulant therapy.

  13. Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary hyperlipidaemia

    de Maat, M. P.; Knipscheer, H. C.; Kastelein, J. J.; Kluft, C.

    1997-01-01

    An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. One group of agents with this capacity are the fibric acid derivatives,

  14. A study on human serum albumin influence on glycation of fibrinogen

    Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr, E-mail: Piotr.stefanowicz@chem.uni.wroc.pl

    2013-09-13

    Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [{sup 13}C{sub 6}] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein.

  15. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

    Wittmann Christoph

    2008-03-01

    Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

  16. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    Choue Ryowon

    2011-07-01

    Full Text Available Abstract Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collection, anthropometry, blood and urinary analysis, and dietary assessment were conducted. Results They consumed large amounts of protein (4.3 ± 1.2 g/kg BW/day and calories (5,621.7 ± 1,354.7 kcal/day, as well as more than the recommended amounts of vitamins and minerals, including potassium and calcium. Serum creatinine (1.3 ± 0.1 mg/dl and potassium (5.9 ± 0.8 mmol/L, and urinary urea nitrogen (24.7 ± 9.5 mg/dl and creatinine (2.3 ± 0.7 mg/dl were observed to be higher than the normal reference ranges. Urinary calcium (0.3 ± 0.1 mg/dl, and phosphorus (1.3 ± 0.4 mg/dl were on the border of upper limit of the reference range and the urine pH was in normal range. Conclusions Increased urinary excretion of urea nitrogen and creatinine might be due to the high rates of protein metabolism that follow high protein intake and muscle turnover. The obvious evidence of metabolic acidosis in response to high protein diet in the subjects with high potassium intake and intensive resistance exercise were not shown in this study results. However, this study implied that resistance exercise with adequate mineral supplementation, such as potassium and calcium, could reduce or offset the negative effects of protein-generated metabolic changes. This study provides preliminary information of metabolic response to high protein intake in bodybuilders who engaged in high-intensity resistance exercise. Further studies will be needed to determine the effects of the intensity

  17. Deciphering the mechanisms involved in Portulaca oleracea (C4) response to drought: metabolic changes including crassulacean acid-like metabolism induction and reversal upon re-watering.

    D'Andrea, Rodrigo Matías; Andreo, Carlos Santiago; Lara, María Valeria

    2014-11-01

    Portulaca oleracea is a C(4) plant; however, under drought it can change its carbon fixation metabolism into a crassulacean acid metabolism (CAM)-like one. While the C(3) -CAM shift is well known, the C(4) -CAM transition has only been described in Portulaca. Here, a CAM-like metabolism was induced in P. oleracea by drought and then reversed by re-watering. Physiological and biochemical approaches were undertaken to evaluate the drought and recovery responses. In CAM-like plants, chlorophyll fluorescence parameters were transitory affected and non-radiative energy dissipation mechanisms were induced. Induction of flavonoids, betalains and antioxidant machinery may be involved in photosynthetic machinery protection. Metabolic analysis highlights a clear metabolic shift, when a CAM-like metabolism is induced and then reversed. Increases in nitrogenous compounds like free amino acids and urea, and of pinitol could contribute to withstand drought. Reciprocal variations in arginase and urease in drought-stressed and in re-watered plants suggest urea synthesis is strictly regulated. Recovery of C(4) metabolism was accounted by CO(2) assimilation pattern and malate levels. Increases in glycerol and in polyamines would be of importance of re-watered plants. Collectively, in P. oleracea multiple strategies, from induction of several metabolites to the transitory development of a CAM-like metabolism, participate to enhance its adaptation to drought. © 2014 Scandinavian Plant Physiology Society.

  18. The changes in the fibrinogen concentration and coagulation pathways in winter and summer in cattle

    ameneh khoshvaghti

    2013-08-01

    Full Text Available Fibrinogen is an important coagulation factor and a positive acute phase protein and its levels increases in cases of inflammation infection and stress. The present research was done to determine whether the fibrinogen concentration, prothrombin time (PT and activated partial thromboplastin time (APTT can be affected by seasonal changes. In this study, the blood of ten apparently healthy cows from around Yasouj city were taken under aseptic conditions and, then the plasma was separated. The fibrinogen concentration, was assayed by sedimentation refractometry method, PT and APTT were measurement by coagolometric method. The statistical analysis indicated that there was significant difference between the mean concentration of fibrinogen in summer and winter (P0.05. It is concluded that seasonal changes can affect the fibrinogen concentration but does no affect PT and APTT significantly.

  19. Association of fibrinogen with HbA1C in diabetic foot ulcer

    Pase, M. A.; Gatot, D.; Lindarto, D.

    2018-03-01

    Fibrinogen is one of the inflammatory markers of vascular changes and endothelial dysfunction in diabetic patients. The aim of this study to associate serum fibrinogen levels with HbA1C in diabetic foot ulcer (DFU). This study was cross-sectional and retrospective in DFU patients from January to July 2017 in Haji Adam Malik Central General Hospital. The patients enrolled in the study were T2DM with DFU as a complication. The grading of DFU was evaluated according to the Wagner’s Classification. Serum fibrinogen level, HbA1C and ankle-brachial index (ABI) were carried out directly in the patients. Fibrinogen serum levels were found significantly with HbA1C (P=0.001, r=0.387) and ABI (P=0.008, r=-0.454). Fibrinogen serum levels in DFU patients were positively correlated with HbA1C and significantly higher in patients with poor glycemic control.

  20. Effect of dietary restriction on immune response of laboratory mice divergently selected for basal metabolic rate.

    Książek, Aneta; Konarzewski, Marek

    2012-01-01

    To study whether dietary restriction (DR; 70% of ad lib. feeding)-elicited immunosuppression results from the trade-off between the costs of mounting an immune response and the metabolic costs of maintenance, we subjected mice from two divergent lines selected for high basal metabolic rate (H-BMR) and low BMR (L-BMR) to 4 wk of DR and then challenged them with keyhole limpet hemocyanin (KLH) antigen. Those line types differ genetically with respect to BMR and to the mass of metabolically expensive internal organs, which are larger in H-BMR mice. In mice of both line types, DR resulted in a significant reduction of body mass, an immune response, and the downsizing of spleen, lymph nodes, thymus, heart, and kidneys but not small intestines. DR resulted in a greater reduction of the spleen and lymph nodes in mice of the H-BMR line type, whereas the thymus was more affected in L-BMR line type. In contrast, immunization resulted in an increase of liver mass in DR mice of both line types. A comparison of the results of current and earlier studies on the same mouse line types suggests that metabolic trade-offs involving the costs of an immune response are more apparent when animals are forced to increase energy demands (e.g., by cold exposure) compared to when energy demands are decreased through DR. Our findings also suggest that divelrgent selection on BMR resulted in between-line-type differences in T-cell- and B-cell-mediated types of an immune response. More generally, our results indicate that production of a wide repertoire of antibodies is not correlated with high BMR.

  1. Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

    Xiao, Yang; Kwong, Mandy; Daemen, Anneleen; Belvin, Marcia; Liang, Xiaorong; Hatzivassiliou, Georgia; O'Brien, Thomas

    2016-01-01

    Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334), one that shows intermediate sensitivity (NCI-H441), and one that is insensitive (LC-KJ). Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP) and had lower reactive oxygen species (ROS) levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

  2. Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

    Yang Xiao

    Full Text Available Nicotinamide adenine dinucleotide (NAD is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM to nicotinamide mononucleotide (NMN, the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334, one that shows intermediate sensitivity (NCI-H441, and one that is insensitive (LC-KJ. Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP and had lower reactive oxygen species (ROS levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

  3. Metabolic cost of neuronal information in an empirical stimulus-response model

    Košťál, Lubomír; Lánský, Petr; McDonnell, M.D.

    2013-01-01

    Roč. 107, č. 3 (2013), s. 355-365 ISSN 0340-1200 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP103/11/0282; GA ČR(CZ) GPP103/12/P558 Institutional support: RVO:67985823 Keywords : information capacity * metabolic cost * stimulus-response curve Subject RIV: FH - Neurology Impact factor: 1.933, year: 2013

  4. Exercise electrocardiographic responses and serum cystatin C levels among metabolic syndrome patients without overt diabetes mellitus

    Tanindi A

    2011-02-01

    Full Text Available Asli Tanindi1 Hilal Olgun1 Ayse Tuncel2 Bulent Celik3 Hatice Pasaoglu2 Bulent Boyaci11Department of Cardiology, 2Department of Medical Biochemistry, Faculty of Medicine, 3Department of Statistics, Faculty of Health Sciences, Gazi University, Ankara, TurkeyObjectives: An impaired heart rate response during exercise (chronotropic incompetence and an impaired heart rate recovery (HRR after exercise are predictors of cardiovascular risk and mortality. Cystatin C is a novel marker for cardiovascular disease. We aimed to investigate exercise electrocardiographic responses in patients with metabolic syndrome who were without overt diabetes mellitus, in addition to the association of serum cystatin C levels with the exercise electrocardiographic test results.Method: Forty-three consecutive patients admitted to a cardiology outpatient clinic without angina pectoris were recruited if they met criteria for metabolic syndrome but did not have overt diabetes mellitus. Serum cystatin C levels were measured, and all participants underwent exercise electrocardiographic testing. Patients who were found to have ischemia had a coronary angiography procedure.Results: The mean cystatin C level of patients was higher in metabolic syndrome group than healthy controls (610.1 ± 334.02 vs 337.3 ± 111.01 µg/L; P < 0.001. The percentage of patients with ischemia confirmed by coronary angiography was 13.9% in the metabolic syndrome group. Cystatin C levels in the ischemic patients of the metabolic syndrome group were higher than that in nonischemic patients (957.00 ± 375.6 vs 553.8 ± 295.3 µg /L; P = 0.005. Chronotropic incompetence was observed in 30.2% of the patients with metabolic syndrome compared with 16.7% in the control group (P = 0.186. Chronotropic response indices were 0.8 ± 0.18 versus 0.9 ± 0.10 for the two groups, respectively (P = 0.259. HRR was significantly lower in the metabolic syndrome patients compared with the controls (20.1 ± 8.01 vs 25.2

  5. Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge.

    Flavia Badoud

    Full Text Available To determine if metabolically healthy obese (MHO individuals have a different metabolic response to a standardized diet compared to lean healthy (LH and metabolically unhealthy obese (MUO individuals.Thirty adults (35-70 yrs were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal. Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs and derivatives, and fatty acids (FAs.The postprandial response (i.e., area under the curve, AUC for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05. Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, γ-linolenic acid, arachidonic acid showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA and FAs (e.g., saturated myristic and palmitic acids were found to correlate with glucose and insulin AUC.MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals.

  6. Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis.

    Sun, Xuhong; Berthiller, Julien; Trouillas, Paul; Derex, Laurent; Diallo, Laho; Hanss, Michel

    2015-04-15

    The purpose of this study was to systematically determine the correlations between the post-thrombolytic changes of hemostasis parameters and the occurrence of early intracerebral hemorrhage (ICH). In 72 consecutive patients with cerebral infarcts treated with rt-PA, plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, factor XIII, fibrin(ogen) degradation products (FDPs) and d-Dimers were measured at baseline, 2 and 24h after thrombolysis. Correlations were studied between the hemostasis events and early (less than 24h) hemorrhagic infarcts (HIs) or parenchymatous hematomas (PH). Of 72 patients, 6 patients (8.3%) had early PHs, 11 (15.3%) had early HIs, and 55 (76.4%) had no bleeding. Early HIs were not linked to any hemostasis parameter at any time. Univariate comparison of patients having early PHs with non-bleeding patients showed hemostasis abnormalities at 2h: high FDP (p=0.01), high Log FDP (p=0.01), low fibrinogen (p=0.01), and low Log fibrinogen (p=0.01). Logistic regression adjusted for age, NIHSS and diabetes confirmed these 2hour predictors: Log FDP (OR: 7.50; CI: 1.26 to 44.61, p=0.03), and Log fibrinogen (OR: 19.32; CI: 1.81 to 205.98, p=0.01). The decrease in fibrinogen less than 2g/L multiplies the odds of early PH by a factor 12.82. An early fibrinogen degradation coagulopathy involving an increase of FDP and a massive consumption of circulating fibrinogen is predictive of early parenchymal hematomas, indicating the occurrence of a particularly intense lysis of circulating fibrinogen. These results, if confirmed by future studies, suggest that early assays of fibrinogen and FDP may be useful in predicting the risk of post-thrombolytic intracerebral hematoma. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in obese Zucker rats.

    Overton, J M; Williams, T D; Chambers, J B; Rashotte, M E

    2001-04-01

    The primary purpose of the study was to test the hypothesis that reduced leptin signaling is necessary to elicit the cardiovascular and metabolic responses to fasting. Lean (Fa/?; normal leptin receptor; n = 7) and obese (fa/fa; mutated leptin receptor; n = 8) Zucker rats were instrumented with telemetry transmitters and housed in metabolic chambers at 23 degrees C (12:12-h light-dark cycle) for continuous (24 h) measurement of metabolic and cardiovascular variables. Before fasting, mean arterial pressure (MAP) was higher (MAP: obese = 103 +/- 3; lean = 94 +/- 1 mmHg), whereas oxygen consumption (VO(2): obese = 16.5 +/- 0.3; lean = 18.6 +/- 0.2 ml. min(-1). kg(-0.75)) was lower in obese Zucker rats compared with their lean controls. Two days of fasting had no effect on MAP in either lean or obese Zucker rats, whereas VO(2) (obese = -3.1 +/- 0.3; lean = -2.9 +/- 0.1 ml. min(-1). kg(-0.75)) and heart rate (HR: obese = -56 +/- 4; lean = -42 +/- 4 beats/min) were decreased markedly in both groups. Fasting increased HR variability both in lean (+1.8 +/- 0.4 ms) and obese (+2.6 +/- 0.3 ms) Zucker rats. After a 6-day period of ad libitum refeeding, when all parameters had returned to near baseline levels, the cardiovascular and metabolic responses to 2 days of thermoneutrality (ambient temperature 29 degrees C) were determined. Thermoneutrality reduced VO(2) (obese = -2.4 +/- 0.2; lean = -3.3 +/- 0.2 ml. min(-1). kg(-0.75)), HR (obese = -46 +/- 5; lean = -55 +/- 4 beats/min), and MAP (obese = -13 +/- 6; lean = -10 +/- 1 mmHg) similarly in lean and obese Zucker rats. The results indicate that the cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in Zucker rats and suggest that intact leptin signaling may not be requisite for the metabolic and cardiovascular responses to reduced energy intake.

  8. The structure of wheat bread influences the postprandial metabolic response in healthy men.

    Eelderink, Coby; Noort, Martijn W J; Sozer, Nesli; Koehorst, Martijn; Holst, Jens J; Deacon, Carolyn F; Rehfeld, Jens F; Poutanen, Kaisa; Vonk, Roel J; Oudhuis, Lizette; Priebe, Marion G

    2015-10-01

    Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with a similar composition were created using different processing conditions. The postprandial glucose kinetics and metabolic response to bread with a compact structure (flat bread, FB) was compared to bread with a porous structure (control bread, CB) in a randomized, crossover study with ten healthy male volunteers. Pasta (PA), with a very compact structure, was used as the control. The rate of appearance of exogenous glucose (RaE), endogenous glucose production, and glucose clearance rate (GCR) was calculated using stable isotopes. Furthermore, postprandial plasma concentrations of glucose, insulin, several intestinal hormones and bile acids were analyzed. The structure of FB was considerably more compact compared to CB, as confirmed by microscopy, XRT analysis (porosity) and density measurements. Consumption of FB resulted in lower peak glucose, insulin and glucose-dependent insulinotropic polypeptide (ns) responses and a slower initial RaE compared to CB. These variables were similar to the PA response, except for RaE which remained slower over a longer period after PA consumption. Interestingly, the GCR after FB was higher than expected based on the insulin response, indicating increased insulin sensitivity or insulin-independent glucose disposal. These results demonstrate that the structure of wheat bread can influence the postprandial metabolic response, with a more compact structure being more beneficial for health. Bread-making technology should be further explored to create healthier products.

  9. Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y)

    Nieuwenhuizen, W.; Voskuilen, M.; Hermans, J.

    1982-01-01

    The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the

  10. Fibrates suppress fibrinogen gene expression in rodents via activation of the peroxisome proliferator-activated receptor-α

    Kockx, M.; Gervois, P.P.; Poulain, P.; Derudas, B.; Peters, J.M.; Gonzalez, F.J.; Princen, H.M.G.; Kooistra, T.; Staels, B.

    1999-01-01

    Plasma fibrinogen levels have been identified as an important risk factor for cardiovascular diseases. Among the few compounds known to lower circulating fibrinogen levels in humans are certain fibrates. We have studied the regulation of fibrinogen gene expression by fibrates in rodents. Treatment

  11. L-carnitine: a partner between immune response and lipid metabolism ?

    Giuseppe Famularo

    1993-01-01

    Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

  12. Humoral and cell-mediated immune responses to influenza vaccination in equine metabolic syndrome (EMS) horses.

    Elzinga, Sarah; Reedy, Stephanie; Barker, Virginia D; Chambers, Thomas M; Adams, Amanda A

    2018-05-01

    Obesity is an increasing problem in the equine population with recent reports indicating that the percentage of overweight horses may range anywhere from 20.6-51%. Obesity in horses has been linked to more serious health concerns such as equine metabolic syndrome (EMS). EMS is a serious problem in the equine industry given its defining characteristics of insulin dysregualtion and obesity, as well as the involvement of laminitis. Little research however has been conducted to determine the effects of EMS on routine healthcare of these horses, in particular how they respond to vaccination. It has been shown that obese humans and mice have decreased immune responses to vaccination. EMS may have similar effects on vaccine responses in horses. If this is the case, these animals may be more susceptible to disease, acting as unknown disease reservoirs. Therefore, we investigated the effects of EMS on immune responses to routine influenza vaccination. Twenty-five adult horses of mixed-sex and mixed-breed (8-21 years old) horses; 13 EMS and 12 non-EMS were selected. Within each group, 4 horses served as non-vaccinate saline controls and the remaining horses were vaccinated with a commercially available equine influenza vaccine. Vaccination (influenza or saline) was administered on weeks 0 and 3, and peripheral blood samples taken on week 0 prior to vaccination and on weeks 1, 2, 3, 4, and 5 post vaccination. Blood samples were used to measure hemagglutination inhibition (HI) titers and equine influenza specific IgGa, IgGb, and IgGT levels. Blood samples were also used to isolate peripheral blood mononuclear cells (PBMCs) for analysis of cell mediated immune (CMI) responses via real-time polymerase chain reaction (RT-PCR). All horses receiving influenza vaccination responded with significant increases (P equine influenza specific antibodies following vaccination compared to saline controls. EMS did not significantly affect (P > 0.05) humoral immune responses as measured

  13. Type 2 responses at the interface between immunity and fat metabolism.

    Odegaard, Justin I; Chawla, Ajay

    2015-10-01

    Adipose tissue resident leukocytes are often cast solely as the effectors of obesity and its attendant pathologies; however, recent observations have demonstrated that these cells support and effect 'healthy' physiologic function as well as pathologic dysfunction. Importantly, these two disparate outcomes are underpinned by similarly disparate immune programs; type 2 responses instruct and promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In this Review, we summarize the literature regarding type 2 immunity's role in adipose tissue physiology and allude to its potential therapeutic implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Metabolic responses of primary and transformed cells to intracellular Listeria monocytogenes.

    Nadine Gillmaier

    Full Text Available The metabolic response of host cells, in particular of primary mammalian cells, to bacterial infections is poorly understood. Here, we compare the carbon metabolism of primary mouse macrophages and of established J774A.1 cells upon Listeria monocytogenes infection using (13C-labelled glucose or glutamine as carbon tracers. The (13C-profiles of protein-derived amino acids from labelled host cells and intracellular L. monocytogenes identified active metabolic pathways in the different cell types. In the primary cells, infection with live L. monocytogenes increased glycolytic activity and enhanced flux of pyruvate into the TCA cycle via pyruvate dehydrogenase and pyruvate carboxylase, while in J774A.1 cells the already high glycolytic and glutaminolytic activities hardly changed upon infection. The carbon metabolism of intracellular L. monocytogenes was similar in both host cells. Taken together, the data suggest that efficient listerial replication in the cytosol of the host cells mainly depends on the glycolytic activity of the hosts.

  15. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses.

    Ou, Yang; Wang, Shang-Jui; Li, Dawei; Chu, Bo; Gu, Wei

    2016-11-01

    Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N 1 -acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9-mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

  16. Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

    Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

    2017-02-01

    General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

  17. Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

    Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

    2016-09-02

    To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

  18. Cardiovascular and Metabolic Responses to the Ingestion of Caffeinated Herbal Tea: Drink It Hot or Cold?

    Maufrais, Claire; Sarafian, Delphine; Dulloo, Abdul; Montani, Jean-Pierre

    2018-01-01

    Aim: Tea is usually consumed at two temperatures (as hot tea or as iced tea). However, the importance of drink temperature on the cardiovascular system and on metabolism has not been thoroughly investigated. The purpose of this study was to compare the cardiovascular, metabolic and cutaneous responses to the ingestion of caffeinated herbal tea (Yerba Mate) at cold or hot temperature in healthy young subjects. We hypothesized that ingestion of cold tea induces a higher increase in energy expenditure than hot tea without eliciting any negative effects on the cardiovascular system. Methods: Cardiovascular, metabolic and cutaneous responses were analyzed in 23 healthy subjects (12 men and 11 women) sitting comfortably during a 30-min baseline and 90 min following the ingestion of 500 mL of an unsweetened Yerba Mate tea ingested over 5 min either at cold (~3°C) or hot (~55°C) temperature, according to a randomized cross-over design. Results: Averaged over the 90 min post-drink ingestion and compared to hot tea, cold tea induced (1) a decrease in heart rate (cold tea: -5 ± 1 beats.min -1 ; hot tea: -1 ± 1 beats.min -1 , p hot tea: +3.7%, p hot tea while decreasing cardiac load as suggested by the decrease in the double product. Further experiments are needed to evaluate the clinical impact of unsweetened caffeinated herbal tea at a cold temperature for weight control.

  19. Diurnal changes in CN metabolism and response of rice seedlings to UV-B radiation.

    Yun, Hyejin; Lim, Sunhyung; Kim, Yangmin X; Lee, Yejin; Lee, Seulbi; Lee, Deogbae; Park, Keewoong; Sung, Jwakyung

    2018-03-13

    Plants regulate a number of primary metabolites, including carbohydrates, organic acids, and amino acids, in response to UV-B radiation. Therefore, it is essential to understand the time-dependent response of rice plants to UV-B stress. This study focused on the response of plants to UV-B at different leaf developmental phases (emerging, growing, and maturing) in an attempt to fully comprehend the metabolic shift. We analyzed the expression levels of genes related to starch/sucrose metabolism in the leaf blades of rice seedlings (Oryza sativa L. "Saechuchenog") exposed to UV-B irradiation for short (1 day) and long terms (5 days) using quantitative real-time polymerase chain reaction. We also examined the diurnal variations in the contents of primary metabolites using an established GCTOF-MS (gas chromatography time of flight-mass spectrometry) method. The results showed that the levels of primary metabolites were largely dependent upon the diurnal rhythm and leaf developmental phase. The young leaves (sink) produced and accumulated starch rather than sucrose. The short-term (4 h, 1 day) UV-B exposure inhibited sucrose synthesis, which could be the first target of UV-B radiation. Following short- and long-term (5 days) exposure to UV-B radiation, the dynamic response of primary metabolites was evaluated. It was found that the content of carbohydrates decreased throughout the period of exposure to UV-B stress, especially in terms of sucrose concentration. However, the content of the majority of amino acids increased after an early decrease. Our data revealed that the metabolic response, as well as the gene expression, differed with the period (intensity) of exposure to UV-B radiation and with the phase of leaf development. These findings provide new insights for a better understanding of the metabolic response of a variety of plant species exposed to a wide range of UV-B radiation. Copyright © 2018. Published by Elsevier GmbH.

  20. Responses of the metabolism of the larvae of Pocillopora damicornis to ocean acidification and warming.

    Emily B Rivest

    Full Text Available Ocean acidification and warming are expected to threaten the persistence of tropical coral reef ecosystems. As coral reefs face multiple stressors, the distribution and abundance of corals will depend on the successful dispersal and settlement of coral larvae under changing environmental conditions. To explore this scenario, we used metabolic rate, at holobiont and molecular levels, as an index for assessing the physiological plasticity of Pocillopora damicornis larvae from this site to conditions of ocean acidity and warming. Larvae were incubated for 6 hours in seawater containing combinations of CO2 concentration (450 and 950 µatm and temperature (28 and 30°C. Rates of larval oxygen consumption were higher at elevated temperatures. In contrast, high CO2 levels elicited depressed metabolic rates, especially for larvae released later in the spawning period. Rates of citrate synthase, a rate-limiting enzyme in aerobic metabolism, suggested a biochemical limit for increasing oxidative capacity in coral larvae in a warming, acidifying ocean. Biological responses were also compared between larvae released from adult colonies on the same day (cohorts. The metabolic physiology of Pocillopora damicornis larvae varied significantly by day of release. Additionally, we used environmental data collected on a reef in Moorea, French Polynesia to provide information about what adult corals and larvae may currently experience in the field. An autonomous pH sensor provided a continuous time series of pH on the natal fringing reef. In February/March, 2011, pH values averaged 8.075 ± 0.023. Our results suggest that without adaptation or acclimatization, only a portion of naïve Pocillopora damicornis larvae may have suitable metabolic phenotypes for maintaining function and fitness in an end-of-the century ocean.

  1. Metabolic response of Geobacter sulfurreducens towards electron donor/acceptor variation

    Lovley Derek R

    2010-11-01

    Full Text Available Abstract Background Geobacter sulfurreducens is capable of coupling the complete oxidation of organic compounds to iron reduction. The metabolic response of G. sulfurreducens towards variations in electron donors (acetate, hydrogen and acceptors (Fe(III, fumarate was investigated via 13C-based metabolic flux analysis. We examined the 13C-labeling patterns of proteinogenic amino acids obtained from G. sulfurreducens cultured with 13C-acetate. Results Using 13C-based metabolic flux analysis, we observed that donor and acceptor variations gave rise to differences in gluconeogenetic initiation, tricarboxylic acid cycle activity, and amino acid biosynthesis pathways. Culturing G. sulfurreducens cells with Fe(III as the electron acceptor and acetate as the electron donor resulted in pyruvate as the primary carbon source for gluconeogenesis. When fumarate was provided as the electron acceptor and acetate as the electron donor, the flux analysis suggested that fumarate served as both an electron acceptor and, in conjunction with acetate, a carbon source. Growth on fumarate and acetate resulted in the initiation of gluconeogenesis by phosphoenolpyruvate carboxykinase and a slightly elevated flux through the oxidative tricarboxylic acid cycle as compared to growth with Fe(III as the electron acceptor. In addition, the direction of net flux between acetyl-CoA and pyruvate was reversed during growth on fumarate relative to Fe(III, while growth in the presence of Fe(III and acetate which provided hydrogen as an electron donor, resulted in decreased flux through the tricarboxylic acid cycle. Conclusions We gained detailed insight into the metabolism of G. sulfurreducens cells under various electron donor/acceptor conditions using 13C-based metabolic flux analysis. Our results can be used for the development of G. sulfurreducens as a chassis for a variety of applications including bioremediation and renewable biofuel production.

  2. Fibrinogen-Induced Streptococcus mutans Biofilm Formation and Adherence to Endothelial Cells

    Telma Blanca Lombardo Bedran

    2013-01-01

    Full Text Available Streptococcus mutans, the predominant bacterial species associated with dental caries, can enter the bloodstream and cause infective endocarditis. The aim of this study was to investigate S. mutans biofilm formation and adherence to endothelial cells induced by human fibrinogen. The putative mechanism by which biofilm formation is induced as well as the impact of fibrinogen on S. mutans resistance to penicillin was also evaluated. Bovine plasma dose dependently induced biofilm formation by S. mutans. Of the various plasma proteins tested, only fibrinogen promoted the formation of biofilm in a dose-dependent manner. Scanning electron microscopy observations revealed the presence of complex aggregates of bacterial cells firmly attached to the polystyrene support. S. mutans in biofilms induced by the presence of fibrinogen was markedly resistant to the bactericidal effect of penicillin. Fibrinogen also significantly increased the adherence of S. mutans to endothelial cells. Neither S. mutans cells nor culture supernatants converted fibrinogen into fibrin. However, fibrinogen is specifically bound to the cell surface of S. mutans and may act as a bridging molecule to mediate biofilm formation. In conclusion, our study identified a new mechanism promoting S. mutans biofilm formation and adherence to endothelial cells which may contribute to infective endocarditis.

  3. Clumping factor A-mediated virulence during Staphylococcus aureus infection is retained despite fibrinogen depletion.

    Palmqvist, Niklas; Josefsson, Elisabet; Tarkowski, Andrzej

    2004-02-01

    Clumping factor A (ClfA), a fibrinogen-binding protein expressed on the Staphylococcus aureus cell surface, has previously been shown to act as a virulence factor in experimental septic arthritis. Although the interaction between ClfA and fibrinogen is assumed to be of importance for the virulence of S. aureus, this has not been demonstrated in any in vivo model of infection. Therefore, the objective of this study was to investigate the contribution of this interaction to ClfA-mediated virulence in murine S. aureus-induced arthritis. Ancrod, a serine protease with thrombin-like activity, was used to induce in vivo depletion of fibrinogen in mice. Ancrod treatment significantly aggravated septic arthritis following inoculation with a ClfA-expressing strain (Newman) compared to control treatment. Also, ancrod treatment tended to enhance the arthritis induced by a clfA mutant strain (DU5876), indicating that fibrinogen depletion exacerbates septic arthritis in a ClfA-independent manner. Most importantly, the ClfA-expressing strain was much more arthritogenic than the isogenic clfA mutant, following inoculation of fibrinogen-depleted mice. This finding indicates that the interaction between ClfA and free fibrinogen is not required for ClfA-mediated functions contributing to S. aureus virulence. It is conceivable that ClfA contributes to the virulence of S. aureus through interactions with other host ligands than fibrinogen.

  4. A randomized, double blind trial of prophylactic fibrinogen to reduce bleeding in cardiac surgery

    Mostafa Sadeghi

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVES: Postoperative bleeding has a great clinical importance and can contribute to increased mortality and morbidity in patients undergoing coronary artery bypass graft surgery. In this prospective, randomized, double-blind study, we evaluated the effect of prophylactic administration of fibrinogen concentrate on post-coronary artery bypass graft surgery bleeding. METHODS: A total of 60 patients undergoing coronary artery bypass surgery were randomly divided into two groups. Patients in the fibrinogen group received 1 g of fibrinogen concentrate 30 min prior to the operation, while patients in the control group received placebo. Post-operative bleeding volumes, prothrombin time, partial thromboplastin time, INR, hemoglobin and transfused blood products in both groups were recorded. A strict red blood cell transfusion protocol was used in all patients. RESULTS: There were no significant differences between intra-operative packed red blood cells infusion in the studied groups (1.0 ± 1.4 in fibrinogen group, and 1.3 ± 1.1 in control group. Less postoperative bleeding was observed in the fibrinogen group (477 ± 143 versus 703 ± 179, p = 0.0001. Fifteen patients in the fibrinogen group and 21 in the control group required post-op packed red blood cells infusion (p = 0.094. No thrombotic event was observed through 72 h after surgery. CONCLUSION: Prophylactic fibrinogen reduces post-operative bleeding in patients undergoing coronary artery bypass graft.

  5. Metabolic Responses and Pacing Strategies during Successive Sprint Skiing Time Trials

    Andersson, Erik; Holmberg, Hans-Christer; Ørtenblad, Niels

    2016-01-01

    PURPOSE: To examine the metabolic responses and pacing strategies during the performance of successive sprint time trials (STTs) in cross-country skiing. METHODS: Ten well-trained male cross-country skiers performed four self-paced 1300-m STTs on a treadmill, each separated by 45 min of recovery...... to estimate the anaerobic energy supply. RESULTS: The individual trial-to-trial variability in STT performance time was 1.3%, where variations in O2 deficit and V˙O2 explained 69% (P 0.05) of the variation in performance. The first and last STTs were equally fast (228 ± 10 s), and ~ 1...... on the first than second course half. In addition, metabolic rates were substantially higher (~_30%) for uphill than for flat skiing, indicating that pacing was regulated to the terrain. CONCLUSIONS: The fastest STTs were characterized primarily by a greater anaerobic energy production, which also explained 69...

  6. Deposition of fibrinogen on the surface of in vitro thrombi prevents platelet adhesion.

    Owaynat, Hadil; Yermolenko, Ivan S; Turaga, Ramya; Lishko, Valeryi K; Sheller, Michael R; Ugarova, Tatiana P

    2015-12-01

    The initial accumulation of platelets after vessel injury is followed by thrombin-mediated generation of fibrin which is deposited around the plug. While numerous in vitro studies have shown that fibrin is highly adhesive for platelets, the surface of experimental thrombi in vivo contains very few platelets suggesting the existence of natural anti-adhesive mechanisms protecting stabilized thrombi from platelet accumulation and continuous thrombus propagation. We previously showed that adsorption of fibrinogen on pure fibrin clots results in the formation of a nonadhesive matrix, highlighting a possible role of this process in surface-mediated control of thrombus growth. However, the deposition of fibrinogen on the surface of blood clots has not been examined. In this study, we investigated the presence of intact fibrinogen on the surface of fibrin-rich thrombi generated from flowing blood and determined whether deposited fibrinogen is nonadhesive for platelets. Stabilized fibrin-rich thrombi were generated using a flow chamber and the time that platelets spend on the surface of thrombi was determined by video recording. The presence of fibrinogen and fibrin on the surface of thrombi was analyzed by confocal microscopy using specific antibodies. Examination of the spatial distribution of two proteins revealed the presence of intact fibrinogen on the surface of stabilized thrombi. By manipulating the surface of thrombi to display either fibrin or intact fibrinogen, we found that platelets adhere to fibrin- but not to fibrinogen-coated thrombi. These results indicate that the fibrinogen matrix assembled on the outer layer of stabilized in vitro thrombi protects them from platelet adhesion. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients.

    Aziz, Hafsa; Gill, Uzma; Raza, Abida; Gill, Muzaffar L

    2014-05-01

    Hepatitis C viral (HCV) infection is caused by an RNA virus. HCV infection is considered to induce systemic disease that causes steatosis, alters lipid metabolism, and results in metabolic syndrome. This study aimed to investigate the therapeutic outcome in HCV genotype 3 patients with metabolic syndrome. A total of 621 HCV-positive patients who visited the hospital for treatment were screened. Among these, 441 patients were enrolled for antiviral therapy. These enrolled patients were assessed for metabolic syndrome according to the International Diabetes Federation criteria. Group A included patients with metabolic syndrome and group B included patients without metabolic syndrome. All patients received peginterferon-α2a (180 μg/week) and ribavirin (10 mg/kg/day) for 6 months. The prevalence of metabolic syndrome in chronic HCV patients was 37.9%. We observed that metabolic syndrome was more common among female compared with male participants (43.9 vs. 28.8%, P=0.005). It was found that sustained virologic response (SVR) rates were significantly higher in the patients in group B (without metabolic syndrome) compared with the patients in group A who had metabolic syndrome (72.2 vs. 43.7%, Pmetabolic syndrome and a correlation of metabolic syndrome with nonresponse to antiviral therapy was observed. An interesting correlation among metabolic syndrome, age, and SVR was found: with age, SVR decreases, while metabolic syndrome increases. Metabolic syndrome has an influence on therapeutic outcomes in terms of SVR. Moreover, this information can identify patients who might have a low chance of attaining an SVR and a timely decision may protect the patients from the adverse effects of therapy.

  8. Radio-iodination of a rabbit fibrinogen by the chloramine-T method

    Moza, A K; Kumar, M; Belavalgidad, M I; Sapru, R P [Post-Graduate Inst. of Medical Education and Research, Chandigarh (India). Dept. of Experimental Medicine

    1974-01-01

    A method for radio-iodination of fibrinogen using chloramine-T has been described. Samples of greater than 90% clottable counts were obtained. Electrophoretic mobility and immunodiffusion showed that the entire radioactivity was present in the fibrinogen band. In vivo studies on the turnover of this labelled product in rabbits showed a half-life of 52.8 to 61.7 hrs in two batches of animals. The results compare very well with the reported results obtained from fibrinogen labelled with radioactive iodine by the iodine-monochloride method. The advantages of the new method have been pointed out.

  9. Distribution of iodine-labelled fibrinogen in rat during endotoxin shock

    Toth, J [Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary); Spett, B; Bertok, L; Kocsar, L [Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, Budapest (Hungary)

    1978-10-01

    Animals of the experimental and control groups received 10-10 microcurie i.v. /sup 125/I-fibrinogen. The fibrinogen forms a deposit on the surface of the microthrombi and we can find more activity where the thrombi were formed. 60 minutes after administering endotoxin the activity of the ilium of the shocked animals increased significantly (exceeding that of the control group by 37%). A considerable difference may be observed also 120 minutes later, and the activity of the liver amounts to twice the activity of control animals two hours after i.v. /sup 125/I-fibrinogen injection.

  10. Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

    Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

    1986-01-01

    Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

  11. Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

    Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

    2016-08-01

    Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. The effect of metabolic alkalosis on the ventilatory response in healthy subjects.

    Oppersma, E; Doorduin, J; van der Hoeven, J G; Veltink, P H; van Hees, H W H; Heunks, L M A

    2018-02-01

    Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation. In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days. Plasma bicarbonate increased from 25.2 ± 2.2 to 29.2 ± 1.9 mmol/L. With increasing inspiratory CO 2 pressure during the HCVR test, RR, V t , Pdi, EAdi and V E increased. The clinical ratio ΔV E /ΔP et CO 2 remained unchanged, but Pdi, EAdi and V E were significantly lower after bicarbonate administration for similar levels of inspired CO 2 . This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO 2 . Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Global host metabolic response to Plasmodium vivax infection: a 1H NMR based urinary metabonomic study

    Sengupta Arjun

    2011-12-01

    Full Text Available Abstract Background Plasmodium vivax is responsible for the majority of malarial infection in the Indian subcontinent. This species of the parasite is generally believed to cause a relatively benign form of the disease. However, recent reports from different parts of the world indicate that vivax malaria can also have severe manifestation. Host response to the parasite invasion is thought to be an important factor in determining the severity of manifestation. In this paper, attempt was made to determine the host metabolic response associated with P. vivax infection by means of NMR spectroscopy-based metabonomic techniques in an attempt to better understand the disease pathology. Methods NMR spectroscopy of urine samples from P. vivax-infected patients, healthy individuals and non-malarial fever patients were carried out followed by multivariate statistical analysis. Two data analysis techniques were employed, namely, Principal Component Analysis [PCA] and Orthogonal Projection to Latent Structure Discriminant Analysis [OPLS-DA]. Several NMR signals from the urinary metabolites were further selected for univariate comparison among the classes. Results The urine metabolic profiles of P. vivax-infected patients were distinct from those of healthy individuals as well as of non-malarial fever patients. A highly predictive model was constructed from urine profile of malarial and non-malarial fever patients. Several metabolites were found to be varying significantly across these cohorts. Urinary ornithine seems to have the potential to be used as biomarkers of vivax malaria. An increasing trend in pipecolic acid was also observed. The results suggest impairment in the functioning of liver as well as impairment in urea cycle. Conclusions The results open up a possibility of non-invasive analysis and diagnosis of P. vivax using urine metabolic profile. Distinct variations in certain metabolites were recorded, and amongst these, ornithine may have the

  14. Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity

    Kant, Shashi; Barrett, Tamera; Vertii, Anastassiia; Noh, Yun Hee; Jung, Dae Young; Kim, Jason K.; Davis, Roger J.

    2013-01-01

    Saturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that l...

  15. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    Yates, D. T.; Macko, A. R.; Nearing, M.; Chen, X.; Rhoads, R. P.; Limesand, S. W.

    2012-01-01

    Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization. PMID:22900186

  16. Energetic and metabolic transient response of Saccharomyces cerevisiae to benzoic acid.

    Kresnowati, M T A P; van Winden, W A; van Gulik, W M; Heijnen, J J

    2008-11-01

    Saccharomyces cerevisiae is known to be able to adapt to the presence of the commonly used food preservative benzoic acid with a large energy expenditure. Some mechanisms for the adaptation process have been suggested, but its quantitative energetic and metabolic aspects have rarely been discussed. This study discusses use of the stimulus response approach to quantitatively study the energetic and metabolic aspects of the transient adaptation of S. cerevisiae to a shift in benzoic acid concentration, from 0 to 0.8 mM. The information obtained also serves as the basis for further utilization of benzoic acid as a tool for targeted perturbation of the energy system, which is important in studying the kinetics and regulation of central carbon metabolism in S. cerevisiae. Using this experimental set-up, we found significant fast-transient (< 3000 s) increases in O(2) consumption and CO(2) production rates, of approximately 50%, which reflect a high energy requirement for the adaptation process. We also found that with a longer exposure time to benzoic acid, S. cerevisiae decreases the cell membrane permeability for this weak acid by a factor of 10 and decreases the cell size to approximately 80% of the initial value. The intracellular metabolite profile in the new steady-state indicates increases in the glycolytic and tricarboxylic acid cycle fluxes, which are in agreement with the observed increases in specific glucose and O(2) uptake rates.

  17. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    D. T. Yates

    2012-01-01

    Full Text Available Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR, skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.

  18. Tributyltin toxicity in abalone (Haliotis diversicolor supertexta) assessed by antioxidant enzyme activity, metabolic response, and histopathology.

    Zhou, Jin; Zhu, Xiao-shan; Cai, Zhong-hua

    2010-11-15

    A toxicity test was performed to investigate the possible harmful effects of tributyltin (TBT) on abalone (Haliotis diversicolor supertexta). Animals were exposed to TBT in a range of environmentally relevant concentrations (2, 10 and 50 ng/L) for 30 days under laboratory conditions. TBT-free conditions were used as control treatments. The activity of antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA), along with levels of haemolymph metabolites, and hepatopancreas histopathology were analyzed. The results showed that TBT decreased SOD activity, and increased POD level and MDA production in a dose-dependent way, indicating that oxidative injury was induced by TBT. Haemolymph metabolite measurements showed that TBT increased alanine and glutamate levels, and decreased glucose content, which suggested perturbation of energy metabolism. Elevated levels of acetate and pyruvate in the haemolymph indicated partial alteration of lipid metabolism. A decrease in lactate and an increase in succinate, an intermediate of the tricarboxylic acid (TCA) cycle, indicated disturbance of amino acid metabolism. Hepatopancreas tissues also exhibited inflammatory responses characterized by histopathological changes such as cell swelling, granular degeneration, and inflammation. Taken together, these results demonstrated that TBT was a potential toxin with a variety of deleterious effects on abalone. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Responsive eLearning exercises to enhance student interaction with metabolic pathways.

    Roesler, William J; Dreaver-Charles, Kristine

    2018-05-01

    Successful learning of biochemistry requires students to engage with the material. In the past this often involved students writing out pathways by hand, and more recently directing students to online resources such as videos, songs, and animated slide presentations. However, even these latter resources do not really provide students an opportunity to engage with the material in an active fashion. As part of an online introductory metabolism course that was developed at our university, we created a series of twelve online interactive activities using Adobe Captivate 9. These activities targeted glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogen metabolism, the citric acid cycle, and fatty acid oxidation. The interactive exercises consisted of two types. One involved dragging objects such as names of enzymes or allosteric modifiers to their correct drop locations such as a particular point in a metabolic pathway, a specific enzyme, and so forth. A second type involved clicking on objects, locations within a pathway, and so forth, in response to a particular question. In both types of exercises, students received feedback on their decisions in order to enhance learning. The student feedback received on these activities was very positive, and indicated that they found them to increase their confidence in the material and that they had learned the key principles of each pathway. © 2018 by The International Union of Biochemistry and Molecular Biology, 46(3):223-229, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

  20. Metabolic Profiling of Dendrobium officinale in Response to Precursors and Methyl Jasmonate

    Chunyan Jiao

    2018-03-01

    Full Text Available Alkaloids are the main active ingredients in the medicinal plant Dendrobium officinale. Based on the published genomic and transcriptomic data, a proposed terpenoid indole alkaloid (TIA biosynthesis pathway may be present in D. officinale. In this study, protocorm-like bodies (PLBs with a high-yielding production of alkaloids were obtained by the optimization of tryptophan, secologanin and methyl jasmonate (MeJA treatment. The results showed that the total alkaloid content was 2.05 times greater than that of the control group when the PLBs were fed with 9 µM tryptophan, 6 µM secologanin and 100 µM MeJA after 36 days. HPLC analysis showed that strictosidine synthase (STR activity also increased in the treated plants. A total of 78 metabolites were identified using gas chromatography-mass spectrometry (GC-MS in combination with liquid chromatography-mass spectrometry (LC-MS methods; 29 differential metabolites were identified according to the multivariate statistical analysis. Among them, carapanaubine, a kind of TIA, exhibited dramatically increased levels. In addition, a possible underlying process of the metabolic flux from related metabolism to the TIA biosynthetic pathway was enhanced. These results provide a comprehensive view of the metabolic changes related to alkaloid biosynthesis, especially TIA biosynthesis, in response to tryptophan, secologanin and MeJA treatment.

  1. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  2. Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

    Mariana Schroeder

    2018-03-01

    Full Text Available Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals. Objective: We attempted to address the issue of individual differences in the response to weight cycling in male mice. Methods: We first exposed adult wild type mice to repeated cycles of high/low fat food. Next, using a lentiviral approach, we knocked-down or over-expressed miR-219 in the ventromedial hypothalamus (VMH of an additional mouse cohort and performed a full metabolic assessment. Results: Exposure of wild type males to weight cycling resulted in the division of the cohort into subsets of resistant versus metabolic-syndrome-prone (MS animals, which differed in their metabolic profile and hypothalamic miR-219 levels. Lentiviral knock-down of miR-219 in the VMH led to exacerbation of metabolic syndrome. In contrast, over-expression of miR-219 resulted in moderation of the metabolic syndrome phenotype. Conclusions: Our results suggest a role for miR-219 in the mediation of the metabolic phenotype resulting from repeated weight cycling. Keywords: Weight cycling, Metabolic syndrome, miRNAs, Ventromedial hypothalamus, High fat diet, Diabetes

  3. The β fibrinogen gene G-455A polymorphism in Asian subjects with ...

    Jonny Karunia Fajar

    2016-08-10

    Aug 10, 2016 ... Conclusions: In the Asian population, the b fibrinogen gene G-455A polymorphism was associ- ..... Kazakhstan, Kuwait, Kyrgyzstan, Laos, Lebanon, Malaysia, ... Thailand, Timor-Leste, Turkey, Turkmenistan, United Arab.

  4. Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy

    Hansen, Anette Tarp; Andreasen, Birgitte Horst; Salvig, Jannie Dalby

    2010-01-01

    Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference...... intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women...... in gestational week 11–17, with normal current pregnancy. Blood samples were collected in gestational weeks 11–17, 21–27 and 34–37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution®. Results. A significant rise in D-dimer was found from first to second trimester (p...

  5. Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial.

    Ducloy-Bouthors, Anne-Sophie; Mignon, Alexandre; Huissoud, Cyril; Grouin, Jean-Marie; Mercier, Frédéric J

    2016-08-01

    Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH. The FIDEL trial objective is to evaluate the impact of a therapeutic strategy based on the early administration of human fibrinogen concentrate compared to the current practice based on late administration in severe PPH patients requiring second line uterotonics. This is a prospective multicentre, randomised, double-blind, placebo-controlled trial. A total of 412 patients will be randomised if they meet the following criteria: female patients≥18 years old, vaginal delivery, PPH requiring IV administration of prostaglandins (sulprostone) after 20 to 30minutes of oxytocin failure. The participants are assigned to receive either fibrinogen 3g or placebo infusions. The primary endpoint is a composite endpoint defined as the percentage of patients losing at least 4g/dL of Hb, and/or requiring a transfusion of at least 2 units of packed red blood cells, within the 48hours following fibrinogen administration. The purpose of this study is to demonstrate the efficacy and safety of an early fibrinogen concentrate infusion in uncontrolled active PPH. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  6. Mechanical and Metabolic Responses to Traditional and Cluster Set Configurations in the Bench Press Exercise.

    García-Ramos, Amador; González-Hernández, Jorge M; Baños-Pelegrín, Ezequiel; Castaño-Zambudio, Adrián; Capelo-Ramírez, Fernando; Boullosa, Daniel; Haff, Guy G; Jiménez-Reyes, Pedro

    2017-10-20

    García-Ramos, A, González-Hernández, JM, Baños-Pelegrín, E, Castaño-Zambudio, A, Capelo-Ramírez, F, Boullosa, D, Haff, GG, and Jiménez-Reyes, P. Mechanical and metabolic responses to traditional and cluster set configurations in the bench press exercise. J Strength Cond Res XX(X): 000-000, 2017-This study aimed to compare mechanical and metabolic responses between traditional (TR) and cluster (CL) set configurations in the bench press exercise. In a counterbalanced randomized order, 10 men were tested with the following protocols (sets × repetitions [inter-repetition rest]): TR1: 3 × 10 (0-second), TR2: 6 × 5 (0-second), CL5: 3 × 10 (5-second), CL10: 3 × 10 (10-second), and CL15: 3 × 10 (15-second). The number of repetitions (30), interset rest (5 minutes), and resistance applied (10 repetition maximum) were the same for all set configurations. Movement velocity and blood lactate concentration were used to assess the mechanical and metabolic responses, respectively. The comparison of the first and last set of the training session revealed a significant decrease in movement velocity for TR1 (Effect size [ES]: -0.92), CL10 (ES: -0.85), and CL15 (ES: -1.08) (but not for TR2 [ES: -0.38] and CL5 [ES: -0.37]); while blood lactate concentration was significantly increased for TR1 (ES: 1.11), TR2 (ES: 0.90), and CL5 (ES: 1.12) (but not for CL10 [ES: 0.03] and CL15 [ES: -0.43]). Based on velocity loss, set configurations were ranked as follows: TR1 (-39.3 ± 7.3%) > CL5 (-20.2 ± 14.7%) > CL10 (-12.9 ± 4.9%), TR2 (-10.3 ± 5.3%), and CL15 (-10.0 ± 2.3%). The set configurations were ranked as follows based on the lactate concentration: TR1 (7.9 ± 1.1 mmol·L) > CL5 (5.8 ± 0.9 mmol·L) > TR2 (4.2 ± 0.7 mmol·L) > CL10 (3.5 ± 0.4 mmol·L) and CL15 (3.4 ± 0.7 mmol·L). These results support the use of TR2, CL10, and CL15 for the maintenance of high mechanical outputs, while CL10 and CL15 produce less metabolic stress than TR2.

  7. A single night light exposure acutely alters hormonal and metabolic responses in healthy participants

    Mohammed S Albreiki

    2017-01-01

    Full Text Available Many animal studies have reported an association between melatonin suppression and the disturbance of metabolic responses; yet, few human studies have investigated bright light effects on metabolic and hormonal responses at night. This study investigated the impact of light on plasma hormones and metabolites prior to, and after, an evening meal in healthy participants. Seventeen healthy participants, 8 females (22.2 ± 2.59 years, mean ± s.d. and 9 males (22.8 ± 3.5 years were randomised to a two-way cross-over design protocol; dim light (DL (500 lux sessions, separated by at least seven days. Saliva and plasma samples were collected prior to and after a standard evening meal at specific intervals. Plasma non-esterified fatty acid (NEFA levels were significantly higher pre-meal in DL compared to BL (P < 0.01. Plasma glucose and insulin levels were significantly greater post-meal in the BL compared to DL session (P = 0.02, P = 0.001, respectively. Salivary melatonin levels were significantly higher in the DL compared to those in BL session (P = 0.005. BL at night was associated with significant increases in plasma glucose and insulin suggestive of glucose intolerance and insulin insensitivity. Raised pre-prandial NEFA levels may be due to changes in insulin sensitivity or the presence of melatonin and/or light at night. Plasma triglyceride (TAG levels were the same in both sessions. These results may explain some of the health issues reported in shift workers; however, further studies are needed to elucidate the cause of these metabolic changes.

  8. Metabolic responses of the Antarctic fishes Notothenia rossii and Notothenia coriiceps to sewage pollution.

    Rodrigues, Edson; Feijó-Oliveira, Mariana; Suda, Cecília Nohome Kawagoe; Vani, Gannabathula Sree; Donatti, Lucélia; Rodrigues, Edson; Lavrado, Helena Passeri

    2015-10-01

    The present study aimed to assess the sewage effects of the Brazilian Antarctic Station Comandante Ferraz, Admiralty Bay, King George Island, on the hepatic metabolism (energetic, antioxidant, and arginase levels) and levels of plasma constituents of two Antarctic fish species Notothenia rossii and N. coriiceps. The bioassays were conducted under controlled temperature (0 °C) and salinity (35 psu), exposing the fish for 96 h, to sewage effluent diluted in seawater to 0.5 % (v/v). Liver homogenates were tested for the specific activities of the enzymes glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GPase), hexokinase, citrate synthase, lactate dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, superoxide dismutase, glutathione reductase, catalase, and arginase. Plasma levels of glucose, triacylglycerides, cholesterol, total protein, albumin, chloride, magnesium, calcium, and inorganic phosphate were also determined. In N. rossii, the decrease in citrate synthase and the increase in G6Pase and GPase suggested that the sewage effluent activated glycogenolysis and hepatic gluconeogenesis, whereas is N. coriiceps, only G6Pase levels were increased. In N. rossii, sewage effluent induced hypertriglyceridemia without modulating glucose plasma levels, in contrast to N. coriiceps, which developed hypoglycemia without elevating plasma triglyceride levels. The decrease in glutathione reductase levels in N. coriiceps and in superoxide dismutase and catalase in N. rossii suggest that these two species are susceptible to oxidative stress stemming from the production of reactive oxygen species. An increase in magnesium in N. rossii and a decrease in N. coriiceps showed that sewage effluent compromised the control of plasma levels of this cation. Although phylogenetically close, both species of Antarctic fish exhibited different metabolic responses to the sewage effluent, with N. coriiceps showing greater susceptibility to the toxic effects of the

  9. Contribution to the study of plasmatic fibrinogen and serum albumin: effects of irradiation

    Suscillon, M.

    1967-01-01

    The author studies the modifications of properties and structure of serum albumin and fibrinogen solution when subjected to radiation of low energy (X rays). On the other hand, two original techniques are exposed: 1. Amperometric determination of fibrin stabilizing factor or factor XIII of hemostasis. 2. Spectrophotometric study of fibrin formation kinetics. Then showing off and quantitative determination of platelets fibrinogen is exposed. (author) [fr

  10. Iodine-labelling of albumin and fibrinogen and application in selecting implantable material-titanium oxide

    Liu Fangyan; Zhou Meiying; Zhang Feng

    1998-01-01

    Human serum albumin and fibrinogen were successfully labelled with 125 I. The labelled proteins were further applied to carry out a background study on the selection of the blood-compatible materials. The protein adsorption of four kinds of titanium oxide film was determined and compared. It was found that Sample B can adsorb more albumin and less fibrinogen than other three samples and hold the adsorbed albumin most stably

  11. Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells

    Bro, Christoffer; Regenberg, Birgitte; Lagniel, G.

    2003-01-01

    Lithium is highly toxic to yeast when grown in galactose medium mainly because phosphoglucomutase, a key enzyme of galactose metabolism, is inhibited. We studied the global protein and gene expression profiles of Saccharomyces cerevisiae grown in galactose in different time intervals after addition...... of lithium. These results were related to physiological studies where both secreted and intracellular metabolites were determined. Microarray analysis showed that 664 open reading frames were down-regulated and 725 up-regulated in response to addition of lithium. Genes involved in transcription, translation......-regulated proteins were also identified as being changed on the mRNA level. Functional clusters obtained from proteome data were coincident with transcriptional clusters. Physiological studies showed that acetate, glycerol, and glycogen accumulate in response to lithium, as reflected in expression data, whereas...

  12. Proteomic Analysis of Metabolic Responses to Biofuels and Chemicals in Photosynthetic Cyanobacteria.

    Sun, T; Chen, L; Zhang, W

    2017-01-01

    Recent progresses in various "omics" technologies have enabled quantitative measurements of biological molecules in a high-throughput manner. Among them, high-throughput proteomics is a rapidly advancing field that offers a new means to quantify metabolic changes at protein level, which has significantly facilitated our understanding of cellular process, such as protein synthesis, posttranslational modifications, and degradation in responding to environmental perturbations. Cyanobacteria are autotrophic prokaryotes that can perform oxygenic photosynthesis and have recently attracted significant attentions as one promising alternative to traditionally biomass-based "microbial cell factories" to produce green fuels and chemicals. However, early studies have shown that the low tolerance to toxic biofuels and chemicals represented one major hurdle for further improving productivity of the cyanobacterial production systems. To address the issue, metabolic responses and their regulation of cyanobacterial cells to toxic end-products need to be defined. In this chapter, we discuss recent progresses in interpreting cyanobacterial responses to biofuels and chemicals using high-throughput proteomics approach, aiming to provide insights and guidelines on how to enhance tolerance and productivity of biofuels or chemicals in the renewable cyanobacteria systems in the future. © 2017 Elsevier Inc. All rights reserved.

  13. Growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus Selenka during periods of inactivity

    Du, Rongbin; Zang, Yuanqi; Tian, Xiangli; Dong, Shuanglin

    2013-03-01

    The growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus, were investigated during periods of inactivity. The body weight, oxygen consumption rate (OCR), activities of acidic phosphatase (ACP), alkaline phosphatase (AKP), catalase (CAT) and superoxide dismutase (SOD), and content of heat shock protein 70 (Hsp70) in the body wall and coelomic fluid of A. japonicus were measured during starvation, experimental aestivation and aestivation. The results showed that the body weight of sea cucumber in the three treatments decreased significantly during the experimental period ( P sea cucumber reduced in starvation and experimental aestivation treatments, but increased gradually in natural aestivation treatment. The activities of ACP and AKP of sea cucumber decreased gradually in all treatments, whereas those of SOD and CAT as well as Hsp70 content decreased in the starvation and experimental aestivation treatments and increased in natural aestivation treatment. The sea cucumber entered a state of aestivation at 24°C. To some extent, the animals in experimental aestivation were different from those in natural aestivation in metabolism and physiological response. These findings suggested that the aestivation mechanism of A. japonicus is complex and may not be attributed to the elevated temperature only.

  14. Correlations of Eisenia fetida metabolic responses to extractable phenanthrene concentrations through time

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda; Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail, Toronto, Ontario, M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.c [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail, Toronto, Ontario, M1C 1A4 (Canada)

    2010-06-15

    Eisenia fetida earthworms were exposed to phenanthrene for thirty days to compare hydroxypropyl-beta-cyclodextrin (HPCD) extraction of soil and {sup 1}H NMR earthworm metabolomics as indicators of bioavailability. The phenanthrene 28-d LC{sub 50} value was 750 mg/kg (632-891, 95% confidence intervals) for the peat soil tested. The initial phenanthrene concentration was 319 mg/kg, which biodegraded to 16 mg/kg within 15 days, at which time HPCD extraction suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of {sup 1}H NMR spectra for E. fetida tissue extracts indicated that phenanthrene exposed and control earthworms differed throughout the 30 day experiment despite the low phenanthrene concentrations present after 15 days. This metabolic response was better correlated to total phenanthrene concentrations (Q{sup 2} = 0.59) than HPCD-extractable phenanthrene concentrations (Q{sup 2} = 0.46) suggesting that {sup 1}H NMR metabolomics offers considerable promise as a novel, molecular-level method to directly monitor the bioavailability of contaminants to earthworms in the environment. - Metabolic responses of Eisenia fetida earthworms to phenanthrene exposure are better correlated to total phenanthrene concentrations than to cyclodextrin-extractable concentrations through time.

  15. Time course of the response of carbohydrate metabolism to unloading of the soleus

    Henriksen, Erik J.; Tischler, Marc E.

    1988-01-01

    The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

  16. Noninvasive presymptomatic detection of Cercospora beticola infection and identification of early metabolic responses in sugar beet

    Hans-Peter Mock

    2016-09-01

    Full Text Available Cercospora beticola is an economically significant fungal pathogen of sugar beet, and is the causative pathogen of Cercospora leaf spot. Selected host genotypes with contrasting degree of susceptibility to the disease have been exploited to characterize the patterns of metabolite responses to fungal infection, and to devise a pre-symptomatic, non-invasive method of detecting the presence of the pathogen. Sugar beet genotypes were analyzed for metabolite profiles and hyperspectral signatures. Correlation of data matrices from both approaches facilitated identification of candidates for metabolic markers. Hyperspectral imaging was highly predictive with a classification accuracy of 98.5-99.9 % in detecting C. beticola. Metabolite analysis revealed metabolites altered by the host as part of a successful defence response: these were L-DOPA, 12-hydroxyjasmonic acid 12-O-β-D-glucoside, pantothenic acid and 5-O-feruloylquinic acid. The accumulation of glucosylvitexin in the resistant cultivar suggests it acts as a constitutively-produced protectant. The study establishes a proof-of-concept for an unbiased, presymptomatic and non-invasive detection system for the presence of C. beticola. The test needs to be validated with a larger set of genotypes, to be scalable to the level of a crop improvement program, aiming to speed up the selection for resistant cultivars of sugar beet. Untargeted metabolic profiling is a valuable tool to identify metabolites which correlate with hyperspectral data.

  17. Correlations of Eisenia fetida metabolic responses to extractable phenanthrene concentrations through time

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda; Simpson, Andre J.; Simpson, Myrna J.

    2010-01-01

    Eisenia fetida earthworms were exposed to phenanthrene for thirty days to compare hydroxypropyl-β-cyclodextrin (HPCD) extraction of soil and 1 H NMR earthworm metabolomics as indicators of bioavailability. The phenanthrene 28-d LC 50 value was 750 mg/kg (632-891, 95% confidence intervals) for the peat soil tested. The initial phenanthrene concentration was 319 mg/kg, which biodegraded to 16 mg/kg within 15 days, at which time HPCD extraction suggested that phenanthrene was no longer bioavailable. Multivariate statistical analysis of 1 H NMR spectra for E. fetida tissue extracts indicated that phenanthrene exposed and control earthworms differed throughout the 30 day experiment despite the low phenanthrene concentrations present after 15 days. This metabolic response was better correlated to total phenanthrene concentrations (Q 2 = 0.59) than HPCD-extractable phenanthrene concentrations (Q 2 = 0.46) suggesting that 1 H NMR metabolomics offers considerable promise as a novel, molecular-level method to directly monitor the bioavailability of contaminants to earthworms in the environment. - Metabolic responses of Eisenia fetida earthworms to phenanthrene exposure are better correlated to total phenanthrene concentrations than to cyclodextrin-extractable concentrations through time.

  18. Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring.

    Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

    2017-01-01

    The mother's consumption of high-fat food can affect glucose metabolism and the hypothalamic-pituitary-adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Female rats were randomly divided into normal and high-fat diet groups and were fed in accordance with their given diets from pre-pregnancy to the end of lactation. The offspring were divided into control (NC and HFC) and stress (NS and HFS) groups based on their mothers' diet and exposure to stress in adulthood. After the two-week stress induction period was over, an intraperitoneal glucose tolerance test (IPGTT) was performed and plasma glucose and insulin levels were assessed. The pancreas was then removed for measuring insulin secretion from the isolated islets as well as glucose transporter 2 mRNA expression and protein levels. According to the results obtained, plasma corticosterone concentrations increased significantly on days 1 and 14 of the stress induction period and were lower on the last day compared to on the first day. In both the NS and HFS groups, stress reduced plasma insulin concentration in the IPGTT without changing the plasma glucose concentration, suggesting an increased insulin sensitivity in the NS and HFS groups, although more markedly in the latter. Stress reduced insulin secretion (at high glucose concentrations) and increased glucose transporter 2 mRNA and protein expression, especially in the HFS group. Mothers' high-fat diet appears to intensify the stress response by changing the programming of the neuroendocrine system in the offspring.

  19. Gender comparison of psychophysical forces, cardiopulmonary, and muscle metabolic responses during a simulated cart pushing task.

    Maikala, Rammohan V; Ciriello, Vincent M; Dempsey, Patrick G; O'Brien, Niall V

    2010-10-01

    The purpose was to compare psychophysiological responses between healthy male and female workers during dynamic pushing. Using a psychophysical approach, 27 participants chose an acceptable force that they could push over a 7.6m distance at a frequency of 1 push per min on a treadmill. On a separate day, cardiopulmonary (e.g., whole-body oxygen uptake, heart rate, ventilation volume) and muscle metabolic measurements (change in muscle blood volume [ΔtHb] and Tissue Oxygenation Index [TOI]) from the right and left gastrocnemius muscles were collected simultaneously while participants pushed the previously chosen acceptable force on the treadmill at a similar frequency and distance for 2h. Results showed no significant difference between men and women for integrated force exerted on the instrumented treadmill handle and cardiopulmonary responses. In contrast, women demonstrated 45.7% lower ΔtHb but 3.6% higher TOI in the gastrocnemius region as compared to men, suggesting a lower hemoglobin concentration in women and high venous oxygen saturation during pushing. When ΔtHb and TOI were corrected for both body mass and pushing force, the disparity in gender was retained, implying an increased muscle oxygen saturation per force development in women than men during pushing. In the left gastrocnemius region, ΔtHb was 60% lower and TOI was 5.7% higher in women than men, suggesting an uneven muscle loading during pushing. Overall, the gender similarity in cardiopulmonary responses versus disparity in muscle metabolic responses suggest the importance of evaluating human performance during physical work at both whole-body and localized muscle levels. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

    Cassandra Collins

    2017-09-01

    Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  1. The effect of 8-week low impact aerobic exercise on plasma fibrinogen concentration in old women

    Shahla Dehghan

    2013-09-01

    Full Text Available Applied Exercise Physiology focuses on the physiological effects of exercise training on physiological processes, health, and physical well-being. The aim of this study was investigation of effects of 8-week low impact aerobic exercise on plasma fibrinogen concentration in old women. Fibrinogen is one of the most important inflammation factors and a prediction index in cardio vascular diseases. Iranian women especially older ones are generally sedentary because of their traditional and religious believes. Samples were 23 healthy and enable to do physical activity old women of Shahrekord (Chaharmahal va bakhtiary province, Iran retirement home. Subjects were randomly divided to two groups including experimental (n=14 individuals and control (n=11 individuals. First, for assessment of fibrinogen level, 5cc blood samples were obtained after 8 hours nightly fasting from anterior vein in resting condition. Experimental group was participated in 8 week (three times a week LIA training program (15 min in first day with 40% of maximum heart rate until 40 min in last day with 65% of maximum heart rate. All of mentioned measurements repeated at the end of 8 week training. The obtained results showed that 8 week LIA program has significant effect on reduction of old women plasma fibrinogen level (P=0.02. It seems that use of 8 week LIA training has positive effects on improvement of cardiovascular health and prevention of inflammation disease related to plasma fibrinogen level in Iranian old women. Key words: aerobic exercises, old women, fibrinogen.

  2. BOVINE PLASMA FIBRINOGEN AS MARKER IN CLINICAL AND SUB-CLINICAL MASTITIS

    R. Ali

    2018-06-01

    Full Text Available Plasma samples were collected from healthy as well as clinical and sub-clinical mastitis affected cows from Barasat, West Bengal, India. Plasma samples, after ammonium sulphate precipitation, were dialyzed against several changes of PBS (pH 7.2 to remove the excess ammonium sulphate. Then plasma fibrinogens were purified by gel filtration chromatography on Sephacryl S-200 HR. SDS-PAGE (10% of purified fibrinogen from plasma of healthy cow revealed polypeptide bands of 74, 67 and 57 kDa which represent the α (alpha, β (beta and γ (gamma- chains respectively. On the other hand, purified fibrinogen from plasma of sub-clinical and clinical mastitis affected cow revealed polypeptide bands of 73 (α-chain, 68 kDa (β-chain and 72 (γ-chain, 68 kDa (β-chain respectively. The SDS-PAGE analysis showed the absence of gamma (γ- chain of fibrinogen in both the samples of sub-clinical and clinical mastitis positive cow. Single precipitin line was observed in double immunodiffusion test when purified fibrinogen from healthy, clinical and subclinical mastitis positive cows reacted with hyper immune sera raised in rabbit. No precipitin line was found against the normal control serum. These purified fibrinogens also showed cross reactivity against antibody raised in rabbit when analyzed by western blot technique.

  3. Pre-delivery fibrinogen predicts adverse maternal or neonatal outcomes in patients with placental abruption.

    Wang, Liangcheng; Matsunaga, Shigetaka; Mikami, Yukiko; Takai, Yasushi; Terui, Katsuo; Seki, Hiroyuki

    2016-07-01

    Placental abruption is a severe obstetric complication of pregnancy that can cause disseminated intravascular coagulation and progress to massive post-partum hemorrhage. Coagulation disorder due to extreme consumption of fibrinogen is considered the main pathogenesis of disseminated intravascular coagulation in patients with placental abruption. The present study sought to determine if the pre-delivery fibrinogen level could predict adverse maternal or neonatal outcomes in patients with placental abruption. This retrospective medical chart review was conducted in a center for maternal, fetal, and neonatal medicine in Japan with 61 patients with placental abruption. Fibrinogen levels prior to delivery were collected and evaluated for the prediction of maternal and neonatal outcomes. The main outcome measures for maternal outcomes were disseminated intravascular coagulation and hemorrhage, and the main outcome measures for neonatal outcomes were Apgar score at 5 min, umbilical artery pH, and stillbirth. The receiver-operator curve and multivariate logistic regression analyses indicated that fibrinogen significantly predicted overt disseminated intravascular coagulation and the requirement of ≥6 red blood cell units, ≥10 fresh frozen plasma units, and ≥20 fresh frozen plasma units for transfusion. Moderate hemorrhage occurred in 71.5% of patients with a decrease in fibrinogen levels to 155 mg/dL. Fibrinogen could also predict neonatal outcomes. Umbilical artery pH neonatal outcomes with placental abruption. © 2016 Japan Society of Obstetrics and Gynecology. © 2016 Japan Society of Obstetrics and Gynecology.

  4. Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

    Ehling Rainer

    2011-10-01

    Full Text Available Abstract Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF of acute and chronic central (CNS and peripheral nervous system (PNS diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS, acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM and PNS (Guillain-Barré syndrome; GBS, as well as in non-inflammatory neurological controls (OND in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.

  5. Reaction of plasmic degradation products of fibrinogen in the radioimmunoassay of human fibrinopeptide A

    Budzynski, A.Z.; Marder, V.J.; Sherry, S.

    1975-01-01

    A radioimmunoassay (RIA) technique has been devised for the measurement of human fibrinopeptide A (FPA). The system utilizes rabbit antiserum to native human FPA and a synthetic fibrinopeptide, with tyrosine substituted for phenylanine in amino acid position 8. The test detects native human FPA at a concentration of 0.1 ng/ml, but does not cross react with human fibrinopeptide B or with fibrinopeptides A from canine, porcine, or bovine fibrinogen. Fibrinogen and chemical or plasmic degradation products with 2 moles of FPA per mole react fully in this test system. This includes the large-molecular-weight intermediate fragments X and Y and the NH 2 -terminal disulfide knot, and indicates that this antibody recognizes and reacts with FPA in the presence of the contiguous peptide structures presents in fibrinogen. Fragment E, which is derived from the NH 2 -terminal portion of fibrinogen, loses most of its FPA content after its liberation from its precursor derivative and reacts to a lesser extent in the RIA than do fragments X and Y. This correlates with the recovery of FPA-positive material from ultrafiltrates of extensive but not partial plasmic digests of fibrinogen. Although FPA immunoreactivity liberated from fibrinogen does not necessarily reflect thrombin activity and/or fibrin formation, only extensive plasmic degradation yields peptide material which reacts in this RIA system. This should not be a serious limitation to the application of the RIA in the detection of venous thrombosis. (U.S.)

  6. Fibrinogen plasma concentration is an independent marker of haemodynamic impairment in chronic thromboembolic pulmonary hypertension

    Hennigs, Jan K.; Baumann, Hans Jörg; Lüneburg, Nicole; Quast, Gesine; Harbaum, Lars; Heyckendorf, Jan; Sydow, Karsten; Schulte-Hubbert, Bernhard; Halank, Michael; Klose, Hans

    2014-01-01

    Fibrinogen has a crucial role in both inflammation and coagulation, two processes pivotal for the pathogenesis of pulmonary hypertension. We therefore aimed to investigate whether fibrinogen plasma concentrations a) are elevated in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and b) may serve as a novel biomarker for haemodynamic impairment. In a dual-centre, retrospective analysis including 112 patients with PAH (n = 52), CTEPH (n = 49) and a control cohort of patients with suspected PAH ruled out by right heart catheterisation (n = 11), we found fibrinogen plasma concentrations to be increased in patients with PAH (4.1 ± 1.4 g/l) and CTEPH (4.3 ± 1.2 g/l) compared to control patients (3.4 ± 0.5 g/l, p = 0.0035 and p = 0.0004, respectively). In CTEPH patients but not in PAH patients fibrinogen was associated with haemodynamics (p < 0.036) and functional parameters (p < 0.041). Furthermore, fibrinogen was linked to disease severity (WHO functional class, p = 0.017) and independently predicted haemodynamic impairment specifically in CTEPH (p < 0.016). Therefore, fibrinogen seems to represent an important factor in CTEPH pathophysiology and may have the potential to guide clinical diagnosis and therapy. PMID:24770447

  7. Evaluation of fibrinogen-DTPA-99mTc. Biodistribution and imaging studies

    Lungu, V.; Mihailescu, G.; Fugaru, V.; Preda, A.

    1998-01-01

    Labelling with 99m Tc of fibrinogen, using DTPA anhydride as the bifunctional chelating agent, was studied in animals with venous thrombi. The parameters studied were: i) coupled reaction of 99m Tc with the fibrinogen-DTPA-Sn(II) in lyophilised form; ii) biodistribution studies of fibrinogen- 99m Tc in animals with venous thrombi, and iii) imaging studies by scintigraphic methods. The present study showed that the radiochemical purity of fibrinogen-DTPA- 99m Tc is > 95% for a maximum of 5 mCi (185 MBq) radioactivity of 99m Tc in the 1.5-2 ml volume. Above this level of radioactivity we found a drastic decrease in the radiochemical purity. The radioactivity ratio of the venous thrombi to the blood was 2.32+-0.45. The scintigraphic images showed a significant accumulation of fibrinogen-DTPA- 99m Tc in 1-hour-old thrombi, 1 hour after injection. From this results the diagnostic potential of fibrinogen-DTPA-Sn(II) in kit form was evaluated. (author)

  8. Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

    Ji Soo Choi

    Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

  9. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

    2014-01-01

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  10. Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

    Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

    2014-09-15

    Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

  11. SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

    Campos, D; Peeters, W; Nickel, K; Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M

    2015-01-01

    Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response

  12. SU-C-303-02: Correlating Metabolic Response to Radiation Therapy with HIF-1alpha Expression

    Campos, D [University of Wisconsin Madison, Madison, WI (United States); Peeters, W [Radboud University Medical Center, Nijmegen, GA (United States); Nickel, K [University of Wisconsin, Madison, WI (United States); Eliceiri, K; Kimple, R; Van Der Kogel, A; Kissick, M [University of Wisconsin, Madison, Wisconsin (United States)

    2015-06-15

    Purpose: To understand radiation induced alterations in cellular metabolism which could be used to assess treatment or normal tissue response to aid in patient-specific adaptive radiotherapy. This work aims to compare the metabolic response of two head and neck cell lines, one malignant (UM-SCC-22B) and one benign (Normal Oral Keratinocyte), to ionizing radiation. Responses are compared to alterations in HIF-1alpha expression. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Measurements of metabolism and HIF-1alpha expression were taken before and X minutes after a 10 Gy dose of radiation delivered via an orthovoltage x-ray source. In vitro changes in metabolic activity were measured via fluorescence lifetime imaging (FLIM) to assess the mean lifetime of NADH autofluorescence following a dose of 10 Gy. HIF-1alpha expression was measured via immunohistochemical staining of in vitro treated cells and expression was quantified using the FIJI software package. Results: FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways for malignant cells; whereas this benign cell line showed little change in metabolic signature. Immunohistochemical analysis showed significant changes in HIF-1alpha expression in response to 10 Gy of radiation that correlate to metabolic profiles. Conclusion: Radiation induces significant changes in metabolic activity and HIF-1alpha expression. These alterations occur on time scales approximating the duration of common radiation treatments (approximately tens of minutes). Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response.

  13. Responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes: a randomized trial.

    Susan J van Dijk

    Full Text Available The ability of subjects to respond to nutritional challenges can reflect the flexibility of their biological system. Nutritional challenge tests could be used as an indicator of health status but more knowledge on metabolic and immune responses of different subjects to nutritional challenges is needed. The aim of this study was to compare the responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes.In a cross-over design 42 men (age 50-70 y consumed three high-fat shakes containing saturated fat (SFA, monounsaturated fat (MUFA or n-3 polyunsaturated (PUFA. Men were selected on BMI and health status (lean, obese or obese diabetic and phenotyped with MRI for adipose tissue distribution. Before and 2 and 4 h after shake consumption blood was drawn for measurement of expression of metabolic and inflammation-related genes in peripheral blood mononuclear cells (PBMCs, plasma triglycerides (TAG, glucose, insulin, cytokines and ex vivo PBMC immune response capacity. The MUFA and n-3 PUFA challenge, compared to the SFA challenge, induced higher changes in expression of inflammation genes MCP1 and IL1β in PBMCs. Obese and obese diabetic subjects had different PBMC gene expression and metabolic responses to high-fat challenges compared to lean subjects. The MUFA challenge induced the most pronounced TAG response, mainly in obese and obese diabetic subjects.The PBMC gene expression response and metabolic response to high-fat challenges were affected by fat type and metabolic risk phenotype. Based on our results we suggest using a MUFA challenge to reveal differences in response capacity of subjects.ClinicalTrials.gov NCT00977262.

  14. Proprietary tomato extract improves metabolic response to high-fat meal in healthy normal weight subjects

    Xavier Deplanque

    2016-10-01

    Full Text Available Background: Low-density lipoprotein (LDL oxidation is a risk factor for atherosclerosis. Lycopene and tomato-based products have been described as potent inhibitors of LDL oxidation. Objectives: To evaluate the effect of a 2-week supplementation with a carotenoid-rich tomato extract (CRTE standardized for a 1:1 ratio of lycopene and phytosterols, on post-prandial LDL oxidation after a high-fat meal. Design: In a randomized, double-blind, parallel-groups, placebo-controlled study, 146 healthy normal weight individuals were randomly assigned to a daily dose of CRTE standardized for tomato phytonutrients or placebo during 2 weeks. Oxidized LDL (OxLDL, glucose, insulin, and triglyceride (TG responses were measured for 8 h after ingestion of a high-fat meal before and at the end of intervention. Results: Plasma lycopene, phytofluene, and phytoene were increased throughout the study period in the CRTE group compared to placebo. CRTE ingestion significantly improved changes in OxLDL response to high-fat meal compared to placebo after 2 weeks (p<0.0001. Changes observed in glucose, insulin, and TG responses were not statistically significant after 2 weeks of supplementation, although together they may suggest a trend of favorable effect on metabolic outcomes after a high-fat meal. Conclusions: Two-week supplementation with CRTE increased carotenoids levels in plasma and improved oxidized LDL response to a high-fat meal in healthy normal weight individuals.

  15. Modification of nucleotide metabolism in relationship with differentiation and in response to irradiation in human tumour cells

    Wei, Shuang

    1998-01-01

    This research thesis reports the study of the metabolism of nucleotides in human tumour cells. The first part addresses the modifications of nucleotide (more specifically purine) metabolism in relationship with human melanoma cell proliferation and differentiation. The second part addresses the modifications of this metabolism in response to an irradiation in human colon tumour cells. For each part, the author proposes a bibliographic synthesis, and a presentation of studied cells and of methods used to grow cells, and respectively to proliferate and differentiate them or to irradiate them, and then discusses the obtained results [fr

  16. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

    Fenja Klevenhusen

    2015-10-01

    Full Text Available Left displaced abomasum (LDA is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1 evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2 establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca, but greater concentrations of non-esterified fatty acids (NEFA and beta-hydroxy-butyrate (BHBA, in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA, regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA.

  17. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions.

    Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

    2015-10-13

    Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA.

  18. Energy metabolism and metabolomics response of Pacific white shrimp Litopenaeus vannamei to sulfide toxicity.

    Li, Tongyu; Li, Erchao; Suo, Yantong; Xu, Zhixin; Jia, Yongyi; Qin, Jian G; Chen, Liqiao; Gu, Zhimin

    2017-02-01

    The toxicity and poisoning mechanisms of sulfide were studied in Litopenaeus vannamei from the perspective of energy metabolism and metabolomics. The lethal concentrations of sulfide in L. vannamei (LC50) at 24h, 48h, 72h, and 96h were determined. Sulfide at a concentration of 0, 1/10 (425.5μg/L), and 1/5 (851μg/L) of the LC 50 at 96h was used to test the metabolic responses of L. vannamei for 21days. The chronic exposure of shrimp to a higher sulfide concentration of 851μg/L decreased shrimp survival but did not affect weight gain or the hepatopancreas index. The glycogen content in the hepatopancreas and muscle and the activity of hepatopancreas cytochrome C oxidase of the shrimp exposed to all sulfide concentrations were significantly lower, and the serum glucose and lactic acid levels and lactic acid dehydrogenase activity were significantly lower than those in the control. Metabolomics assays showed that shrimp exposed to sulfide had lower amounts of serum pyruvic acid, succinic acid, glycine, alanine, and proline in the 425.5μg/L group and phosphate, succinic acid, beta-alanine, serine, and l-histidine in the 851μg/L group than in the control. Chronic sulfide exposure could disturb protein synthesis in shrimp but enhance gluconeogenesis and substrate absorption for ATP synthesis and tricarboxylic acid cycles to provide extra energy to cope with sulfide stress. Chronic sulfide exposure could adversely affect the health status of L. vannamei, as indicated by the high amounts of serum n-ethylmaleamic acid, pyroglutamic acid, aspartic acid and phenylalanine relative to the control. This study indicates that chronic exposure of shrimp to sulfide can decrease health and lower survival through functional changes in gluconeogenesis, protein synthesis and energy metabolism. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Assessment of chitosan-affected metabolic response by peroxisome proliferator-activated receptor bioluminescent imaging-guided transcriptomic analysis.

    Chia-Hung Kao

    Full Text Available Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR, a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo.

  20. Muscle Damage and Metabolic Responses to Repeated-Sprint Running With and Without Deceleration.

    Minahan, Clare L; Poke, Daniel P; Morrison, Jaime; Bellinger, Phillip M

    2018-04-04

    Minahan, CL, Poke, DP, Morrison, J, and Bellinger, PM. Muscle damage and metabolic responses to repeated-sprint running with and without deceleration. J Strength Cond Res XX(X): 000-000, 2017-This study aimed to determine whether repeated-sprint running with deceleration aggravates markers of muscle damage or delays the recovery of performance compared with repeated-sprint running without deceleration. Fourteen male team-sport athletes performed 2 randomly ordered testing sessions on a nonmotorized treadmill with one session requiring participants to decelerate (TMd) within 4 seconds before stopping or immediately step to the side of the treadmill belt at the completion of each sprint (TMa). Peak and mean velocities, speed decrement, blood lactate concentrations, and oxygen uptake were monitored during the repeated-sprint running protocols. Countermovement vertical jump (CMJ) performance, perceived muscle soreness, sit-and-reach flexibility, plasma creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb) concentrations were quantified immediately before and after and 45 minutes, 24 and 48 hours after repeated-sprint running protocols. Although muscle damage was indicated by increases in CK, LDH, and Mb (p ≤ 0.05) in both groups, there was no significant effect of condition (TMa vs. TMd) on any of the measured performance or physiological variables (p > 0.05). The present study indicated that the removal of deceleration from repeated-sprint running on a nonmotorized treadmill has no effect on metabolism or performance during or after repeated-sprint running or markers of muscle damage.

  1. Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

    Zhen Li

    2017-10-01

    Full Text Available Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6, metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production.

  2. Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows.

    Esposito, Giulia; Irons, Pete C; Webb, Edward C; Chapwanya, Aspinas

    2014-01-30

    The biological cycles of milk production and reproduction determine dairying profitability thus making management decisions dynamic and time-dependent. Diseases also negatively impact on net earnings of a dairy enterprise. Transition cows in particular face the challenge of negative energy balance (NEB) and/or disproportional energy metabolism (fatty liver, ketosis, subacute, acute ruminal acidosis); disturbed mineral utilization (milk fever, sub-clinical hypocalcemia); and perturbed immune function (retained placenta, metritis, mastitis). Consequently NEB and reduced dry matter intake are aggravated. The combined effects of all these challenges are reduced fertility and milk production resulting in diminishing profits. Risk factors such as NEB, inflammation and impairment of the immune response are highly cause-and-effect related. Thus, managing cows during the transition period should be geared toward reducing NEB or feeding specially formulated diets to improve immunity. Given that all cows experience a reduced feed intake and body condition, infection and inflammation of the uterus after calving, there is a need for further research on the immunology of transition dairy cows. Integrative approaches at the molecular, cellular and animal level may unravel the complex interactions between disturbed metabolism and immune function that predispose cows to periparturient diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

    Li, Zhen; Liu, Jian-Zhong

    2017-01-01

    Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic analysis was carried out. Overproduction of putrescine resulted in transcriptional downregulation of genes involved in glycolysis; the TCA cycle, pyruvate degradation, biosynthesis of some amino acids, oxidative phosphorylation; vitamin biosynthesis (thiamine and vitamin 6), metabolism of purine, pyrimidine and sulfur, and ATP-, NAD-, and NADPH-consuming enzymes. The transcriptional levels of genes involved in ornithine biosynthesis and NADPH-forming related enzymes were significantly upregulated in the putrescine producing C. glutamicum strain PUT-ALE. Comparative transcriptomic analysis provided some genetic modification strategies to further improve putrescine production. Repressing ATP- and NADPH-consuming enzyme coding gene expression via CRISPRi enhanced putrescine production. PMID:29089930

  4. Metabolic and cardiorespiratory response in swimmers during head-out immersion: a prospective study.

    Mesfar, Mohamed A; Zendah, Ines; Gharsalli, Houda; Ben Hassen, Chokri; Ghedira, Habib

    2012-11-01

    Sport represents a stress for the body. Many metabolic and cardiorespiratory changes are known during physical activity.However, litte is known in swimmers particularly during head-out immersion. To determine the metabolic and cardiorespiratory response in swimmers during head-out immersion. The energetic, cardiovascular function and ventilatory requirements of a 10 min steady state arm exercise performed by 13 healthy subjects in air and during immersion up to the hip in 26°C water were compared. The same ergometric work load was achieved with an average maximum oxygen uptake of 3.9 ± 2.63 l/min in air versus 3.55 ± 2.48 l/min in water (p=0.953). During exercise, the average values of minute ventilation, ventilation equivalent for oxygen, ventilation equivalent for CO2, peak expiratory flow, respiratory exchange ratio and heart rate were not different in water and in air. However, first ventilatory threshold was significantly higher in water than in air. The mean value of the first ventilatory threshold was 0.89 ± 0.23 l/min in air, and 1.08 ± 0.23 l/min in water immersion; (p=0.016). These results suggest that training swimmers favoring immersion (weight belts) may improve their aerobic capacity.

  5. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer

    John Wikswo

    2009-03-01

    Full Text Available Harnessing the potential of cells as complex biosensors promises the potential to create sensitive and selective detectors for discrimination of biodefense agents. Here we present toxin detection and suggest discrimination using cells in a multianalyte microphysiometer (MMP that is capable of simultaneously measuring flux changes in four extracellular analytes (acidification rate, glucose uptake, oxygen uptake, and lactate production in real-time. Differential short-term cellular responses were observed between botulinum neurotoxin A and ricin toxin with neuroblastoma cells, alamethicin and anthrax protective antigen with RAW macrophages, and cholera toxin, muscarine, 2,4-dinitro-phenol, and NaF with CHO cells. These results and the post exposure dynamics and metabolic recovery observed in each case suggest the usefulness of cell-based detectors to discriminate between specific analytes and classes of compounds in a complex matrix, and furthermore to make metabolic inferences on the cellular effects of the agents. This may be particularly valuable for classifying unknown toxins.

  6. Metabolic responses to sulfur dioxide in grapevine (Vitis vinifera L.: photosynthetic tissues and berries

    Michael James Considine

    2015-02-01

    Full Text Available Research on sulfite metabolism in plants has historically been undertaken within the context of industrial pollution. Resolution of the problem of sulfur pollution has led to sulfur deficiency in many soils and questions remain concerning how different plant organs deal with reactive and potentially toxic sulfur metabolites. In this review, we discuss sulfur dioxide/ sulfite assimilation in grape berries in relation to gene expression and quality traits, features that remain significant to the food industry. We consider the intrinsic metabolism of sulfite and its consequences for fruit biology and postharvest physiology, comparing the different responses in fruit and leaves. We also highlight inconsistencies in what is considered the ‘ambient’ environmental or industrial exposures to SO2. We discuss these findings in relation to the persistent threat to the table grape industry that intergovernmental agencies will revoke the industry’s exemption to the worldwide ban on the use of SO2 for preservation of fresh foods. Transcriptome profiling studies on fruit suggest that added value may accrue from effects of SO2 fumigation on the expression of genes encoding components involved in processes that underpin traits related to customer satisfaction, particularly in table grapes, where SO¬2 fumigation may extend for several months.

  7. Metabolic responses to sulfur dioxide in grapevine (Vitis vinifera L.): photosynthetic tissues and berries.

    Considine, Michael J; Foyer, Christine H

    2015-01-01

    Research on sulfur metabolism in plants has historically been undertaken within the context of industrial pollution. Resolution of the problem of sulfur pollution has led to sulfur deficiency in many soils. Key questions remain concerning how different plant organs deal with reactive and potentially toxic sulfur metabolites. In this review, we discuss sulfur dioxide/sulfite assimilation in grape berries in relation to gene expression and quality traits, features that remain significant to the food industry. We consider the intrinsic metabolism of sulfite and its consequences for fruit biology and postharvest physiology, comparing the different responses in fruit and leaves. We also highlight inconsistencies in what is considered the "ambient" environmental or industrial exposures to SO2. We discuss these findings in relation to the persistent threat to the table grape industry that intergovernmental agencies will revoke the industry's exemption to the worldwide ban on the use of SO2 for preservation of fresh foods. Transcriptome profiling studies on fruit suggest that added value may accrue from effects of SO2 fumigation on the expression of genes encoding components involved in processes that underpin traits related to customer satisfaction, particularly in table grapes, where SO2 fumigation may extend for several months.

  8. Food odors trigger an endocrine response that affects food ingestion and metabolism.

    Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

    2015-08-01

    Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling.

  9. Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction. The ECTIM Study. Etude Cas-Temoins sur l'Infarctus du Myocarde.

    Behague, I; Poirier, O; Nicaud, V; Evans, A; Arveiler, D; Luc, G; Cambou, J P; Scarabin, P Y; Bara, L; Green, F; Cambien, F

    1996-02-01

    Polymorphisms of the beta fibrinogen gene have been shown to affect plasma fibrinogen levels and the risk of peripheral arterial disease. We now present the results of a detailed analysis of the beta fibrinogen gene in relation to plasma fibrinogen and to the severity of coronary artery disease (CAD) in patients with myocardial infarction (MI) in the ECTIM Study. Ten polymorphisms of the beta fibrinogen gene, including five new polymorphisms identified by single-strand conformation polymorphism analysis, and one polymorphism in the 3' flanking region of the alpha fibrinogen gene were investigated in 565 patients with MI and 668 control subjects. The polymorphisms were in tight linkage disequilibrium and the genotype frequencies were similar in patients with MI and control subjects. In the multivariate analysis, only two polymorphisms, beta Hae III (P 50% stenosis was estimated by angiography and used as a criterion for severity of CAD. Presence of the less frequent allele of the beta Bcl I (P < .0003) and of other polymorphisms was positively associated with the severity of CAD. Genetic variants of the beta fibrinogen gene are associated with an increased plasma level of fibrinogen, especially in smokers. The association with CAD appears to be the consequence of an increased risk of MI in subjects with severe CAD who carry the predisposing beta fibrinogen genotypes.

  10. Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing.

    Zuliani-Alvarez, Lorena; Midwood, Kim S

    2015-05-01

    Significance: Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. Recent Advances: An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Critical Issues: Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Future Directions: Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing.

  11. Metabolic response of Danaüs archippus and Saccharomyces cerevisiae to weak oscillatory magnetic fields

    Russell, D. N.; Webb, S. J.

    1981-09-01

    Respiration of the insect larva, Danaüs archippus, and the yeast, Saccharomyces cerevisiae, in log phase has been monitored before and after an oscillatory magnetic insult of 0.005 Gauss rms amplitude and 40 50 min duration. Frequencies used were 10 16 Hz for the insect and 100 200 Hz for the yeast. Depression of as much as 30% in metabolic rate has been found to occur immediately after the field is both imposed and eliminated with a general recovery over the 30-min period thereafter both in and out of the imposed field, although complete recovery to original levels may take much longer. Evidence is given that the response may depend on the frequency pattern used. This data is used to formulate an hypothesis whereby changes in the geomagnetic field variability pattern may act as a biochronometric zeitgeber.

  12. Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

    Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M; Clements, Austin; Harmata, Emily E; Marks-Shulman, Pam; Gaylinn, Bruce D; Williams, Brandon; Clements, Ronald H; Albaugh, Vance L; Abumrad, Naji N

    2017-09-01

    Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg -1  min -1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB. © 2017 John Wiley & Sons Ltd.

  13. Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study.

    De Pietri, Lesley; Ragusa, Francesca; Deleuterio, Annalisa; Begliomini, Bruno; Serra, Valentina

    2016-01-01

    Patients undergoing orthotopic liver transplantation are at high risk of bleeding complications. Several Authors have shown that thromboelastography (TEG)-based coagulation management and the administration of fibrinogen concentrate reduce the need for blood transfusion. We conducted a single-center, retrospective cohort observational study (Modena Polyclinic, Italy) on 386 consecutive patients undergoing liver transplantation. We assessed the impact on resource consumption and patient survival after the introduction of a new TEG-based transfusion algorithm, requiring also the introduction of the fibrinogen functional thromboelastography test and a maximum amplitude of functional fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based algorithm previously used (2005-2011, n = 268). After 2012, there was a significant decrease in the use of homologous blood (1502 ± 1376 vs 794 ± 717 mL, P < 0.001), fresh frozen plasma (537 ± 798 vs 98 ± 375 mL, P < 0.001), and platelets (158 ± 280 vs 75 ± 148 mL, P < 0.005), whereas the use of fibrinogen increased (0.1 ± 0.5 vs 1.4 ± 1.8 g, P < 0.001). There were no significant differences in 30-day and 6-month survival between the 2 groups. The implementation of a new coagulation management method featuring the addition of the fibrinogen functional thromboelastography test to the TEG test according to an algorithm which provides for the administration of fibrinogen has helped in reducing the need for transfusion in patients undergoing liver transplantation with no impact on their survival.

  14. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  15. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

  16. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

    2010-01-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  17. Fagus sylvatica L. provenances maintain different leaf metabolic profiles and functional response

    Aranda, Ismael; Sánchez-Gómez, David; de Miguel, Marina; Mancha, Jose Antonio; Guevara, María Angeles; Cadahía, Estrella; Fernández de Simón, María Brígida

    2017-07-01

    Most temperate forest tree species will suffer important environmental changes as result of the climate change. Adaptiveness to local conditions could change at different sites in the future. In this context, the study of intra-specific variability is important to clarify the singularity of different local populations. Phenotypic differentiation between three beech provenances covering a wide latitudinal range (Spain/ES, Germany/DE and Sweden/SE), was studied in a greenhouse experiment. Non-target leaf metabolite profiles and ecophysiological response was analyzed in well-watered and water stressed seedlings. There was a provenance-specific pattern in the relative concentrations of some leaf metabolites regardless watering treatment. The DE and SE from the center and north of the distribution area of the species showed a clear differentiation from the ES provenance in the relative concentration of some metabolites. Thus the ES provenance from the south maintained larger relative concentration of some organic and amino acids (e.g. fumaric and succinic acids or valine and isoleucine), and in some secondary metabolites (e.g. kaempferol, caffeic and ferulic acids). The ecophysiological response to mild water stress was similar among the three provenances as a consequence of the moderate water stress applied to seedlings, although leaf N isotope composition (δ15N) and leaf C:N ratio were higher and lower respectively in DE than in the other two provenances. This would suggest potential differences in the capacity to uptake and post-process nitrogen according to provenance. An important focus of the study was to address for the first time inter-provenance leaf metabolic diversity in beech from a non-targeted metabolic profiling approach that allowed differentiation of the three studied provenances.

  18. Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

    Fumiaki Obata

    2014-05-01

    Full Text Available Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM levels due to glycine N-methyltransferase (Gnmt upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.

  19. Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia.

    Jackson, Kim G; Walden, Charlotte M; Murray, Peter; Smith, Adrian M; Minihane, Anne M; Lovegrove, Julie A; Williams, Christine M

    2013-08-01

    Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. MetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (Pcurve (AUC) and incremental AUC (P ≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (Pglucose to be an important predictor of the postprandial TAG and glucose response. Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. The Metabolic Response to Stress and Infection in Critically Ill Children: The Opportunity of an Individualized Approach

    Valentina De Cosmi

    2017-09-01

    Full Text Available The metabolic response to stress and infection is closely related to the corresponding requirements of energy and nutrients. On a general level, the response is driven by a complex endocrine network and related to the nature and severity of the insult. On an individual level, the effects of nutritional interventions are highly variable and a possible source of complications. This narrative review aims to discuss the metabolic changes in critically-ill children and the potential of developing personalized nutritional interventions. Through a literature search strategy, we have investigated the importance of blood glucose levels, the nutritional aspects of the different phases of acute stress response, and the reliability of the available tools to assess the energy expenditure. The dynamics of metabolism during stressful events reveals the difficult balance between risk of hypo- or hyperglycemia and under- or overfeeding. Within this context, individualized and accurate measurement of energy expenditure may help in defining the metabolic needs of patients. Given the variability of the metabolic response in critical conditions, randomized clinical studies in ill children are needed to evaluate the effect of individualized nutritional intervention on health outcomes.

  1. Maximal exercise electrocardiographic responses and coronary heart disease mortality among men with metabolic syndrome.

    Lyerly, G William; Sui, Xuemei; Church, Timothy S; Lavie, Carl J; Hand, Gregory A; Blair, Steven N

    2010-03-01

    To examine the association between abnormal exercise electrocardiographic (E-ECG) test results and mortality (all-cause and that resulting from coronary heart disease [CHD] or cardiovascular disease [CVD]) in a large population of asymptomatic men with metabolic syndrome (MetS). A total of 9191 men (mean age, 46.9 years) met the criteria of having MetS. All completed a maximal E-ECG treadmill test (May 14, 1979, through April 9, 2001) and were without a previous CVD event or diabetes at baseline. Main outcomes were all-cause mortality, mortality due to CHD, and mortality due to CVD. Cox regression analysis was used to quantify the mortality risk according to E-ECG responses. During a follow-up of 14 years, 633 deaths (242 CVD and 150 CHD) were identified. Mortality rates and hazard ratios (HRs) across E-ECG responses were the following: for all-cause mortality: HR, 1.36; 95% confidence interval (CI), 1.09-1.70 for equivocal responses and HR, 1.41; 95% CI, 1.12-1.77 for abnormal responses (P(trend)<.001); for mortality due to CVD: HR, 1.29; 95% CI, 0.88-1.88 for equivocal responses and HR, 2.04; 95% CI, 1.46-2.84 for abnormal responses (P(trend)<.001); and for mortality due to CHD: HR, 1.62; 95% CI, 1.02-2.56 for equivocal responses and HR, 2.45; 95% CI, 1.62-3.69 for abnormal responses (P(trend)<.001). A positive gradient for CHD, CVD, and all-cause mortality rates across E-ECG categories within 3, 4, or 5 MetS components was observed (P<.001 for all). Among men with MetS, an abnormal E-ECG response was associated with higher risk of all-cause, CVD, and CHD mortality. These findings underscore the importance of E-ECG tests to identify men with MetS who are at risk of dying.

  2. Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations.

    Jmel, Haifa; Romdhane, Lilia; Ben Halima, Yosra; Hechmi, Meriem; Naouali, Chokri; Dallali, Hamza; Hamdi, Yosr; Shan, Jingxuan; Abid, Abdelmajid; Jamoussi, Henda; Trabelsi, Sameh; Chouchane, Lotfi; Luiselli, Donata; Abdelhak, Sonia; Kefi, Rym

    2018-01-01

    Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6.0 genotyping array. Variants located in 24 Very Important Pharmacogenes (VIP) involved in MetS drug response were extracted from the genotyping data. Analysis of variant distribution in Tunisian population compared to 20 worldwide populations publicly available was performed using R software packages. Common variants between Tunisians and the 20 investigated populations were extracted from genotyping data. Multidimensional screening showed that Tunisian population is clustered with North African and European populations. The greatest divergence was observed with the African and Asian population. In addition, we performed Inter-ethnic comparison based on the genotype frequencies of five VIP biomarkers. The genotype frequencies of the biomarkers rs3846662, rs1045642, rs7294 and rs12255372 located respectively in HMGCR, ABCB1, VKORC1 and TCF7L2 are similar between Tunisian, Tuscan (TSI) and European (CEU). The genotype frequency of the variant rs776746 located in CYP3A5 gene is similar between Tunisian and African populations and different from CEU and TSI. The present study shows that the genetic make up of the Tunisian population is relatively complex in regard to pharmacogenes and reflects previous historical events. It is important to consider this ethnic difference in drug prescription in order to optimize drug response to avoid serious adverse drug reactions. Taking into account similarities with

  3. Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations

    Jmel, Haifa; Romdhane, Lilia; Ben Halima, Yosra; Hechmi, Meriem; Naouali, Chokri; Dallali, Hamza; Hamdi, Yosr; Shan, Jingxuan; Abid, Abdelmajid; Jamoussi, Henda; Trabelsi, Sameh; Chouchane, Lotfi; Luiselli, Donata; Abdelhak, Sonia

    2018-01-01

    Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6.0 genotyping array. Variants located in 24 Very Important Pharmacogenes (VIP) involved in MetS drug response were extracted from the genotyping data. Analysis of variant distribution in Tunisian population compared to 20 worldwide populations publicly available was performed using R software packages. Common variants between Tunisians and the 20 investigated populations were extracted from genotyping data. Multidimensional screening showed that Tunisian population is clustered with North African and European populations. The greatest divergence was observed with the African and Asian population. In addition, we performed Inter-ethnic comparison based on the genotype frequencies of five VIP biomarkers. The genotype frequencies of the biomarkers rs3846662, rs1045642, rs7294 and rs12255372 located respectively in HMGCR, ABCB1, VKORC1 and TCF7L2 are similar between Tunisian, Tuscan (TSI) and European (CEU). The genotype frequency of the variant rs776746 located in CYP3A5 gene is similar between Tunisian and African populations and different from CEU and TSI. The present study shows that the genetic make up of the Tunisian population is relatively complex in regard to pharmacogenes and reflects previous historical events. It is important to consider this ethnic difference in drug prescription in order to optimize drug response to avoid serious adverse drug reactions. Taking into account similarities with

  4. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

  5. Comparison of standard fibrinogen measurement methods with fibrin clot firmness assessed by thromboelastometry in patients with cirrhosis.

    Vucelic, Dragica; Jesic, Rada; Jovicic, Snezana; Zivotic, Maja; Grubor, Nikica; Trajkovic, Goran; Canic, Ivana; Elezovic, Ivo; Antovic, Aleksandra

    2015-06-01

    The Clauss fibrinogen method and thrombin clotting time (TCT) are still routinely used in patients with cirrhosis to define fibrinogen concentration and clotting potential. The thromboelastometric functional fibrinogen FIBTEM assay evaluates the strength of fibrin-based clots in whole blood, providing information on both quantitative deficit and fibrin polymerization disorders. To compare these three methods of assessing fibrinogen in patients with cirrhosis of different aetiologies, characterized by impairment in fibrinogen concentration as well as functional aberrance. Sixty patients with alcoholic and 24 patients with cholestatic cirrhosis were included (Child-Pugh score (CPs)A, n=24; B, n=32; C, n=28). All parameters were compared with those from a control group. Maximum clot firmness (MCF) in the FIBTEM test was assessed in regard to its relevance in detection of qualitative fibrinogen disorders in comparison with results obtained by standard measurement methods, i.e. the Clauss fibrinogen method and TCT. With increased cirrhosis severity, fibrinogen and FIBTEM-MCF levels significantly declined (p=0.002), while TCT was significantly prolonged (p=0.002). In all CPs groups, fibrinogen strongly correlated with FIBTEM-MCF (r=0.77, r=0.72, r=0.74; pmeasurement in cirrhotic patients, especially in evaluating fibrin polymerization disorders in these patients. Further studies are needed to evaluate the usefulness of this assay in predicting bleeding complications in cirrhotic patients as well as monitoring replacement treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Stress hormone release is a key component of the metabolic response to lipopolysaccharide (LPS): studies in hypopituitary and healthy subjects

    Bach, Ermina; Møller, Andreas Buch; Jørgensen, Jens Otto Lunde

    2016-01-01

    OBJECTIVE: Lipopolysaccharide (LPS) generates acute and chronic inflammatory and metabolic responses during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but it is unclear whether these responses depend on intact pituitary release...... but not in HP. LPS increased whole body palmitate fluxes (3-fold) and decreased palmitate specific activity 40-50 % in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue mRNA was decreased in CTR. LPS increased phenylalanine fluxes significantly more in CTR, whereas...

  7. Physiological and Metabolic Changes of Purslane (Portulaca oleracea L.) in Response to Drought, Heat, and Combined Stresses

    Jin, Rui; Wang, Yanping; Liu, Ruijie; Gou, Junbo; Chan, Zhulong

    2016-01-01

    Purslane (Portulaca oleracea L.) is a fleshy herbaceous plant. So far, little information is available on the response of this plant to combined drought and heat stress. In this study, changes in physiological and metabolic levels were characterized after treatments with drought, heat and combined stresses. Both individual and combined stress treatments increased malondialdehyde (MDA), electrolyte leakage (EL), O2•− and activities of superoxide dismutase (SOD), peroxidase (POD), while declined chlorophyll content. No significant differences were found between control and treatments in leaf water content (LWC) and catalase (CAT) activity. Additionally, 37 metabolic compounds were detected in purslane. Through pathway analysis, 17 metabolites were directly involved in the glycolysis metabolic pathway. The present study indicated that combined drought and heat stress caused more serious damage in purslane than individual stress. To survive, purslane has a high capability to cope with environmental stress conditions through activation of physiological and metabolic pathways. PMID:26779204

  8. Physiological and metabolic changes of purslane (Portulaca oleracea L. in response to drought, heat and combined stresses

    Rui eJin

    2016-01-01

    Full Text Available Purslane (Portulaca oleracea L. is a fleshy herbaceous plant. So far, little information is available on the response of this plant to combined drought and heat stress. In this study, changes in physiological and metabolic levels were characterized after treatments with drought, heat and combined stresses. Both individual and combined stress treatments increased malondialdehyde (MDA, electrolyte leakage (EL, O2•− and activities of superoxide dismutase (SOD, peroxidase (POD, while declined chlorophyll content. No significant differences were found between control and treatments in leaf water content (LWC and catalase (CAT activity. Additionally, 37 metabolic compounds were detected in purslane. Through pathway analysis, 17 metabolites were directly involved in the glycolysis metabolic pathway. The present study indicated that combined drought and heat stress caused more serious damage in purslane than individual stress. To survive, purslane has a high capability to cope with environmental stress conditions through activation of physiological and metabolic pathways.

  9. Albumin and fibrinogen levels′ relation with orthopedics traumatic patients′ outcome after massive transfusion

    Mohammadreza Bazavar

    2014-01-01

    Full Text Available Background: Severe bleeding is common during limb trauma. It can lead to hemorrhagic shock required to massive blood transfusion. Coagulopathy is the major complication of massive transfusion-induced increased mortality rate. Aim of this study was evaluation of fibrinogen and albumin levels association with orthopedics traumatic patients′ outcome who received massive transfusion. Methods: In a cross sectional study, 23 patients with severe limb injury admitted to orthopedic emergency department were studied. All the patients received massive transfusion, that is, >10 unit blood. Albumin and fibrinogen levels are measured at admission and 24 h later, and compared according to final outcome. Results: Twenty-three traumatic patients with severe limb injuries were studied, out of which ten (43.2% died and 13 (56.8% were alive. There was significant difference between patients outcome in fibrinogen level after 24 h, but no difference was observed in albumin levels. Based on regression model, fibrinogen after 24 h had a significant role in determining the final outcome in traumatic patients who received massive transfusion (odds ratio 0.48, 95% confidence interval 0.15-0.92, P = 0.02. Conclusions: According to our results, fibrinogen level is the most important factor in determination of orthopedics traumatic patients when received massive transfusion. However, serum albumin does not play any role in patients′ outcome.

  10. Identification of fibrinogen-binding proteins of Aspergillus fumigatus using proteomic approach.

    Upadhyay, Santosh Kumar; Gautam, Poonam; Pandit, Hrishikesh; Singh, Yogendra; Basir, Seemi Farhat; Madan, Taruna

    2012-03-01

    Aspergillus fumigatus, the main etiological agent for various forms of human aspergillosis, gets access to the respiratory system of human host by inhalation of airborne conidia. These conidia possibly adhere to extracellular matrix (ECM) proteins. Among the ECM proteins involved in adherence, fibrinogen is thought to be crucial. Here, we studied whether A. fumigatus three-week culture filtrate (3wcf) proteins promote binding of A. fumigatus to ECM proteins and promote fungal growth. We observed that incubation of ECM with 3wcf proteins led to dose- and time-dependent increase in adherence of conidia to the ECM. In order to identify the catalogue of fibrinogen-binding A. fumigatus proteins, we carried out fibrinogen affinity blotting using two-dimensional gel electrophoresed 3wcf proteins. A total of 15 fibrinogen-binding protein spots corresponding to 7 unique proteins were identified in 3wcf using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF-TOF). Among these, 4 proteins, namely, beta-glucosidase, alpha-mannosidase, pectate lyase A and oryzin precursor were predicted to have cell wall or extracellular localization, whereas amidase family protein and two hypothetical proteins did not display the signal sequence. This study reports seven novel fibrinogen-binding proteins of A. fumigatus, some of which could be further explored for targeting the adhesion phenomenon as antifungal strategy.

  11. Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI.

    Nelson, Sarah J

    2011-07-01

    MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low-grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12-15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium-enhancing lesion on T(1) -weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T(2) lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti-angiogenic and anti

  12. Antarctic fish in a changing world: metabolic, osmoregulatory and endocrine stress response

    Pedro Miguel Guerreiro

    2015-10-01

    Full Text Available Fish around Antarctic Peninsula are exposed to the fastest climate change rate in the planet, up to ten times higher than the global average. The evolution in extreme stenothermal isolation was a strong selective pressure for the development of a highly endemic fish fauna, with likely structural and functional constraints. To which extent can coastal notothenioid fish adjust to the conditions forecasted by the models of climate change? Experiments were run in the Arctowski (PL station at Admiralty Bay, King George Island, in 2012/13. Fish, Notothenia rossii and N. coriiceps, were collected by boat at 5-25 meter deep using fishing poles and were transferred to experimental tanks in cold rooms acclimated to natural temperatures (0-2°C. Fish were exposed to rapid/ gradual changes in water temperature or/and salinity (to 6-8°C using thermostat-controlled heaters, to 20-10‰ by addition of freshwater to recirculating tanks, over a period of up to 10 days to evaluate the response of several physiological processes. The stress endocrine axis was tested by injecting known blockers/ agonists of cortisol release and receptors. Exposure to altered conditions had no effect in immediate mortality. Increased temperature reduced overall activity and behavioral response to stimuli, although it had no clear effect on mobilization of energetic substrate. Both cortisol and gene expression of metabolic-related proteins and glucocorticoid- and mineralocorticoid receptors were modified after heat shock, but that the cortisol response to handling was reduced. The rise in temperature induced a dependent decrease in plasma osmolality while increasing branchial Na+/K+-ATPase activity, thus decreasing osmoregulatory efficiency. In conclusion, Antarctic fish are reactive to environmental change, but that their ability to accommodate rapid or adaptive responses may be compromised.

  13. Insulin response of the glucose and fatty acid metabolism in dry dairy cows across a range of body condition scores.

    De Koster, J; Hostens, M; Van Eetvelde, M; Hermans, K; Moerman, S; Bogaert, H; Depreester, E; Van den Broeck, W; Opsomer, G

    2015-07-01

    The objective of the present research was to determine the insulin response of the glucose and fatty acid metabolism in dry dairy cows with a variable body condition score (BCS). Ten pregnant Holstein Friesian dairy cows (upcoming parity 2 to 5) were selected based on BCS at the beginning of the study (2mo before expected parturition date). During the study, animals were monitored weekly for BCS and backfat thickness and in the last 2wk, blood samples were taken for determination of serum nonesterified fatty acid (NEFA) concentration. Animals underwent a hyperinsulinemic euglycemic clamp test in the third week before the expected parturition date. The hyperinsulinemic euglycemic clamp test consisted of 4 consecutive insulin infusions with increasing insulin doses: 0.1, 0.5, 2, and 5mIU/kg per minute. For each insulin infusion period, a steady state was defined as a period of 30min where no or minor changes of the glucose infusion were necessary to keep the blood glucose concentration constant and near basal levels. During the steady state, the glucose infusion rate [steady state glucose infusion rate (SSGIR) in µmol/kg per minute] and NEFA concentration [steady state NEFA concentration (SSNEFA) in mmol/L] were determined and reflect the insulin response of the glucose and fatty acid metabolism. Dose response curves were created based on the insulin concentrations during the steady state and the SSGIR or SSNEFA. The shape of the dose response curves is determined by the concentration of insulin needed to elicit the half maximal effect (EC50) and the maximal SSGIR or the minimal SSNEFA for the glucose or fatty acid metabolism, respectively. The maximal SSGIR was negatively associated with variables reflecting adiposity of the cows (BCS, backfat thickness, NEFA concentration during the dry period, and absolute weight of the different adipose depots determined after euthanasia and dissection of the different depots), whereas the EC50 of the glucose metabolism was

  14. Road transport and diet affect metabolic response to exercise in horses.

    Connysson, M; Muhonen, S; Jansson, A

    2017-11-01

    This study investigated the effects of transport and diet on metabolic response during a subsequent race-like test in Standardbred horses in training fed a forage-only diet and a 50:50 forage:oats diet. Six trained and raced Standardbred trotter mares were used. Two diets, 1 forage-only diet (FONLY) and 1 diet with 50% of DM intake from forage and 50% from oats (FOATS), were fed for two 29-d periods in a crossover design. At Day 21, the horses were subjected to transport for 100 km before and after they performed an exercise test (transport test [TT]). At Day 26, the horses performed a control test (CT), in which they were kept in their stall before and after the exercise test. Blood samples were collected throughout the study, and heart rate and water intake were recorded. Heart rate and plasma cortisol, glucose, and NEFA concentrations were greater for the TT than for the CT ( = 0.008, = 0.020, = 0.010, and = 0.0002, respectively) but were not affected by diet. Plasma acetate concentration was lower during the TT than during the CT ( = 0.034) and greater for the FONLY than for the FOATS ( = 0.003). There were no overall effects of the TT compared with the CT on total plasma protein concentration (TPP), but TPP was lower with the FONLY than with the FOATS ( = 0.016). There was no overall effect of the TT compared with the CT on water intake, but water intake was greater with the FONLY than the FOATS ( = 0.011). There were no overall effects of transport or diet on BW, plasma lactate, or plasma urea concentration. It was concluded that both transport and diet affect metabolic response during exercise in horses. Aerobic energy supply was most likely elevated by transportation and by the FONLY. The FONLY also decreased exercise-induced effects on extracellular fluid regulation. These results highlight the importance of experimental design in nutrition studies. If the aim is to examine how a diet affects exercise response in competition horses, transport should

  15. Modulation of the growth and metabolic response of cyanobacteria by the multifaceted activity of naringenin.

    Beata Żyszka

    Full Text Available The interactions between the plant-derived bioflavonoid, naringenin, and prokaryotic microalgae representatives (cyanobacteria, were investigated with respect to its influence on the growth and metabolic response of these microorganisms. To achieve reliable results, the growth of cyanobacteria was determined based on measurements of chlorophyll content, morphological changes were assessed through microscopic observations, and the chemical response of cells was determined using liquid and gas chromatography (HPLC; GC-FID. The results show that micromolar levels of naringenin stimulated the growth of cyanobacteria. Increased growth was observed for halophilic strains at naringenin concentrations below 40 mg L-1, and in freshwater strains at concentrations below 20 mg L-1. The most remarkable stimulation was observed for the freshwater species Nostoc muscorum, which had a growth rate that was up to 60% higher than in the control. When naringenin was examined at concentrations above 40 mg L-1, the growth of the tested microorganisms was inhibited. Simultaneously, an intensive excretion of exopolysaccharides was observed. Microscopic observations strongly suggest that these effects resulted from a structural disturbance of cyanobacterial cell walls that was exerted by naringenin. This phenomenon, in combination with the absorption of naringenin into cell wall structures, influenced cell permeability and thus the growth of bacteria. Fortunately, almost all the naringenin added to the culture was incorporated into to cell substructures and could be recovered through extraction, raising the possibility that this modulator could be recycled.

  16. Consistency of metabolic responses and appetite sensations under postabsorptive and postprandial conditions.

    Gonzalez, Javier T; Veasey, Rachel C; Rumbold, Penny L S; Stevenson, Emma J

    2012-10-01

    The present study aimed to investigate the reliability of metabolic and subjective appetite responses under fasted conditions and following consumption of a cereal-based breakfast. Twelve healthy, physically active males completed two postabsorption (PA) and two postprandial (PP) trials in a randomised order. In PP trials a cereal based breakfast providing 1859 kJ of energy was consumed. Expired gas samples were used to estimate energy expenditure and fat oxidation and 100mm visual analogue scales were used to determine appetite sensations at baseline and every 30 min for 120 min. Reliability was assessed using limits of agreement, coefficient of variation (CV), intraclass coefficient of correlation and 95% confidence limits of typical error. The limits of agreement and typical error were 292.0 and 105.5 kJ for total energy expenditure, 9.3 and 3.4 g for total fat oxidation and 22.9 and 8.3mm for time-averaged AUC for hunger sensations, respectively over the 120 min period in the PP trial. The reliability of energy expenditure and appetite in the 2h response to a cereal-based breakfast would suggest that an intervention requires a 211 kJ and 16.6mm difference in total postprandial energy expenditure and time-averaged hunger AUC to be meaningful, fat oxidation would require a 6.7 g difference which may not be sensitive to most meal manipulations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Anastasia V. Ponasenko

    2017-01-01

    Full Text Available Infective endocarditis (IE is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

  18. Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

    Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

    2017-01-01

    Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

  19. Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

    Fangcong Dong

    Full Text Available Bacteremia, the presence of viable bacteria in the blood stream, is often associated with several clinical conditions. Bacteremia can lead to multiple organ failure if managed incorrectly, which makes providing suitable nutritional support vital for reducing bacteremia-associated mortality. In order to provide such information, we investigated the metabolic consequences of a Klebsiella pneumoniae (K. pneumoniae infection in vivo by employing a combination of (1H nuclear magnetic resonance spectroscopy and multivariate data analysis. K. pneumoniae was intravenously infused in rats; urine and plasma samples were collected at different time intervals. We found that K. pneumoniae-induced bacteremia stimulated glycolysis and the tricarboxylic acid cycle and also promoted oxidation of fatty acids and creatine phosphate to facilitate the energy-demanding host response. In addition, K. pneumoniae bacteremia also induced anti-endotoxin, anti-inflammatory and anti-oxidization responses in the host. Furthermore, bacteremia could cause a disturbance in the gut microbiotal functions as suggested by alterations in a range of amines and bacteria-host co-metabolites. Our results suggest that supplementation with glucose and a high-fat and choline-rich diet could ameliorate the burdens associated with bacteremia. Our research provides underlying pathological processes of bacteremia and a better understanding of the clinical and biochemical manifestations of bacteremia.

  20. Plasticity in habitat use determines metabolic response of fish to global warming in stratified lakes.

    Busch, Susan; Kirillin, Georgiy; Mehner, Thomas

    2012-09-01

    We used a coupled lake physics and bioenergetics-based foraging model to evaluate how the plasticity in habitat use modifies the seasonal metabolic response of two sympatric cold-water fishes (vendace and Fontane cisco, Coregonus spp.) under a global warming scenario for the year 2100. In different simulations, the vertically migrating species performed either a plastic strategy (behavioral thermoregulation) by shifting their population depth at night to maintain the temperatures occupied at current in-situ observations, or a fixed strategy (no thermoregulation) by keeping their occupied depths at night but facing modified temperatures. The lake physics model predicted higher temperatures above 20 m and lower temperatures below 20 m in response to warming. Using temperature-zooplankton relationships, the density of zooplankton prey was predicted to increase at the surface, but to decrease in hypolimnetic waters. Simulating the fixed strategy, growth was enhanced only for the deeper-living cisco due to the shift in thermal regime at about 20 m. In contrast, simulating the plastic strategy, individual growth of cisco and young vendace was predicted to increase compared to growth currently observed in the lake. Only growth rates of older vendace are reduced under future global warming scenarios irrespective of the behavioral strategy. However, performing behavioral thermoregulation would drive both species into the same depth layers, and hence will erode vertical microhabitat segregation and intensify inter-specific competition between the coexisting coregonids.

  1. Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women.

    Moazzami, Ali A; Shrestha, Aahana; Morrison, David A; Poutanen, Kaisa; Mykkänen, Hannu

    2014-06-01

    Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P insulin. Women with higher fasting concentrations of leucine and isoleucine and lower fasting concentrations of sphingomyelins and phosphatidylcholines had higher insulin responses despite similar glucose concentration after all kinds of bread (cross-validated ANOVA, P = 0.048). High blood concentration of branched-chain amino acids, i.e., leucine and isoleucine, has been associated with the increased risk of diabetes, which suggests that additional consideration should be given to bread proteins in understanding the beneficial health effects of different kinds of breads. The present study suggests that the fasting metabolic profile can be used to characterize the postprandial insulin demand in individuals with normal glucose metabolism that can be used for establishing strategies for the stratification of individuals in personalized nutrition. © 2014 American Society for Nutrition.

  2. The metabolic and temporal basis of muscle hypertrophy in response to resistance exercise.

    Brook, Matthew S; Wilkinson, Daniel J; Smith, Kenneth; Atherton, Philip J

    2016-09-01

    Constituting ∼40% of body mass, skeletal muscle has essential locomotory and metabolic functions. As such, an insight into the control of muscle mass is of great importance for maintaining health and quality-of-life into older age, under conditions of cachectic disease and with rehabilitation. In healthy weight-bearing individuals, muscle mass is maintained by the equilibrium between muscle protein synthesis (MPS) and muscle protein breakdown; when this balance tips in favour of MPS hypertrophy occurs. Despite considerable research into pharmacological/nutraceutical interventions, resistance exercise training (RE-T) remains the most potent stimulator of MPS and hypertrophy (in the majority of individuals). However, the mechanism(s) and time course of hypertrophic responses to RE-T remain poorly understood. We would suggest that available data are very much in favour of the notion that the majority of hypertrophy occurs in the early phases of RE-T (though still controversial to some) and that, for the most part, continued gains are hard to come by. Whilst the mechanisms of muscle hypertrophy represent the culmination of mechanical, auto/paracrine and endocrine events, the measurement of MPS remains a cornerstone for understanding the control of hypertrophy - mainly because it is the underlying driving force behind skeletal muscle hypertrophy. Development of sophisticated isotopic techniques (i.e. deuterium oxide) that lend to longer term insight into the control of hypertrophy by sustained RE-T will be paramount in providing insights into the metabolic and temporal regulation of hypertrophy. Such technologies will have broad application in muscle mass intervention for both athletes and for mitigating disease/age-related cachexia and sarcopenia, alike.

  3. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  4. Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities.

    Lindh, Markus V; Figueroa, Daniela; Sjöstedt, Johanna; Baltar, Federico; Lundin, Daniel; Andersson, Agneta; Legrand, Catherine; Pinhassi, Jarone

    2015-01-01

    Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, increasing loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2) and Bothnian Sea (salinity 3.6) water. Baltic Proper bacteria generally reached higher abundances than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating a replacement effect. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating an adjustment effect. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, a priming effect resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial ecosystem process rates.

  5. Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities

    Markus V Lindh

    2015-04-01

    Full Text Available Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, intensifying loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2 and Bothnian Sea (salinity 3.6 water. Baltic Proper bacteria generally reached higher abundance than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating a higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating replacement. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating adjustment. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, the original triggering, or priming effect, resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment, and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial

  6. Metabolic response to different glycemic indexes of pre-exercise meal

    Valéria Cristina de Faria

    2015-08-01

    Full Text Available INTRODUCTION: To ensure performance and health, the type of food and the time of pre-exercise ingestion should be considered by practitioners of morning physical activity. Objective: This study assessed the metabolic response after pre-exercise meals with different glycemic indexes (GI and in the fasting state adopting different types of hydration.METHODS: Twelve men performed four experimental tests; two with pre-exercise meals of high GI (HGI and low GI (LGI, and two were performed in the fasting state with hydration: water (H2O and carbohydrate drink (CHO. Each test consisted of a pre-exercise rest period of 30 minutes followed by 60 minutes of cycle ergometer with continuous load equivalent to 60% of the extrapolated maximal oxygen consumption (VO2MaxExt. During the exercise, participants were hydrated every 15 minutes with 3mL per kg body weight. During each experimental test, venous blood samples were obtained for fasting and at 15-minute intervals during rest, and every 20 minutes during exercise. The gas analysis was carried out in periods of 5 minutes every 20 minutes of exercise.RESULTS: There was no difference in substrate oxidation. After 20 minutes of exercise, pre-exercise food intake procedures showed similar behavior, having only reduced blood glucose levels compared to fasting procedures (p<0.01. There was maintenance of blood glucose at stable and higher levels during exercise in relation to the other tests in the fast procedure with CHO.CONCLUSION: The data suggest that despite the similar metabolic behavior between LGI and HGI meals, the adoption of a LGI meal before the morning exercise seems to be a more suitable feeding practice due to higher tendency of rebound hypoglycemia after HGI meal and when morning exercise is performed on fasting, hydration with CHO seems to minimize the hypoglycemic risk arising from that state.

  7. Similar metabolic responses in pigs and humans to breads with different contents and compositions of dietary fibers: a metabolomics study

    Nielsen, Kirstine Lykke; Hartvigsen, Merete; Hedemann, Mette Skou

    2014-01-01

    Background: In nutritional studies, pigs are often used as models for humans because of nutritional and physiologic similarities. However, evidence supporting similar metabolic responses to nutritional interventions is lacking. Objective: The objective was to establish whether pigs and humans...... respond similarly to a nutritional intervention. Using metabolomics, we compared the acute metabolic response to 4 test breads between conventional pigs (growing) and adult human subjects (with the metabolic syndrome). Design: Six catheterized pigs and 15 human subjects were tested in a randomized...... different basal metabolome concentrations in the plasma of pigs and humans. Humans had higher contents of phosphatidylcholines, oleic acid, and carnitine in plasma, possibly reflecting a higher intake of meats and fats. In pigs, betaine, choline, creatinine, tryptophan, and phenylalanine were higher...

  8. Antioxidant gene expression and metabolic responses of earthworms (Eisenia fetida) after exposure to various concentrations of hexabromocyclododecane.

    Shi, Yajuan; Xu, Xiangbo; Chen, Juan; Liang, Ruoyu; Zheng, Xiaoqi; Shi, Yajing; Wang, Yurong

    2018-01-01

    Hexabromocyclododecane (HBCD), a ubiquitous suspected contaminant, is one of the world's most prominent brominated flame retardants (BFRs). In the present study, earthworms (Eisenia fetida) were exposed to HBCD. The expression of selected antioxidant enzyme genes was measured, and the metabolic responses were assessed using nuclear magnetic resonance (NMR) to identify the molecular mechanism of the antioxidant stress reaction and the metabolic reactions of earthworms to HBCD. A significant up-regulation (p  0.05). Principal component analysis (PCA) of the metabolic responses showed that all groups could be clearly differentiated, and the highest concentration dose group was the most distant from the control group. Except for fumarate, the measured metabolites, which included adenosine triphosphate (ATP), valine, lysine, glycine, betaine and lactate, revealed significant (p earthworm exposure studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways.

    Morvan, Daniel; Demidem, Aicha

    2007-03-01

    Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment.

  10. Paradoxical bleeding and thrombosis in a patient with afibrinogenemia and fibrinogen Mumbai mutation.

    Mukaddam, Alfiya; Patil, Rucha; Jadli, Anshul; Chandrakala, S; Ghosh, Kanjaksha; Shetty, Shrimati

    2015-05-01

    Thrombosis is rarely reported in cases of afibrinogenemia and is generally associated with thrombophilia or replacement therapy. Often, it is difficult to predict whether the patients will bleed or whether they are exposed to the risk of thrombosis. We report a patient with afibrinogenemia who presented with complete thrombosis of right hepatic, portal, and splenic veins and who described a lifelong history of bleeding. Direct sequencing of the three fibrinogen genes was performed to identify the mutation. DNA sequencing showed the presence of a homozygous for G8017A substitution in exon 8 of the fibrinogen β-chain gene, resulting in a G434D missense mutation (Fibrinogen Mumbai). Presence of both bleeding and thrombotic manifestations in a patient with afibrinogenemia in the presence of other associated risk factors warrants a very careful individualized approach in the management of patients with afibrinogenemia. Copyright© by the American Society for Clinical Pathology.

  11. Elevated plasma fibrinogen, psychological distress, antidepressant use, and hospitalization with depression

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne

    2013-01-01

    with depression in the general population. METHODS: We examined 73,367 20-100 year old men and women from two large population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study. We measured plasma fibrinogen and recorded symptoms of psychological distress, use......OBJECTIVES: Low-grade systemic inflammation may contribute to the development of depression. We tested the hypothesis that elevated plasma levels of the inflammatory marker fibrinogen are associated with psychological distress, use of antidepressant medication, and with hospitalization...... of antidepressant medication, and hospitalization with depression in both cross-sectional and prospective studies. RESULTS: In cross-sectional analyses, a stepwise increase in fibrinogen percentile categories was associated with a stepwise increase in risk of psychological distress, use of antidepressant medication...

  12. Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

    Martino V. Franchi

    2017-07-01

    Full Text Available Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively; however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT is assumed to produce greater hypertrophy than concentric resistance training (CON RT. Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

  13. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    Manoj K Bhasin

    Full Text Available The relaxation response (RR is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS as top upregulated critical molecules (focus hubs and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

  14. Thermal and metabolic responses of military divers during a 6-hour static dive in cold water.

    Riera, Florence; Horr, Reed; Xu, Xiaojiang; Melin, Bruno; Regnard, Jacques; Bourdon, Lionel

    2014-05-01

    Human thermal responses during prolonged whole-body immersion in cold water are of interest for the military, especially French SEALS. This study aims at describing the thermo-physiological responses. There were 10 male military divers who were randomly assigned to a full immersion in neutral (34 degrees C), moderately cold (18 degrees C), and cold (10 degrees C) water wearing their operational protective devices (5.5 mm wetsuit with 3.0 mm thick underwear) for 6 h in a static position. Rectal temperature (T(re)) and 14 skin temperatures (T(sk)), blood analysis (stress biomarkers, metabolic substrates), and oxygen consumption (Vo2) were collected. At 34 degrees C, there were no significant modifications of the thermo-physiological responses over time. The most interesting result was that rates of rectal temperature decrease (0.15 +/- 0.02 degrees C x min(-1)) were the same between the two cold stress experimental conditions (at 18 degrees C and 10 degrees C). At the final experiment, rectal temperature was not significantly different between the two cold stress experimental conditions. Mean T(sk) decreased significantly during the first 3 h of immersion and then stabilized at a lower level at 10 degrees C (25.6 +/- 0.8 degrees C) than at 18 degrees C (29.3 +/- 0.9 degrees C). Other results demonstrate that the well-trained subjects developed effective physiological reactions. However, these reactions are consistently too low to counterbalance the heat losses induced by cold temperature conditions and long-duration immersion. This study shows that providing divers with thermal protection is efficient for a long-duration immersion from a medical point of view, but not from an operational one when skin extremities were taken into account.

  15. Telling metabolic stories to explore metabolomics data -- A case study on the Yeast response to cadmium exposure

    P.V. Milreu (Paulo); C.C. Klein (Cecilia); L. Cottret; V. Acuña (Vicente); E. Birmele; M. Borassi; C. Junot; A. Marchetti Spaccamela (Alberto); A. Morino; L. Stougie (Leen); F. Jourdan; P. Crescenzi; V. Lacroix; M.-F. Sagot (Marie-France)

    2014-01-01

    htmlabstractMotivation: The increasing availability of metabolomics data enables to better understand the metabolic processes involved in the immediate response of an organism to environmental changes and stress. The data usually come in the form of a list of metabolites whose concentrations

  16. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole

    1983-01-01

    -insulin to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism...

  17. Metabolic response to 36 hours of fasting in young men born small vs appropriate for gestational age

    Jørgensen, Sine W; Brøns, Charlotte; Bluck, Les

    2015-01-01

    AIMS/HYPOTHESIS: Being born small for gestational age (SGA) is associated with an increased risk of type 2 diabetes in an affluent society, but could confer an improved chance of survival during sparse living conditions. We studied whether insulin action and other metabolic responses to prolonged...

  18. The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans

    ter Horst, Kasper W.; Gilijamse, Pim W.; Demirkiran, Ahmet; van Wagensveld, Bart A.; Ackermans, Mariette T.; Verheij, Joanne; Romijn, Johannes A.; Nieuwdorp, Max; Maratos-Flier, Eleftheria; Herman, Mark A.; Serlie, Mireille J.

    2017-01-01

    Objective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion.

  19. Predictive value of PET response combined with baseline metabolic tumor volume in peripheral T-cell lymphoma patients

    Cottereau, Anne-Segolene; El-Galaly, Tarec C; Becker, Stéphanie

    2018-01-01

    Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes with current therapy. We investigated if response assessed with Positron Emission Tomography/computed tomography (PET/CT) combined with baseline total metabolic tumor volume (TMTV) co...

  20. Metabolic response of porcine colon explants to in vitro infection by Brachyspira hyodysenteriae : a leap into disease pathophysiology

    Welle, Thijs; Hoekstra, Anna T.; Daemen, Ineke A.J.J.M.; Berkers, Celia R.; de Oliveira Costa, Matheus

    2017-01-01

    Introduction: Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available. Objective: The aim of this study was to characterize the metabolic response of porcine colon

  1. Metabolic and transcriptional responses of gilthead sea bream (Sparus aurata L.) to environmental stress: New insights in fish mitochondrial phenotyping

    Bermejo-Nogales, A.; Nederlof, M.A.J.; Benedito-Palos, L.; Ballester-Lozano, G.F.; Folkedal, O.; Olsen, R.E.; Sitjà-Bobadilla, A.; Pérez-Sánchez, J.

    2014-01-01

    The aim of the current study was to phenotype fish metabolism and the transcriptionally-mediated response of hepatic mitochondria of gilthead sea bream to intermittent and repetitive environmental stressors: (i) changes in water temperature (T-ST), (ii) changes in water level and chasing (C-ST) and

  2. Hydroxyl radical-modified fibrinogen as a marker of thrombosis: the role of iron.

    Lipinski, B; Pretorius, E

    2012-07-01

    Excessive free iron in blood and in organ tissues (so called iron overload) has been observed in degenerative diseases such as atherosclerosis, cancer, neurological, and certain autoimmune diseases, in which fibrin-like deposits are also found. Although most of the body iron is bound to hemoglobin and myoglobin in a divalent ferrous form, a certain amount of iron exists in blood as a trivalent (ferric) ion. This particular chemical state of iron has been shown to be toxic to the human body when not controlled by endogenous and/or dietary chelating agents. Experiments described in this paper show for the first time that ferric ions (Fe(3+)) can generate hydroxyl radicals without participation of any redox agent, thus making it a special case of the Fenton reaction. Ferric chloride was also demonstrated to induce aggregation of purified fibrinogen at the same molar concentrations that were used for the generation of hydroxyl radicals. Iron-aggregated fibrinogen, by contrast to native molecule, could not be dissociated into polypeptide subunit chains as shown in a polyacrylamide gel electrophoresis. The mechanism of this phenomenon is very likely based on hydroxyl radical-induced modification of fibrinogen tertiary structure with the formation of insoluble aggregates resistant to enzymatic and chemical degradations. Soluble modified fibrinogen species can be determined in blood of thrombotic patients by the reaction with protamine sulfate and/or by scanning electron microscopy. In view of these findings, it is postulated that iron-induced alterations in fibrinogen structure is involved in pathogenesis of certain degenerative diseases associated with iron overload and persistent thrombosis. It is concluded that the detection of hydroxyl radical-modified fibrinogen may be utilized as a marker of a thrombotic condition in human subjects.

  3. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  4. Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle.

    Ruby, Maxwell A; Riedl, Isabelle; Massart, Julie; Åhlin, Marcus; Zierath, Juleen R

    2017-10-01

    Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism. Copyright © 2017 the American Physiological Society.

  5. Metabolic responses to prolonged work during treadmill and water immersion running.

    Frangolias, D D; Rhodes, E C; Taunton, J E; Belcastro, A N; Coutts, K D

    2000-12-01

    The primary aim of this study was to compare the physiological responses to prolonged treadmill (TM) and water immersion to the neck (WI) running at threshold intensity. Ten endurance runners performed TM and WI running VO2max tests. Subjects completed submaximal performance tests at ventilatory threshold (Tvent) intensities under TM and WI conditions and responses at 15 and 42 minutes examined. VO2 was lower in WI (p<0.05) at maximal effort and Tvent. The Tvent VO2 intensities interpolated from the TM and WI VO2max tests were performed in both TM (i.e., TM@TM(tvent),TM@WI(tvent), corresponding to 77.6 and 71.3% respectively of TM VO2max) and WI conditions (i.e., WI@TM(tvent), WI@WI(tvent), corresponding to 85.5% and 78.2% respectively of WI VO2max). Each of the dependent variables was analyzed using a 3-way repeated measures ANOVA (2 conditions X 2 exercise intensities X 7 time points during exercise). VO2max values were significantly lower in the WI (52.4(5.1) ml.kg(-1) min(-1)) versus TM (59.7(6.5) ml.kg(-1) min(-1)) condition. VO2 during submaximal tests were similar during the TM and WI conditions. HR and [BLa] responses to exercise at and above WI(tvent) were similar during short-term exercise, but values tended to be lower during prolonged exercise in the WI condition. There were no statistical differences in VE responses in the 2 conditions, however as with HR and [BLa] an upward trend was noted with TM exercise over the 42 minute duration of the tests. RPE at WI(tvent) was similar for TM and WI exercise sessions, however, RPE at TM(tvent) was higher during WI compared to TM running. Cardiovascular drift was observed during prolonged TM but not WI running. Results suggest differences in metabolic responses to prolonged submaximal exercise in WI, however it can be used effectively for cross training.

  6. Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition.

    Le Roy, Caroline Ivanne; Passey, Jade Louise; Woodward, Martin John; La Ragione, Roberto Marcello; Claus, Sandrine Paule

    2017-06-01

    Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1 H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Extracellular fibrinogen-binding protein (Efb) from staphylococcus aureus Inhibits the formation of platelet-leukocyte complexes

    Posner, M.G; Upadhyay, A.; Abubaker, A.A.; Fortunato, T.M.; Vara, D.; Canobbio, I.; Bagby, S.; Pula, G.

    2016-01-01

    Extracellular fibrinogen-binding protein (Efb) from Staphylococcus aureus inhibits platelet activation, although its mechanism of action has not been established. In this study, we discovered that the N-terminal region of Efb (Efb-N) promotes platelet binding of fibrinogen and that Efb-N binding to

  8. Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men

    Cigolini, M; Targher, G; de Sandre, G; Muggeo, M; Seidell, J C

    Recent prospective studies have reported an independent association between fibrinogen plasma levels and risk of cardiovascular events. Aim of this study was to investigate the relationships between fibrinogen level and conventional cardiovascular risk factors in a random sample of 38 year-old

  9. In vitro sealing of iatrogenic fetal membrane defects by a collagen plug imbued with fibrinogen and plasma.

    Engels, A C; Hoylaerts, M F; Endo, M; Loyen, S; Verbist, G; Manodoro, S; DeKoninck, P; Richter, J; Deprest, J A

    2013-02-01

    We aimed to demonstrate local thrombin generation by fetal membranes, as well as its ability to generate fibrin from fibrinogen concentrate. Furthermore, we aimed to investigate the efficacy of collagen plugs, soaked with plasma and fibrinogen, to seal iatrogenic fetal membrane defects. Thrombin generation by homogenized fetal membranes was measured by calibrated automated thrombography. To identify the coagulation caused by an iatrogenic membrane defect, we analyzed fibrin formation by optical densitometry, upon various concentrations of fibrinogen. The ability of a collagen plug soaked with fibrinogen and plasma was tested in an ex vivo model for its ability to seal an iatrogenic fetal membrane defect. Fetal membrane homogenates potently induced thrombin generation in amniotic fluid and diluted plasma. Upon the addition of fibrinogen concentrate, potent fibrin formation was triggered. Measured by densiometry, fibrin formation was optimal at 1250 µg/mL fibrinogen in combination with 4% plasma. A collagen plug soaked with fibrinogen and plasma sealed an iatrogenic membrane defect about 35% better than collagen plugs without these additives (P = 0.037). These in vitro experiments suggest that the addition of fibrinogen and plasma may enhance the sealing efficacy of collagen plugs in closing iatrogenic fetal membrane defects. © 2013 John Wiley & Sons, Ltd.

  10. Aerobic metabolism and cardioventilatory responses in paraplegic athletes during an incremental wheelchair exercise.

    Vinet, A; Le Gallais, D; Bernard, P L; Poulain, M; Varray, A; Mercier, J; Micallef, J P

    1997-01-01

    The aims of the present study were: (1) to assess aerobic metabolism in paraplegic (P) athletes (spinal lesion level, T4-L3) by means of peak oxygen uptake (VO2peak) and ventilatory threshold (VT), and (2) to determine the nature of exercise limitation in these athletes by means of cardioventilatory responses at peak exercise. Eight P athletes underwent conventional spirographic measurements and then performed an incremental wheelchair exercise on an adapted treadmill. Ventilatory data were collected every minute using an automated metabolic system: ventilation (l x min[-1]), oxygen uptake (VO2, l x min[-1], ml x min[-1] x kg[-1]), carbon dioxide production (VCO2, ml x min[-1]), respiratory exchange ratio, breathing frequency and tidal volume. Heart rate (HR, beats x min[-1]) was collected with the aid of a standard electrocardiogram. VO2peak was determined using conventional criteria. VT was determined by the breakpoint in the VCO2 - VO2 relationship, and is expressed as the absolute VT (VO2, ml x min[-1] x kg[-1]) and relative VT (percentage of VO2peak). Spirometric values and cardioventilatory responses at rest and at peak exercise allowed the measurement of ventilatory reserve (VR), heart rate reserve (HRr), heart rate response (HRR), and O2 pulse (O2 P). Results showed a VO2peak value of 40.6 (2.5) ml x min(-1) x kg(-1), an absolute VT detected at 23.1 (1.5) ml x min(-1) x kg(-1) VO2 and a relative VT at 56.4 (2.2)% VO2peak. HRr [15.8 (3.2) beats min(-1)], HRR [48.6 (4.3) beat x l(-1)], and O2 P [0.23 (0.02) ml x kg(-1) x beat(-1)] were normal, whereas VR at peak exercise [42.7 (2.4)%] was increased. As wheelchair exercise excluded the use of an able-bodied (AB) control group, we compared our VO2peak and VT results with those for other P subjects and AB controls reported in the literature, and we compared our cardioventilatory responses with those for respiratory and cardiac patients. The low VO2peak values obtained compared with subject values obtained during

  11. Epigenetic control and the circadian clock: linking metabolism to neuronal responses.

    Orozco-Solis, R; Sassone-Corsi, P

    2014-04-04

    Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. Published by Elsevier Ltd.

  12. Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism

    Yang, Wei; Bai, Yibing; Xiong, Ying; Zhang, Jin; Chen, Shuokai; Zheng, Xiaojun; Meng, Xiangbo; Li, Lunyi; Wang, Jing; Xu, Chenguang; Yan, Chengsong; Wang, Lijuan; Chang, Catharine C. Y.; Chang, Ta-Yuan; Zhang, Ti; Zhou, Penghui; Song, Bao-Liang; Liu, Wanli; Sun, Shao-cong; Liu, Xiaolong; Li, Bo-liang; Xu, Chenqi

    2016-01-01

    CD8+ T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment1–4. Reactivating the cytotoxicity of CD8+ T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8+ T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme5, led to potentiated effector function and enhanced proliferation of CD8+ but not CD4+ T cells. This is due to the increase in the plasma membrane cholesterol level of CD8+ T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8+ T cells were better than wild-type CD8+ T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile6,7, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy. PMID:26982734

  13. Cross-Talk between Carbon Metabolism and the DNA Damage Response in S. cerevisiae

    Kobi J. Simpson-Lavy

    2015-09-01

    Full Text Available Yeast cells with DNA damage avoid respiration, presumably because products of oxidative metabolism can be harmful to DNA. We show that DNA damage inhibits the activity of the Snf1 (AMP-activated protein kinase (AMPK, which activates expression of genes required for respiration. Glucose and DNA damage upregulate SUMOylation of Snf1, catalyzed by the SUMO E3 ligase Mms21, which inhibits SNF1 activity. The DNA damage checkpoint kinases Mec1/ATR and Tel1/ATM, as well as the nutrient-sensing protein kinase A (PKA, regulate Mms21 activity toward Snf1. Mec1 and Tel1 are required for two SNF1-regulated processes—glucose sensing and ADH2 gene expression—even without exogenous genotoxic stress. Our results imply that inhibition of Snf1 by SUMOylation is a mechanism by which cells lower their respiration in response to DNA damage. This raises the possibility that activation of DNA damage checkpoint mechanisms could contribute to aerobic fermentation (Warburg effect, a hallmark of cancer cells.

  14. THE EFFECT OF ADRENAL MEDULLECTOMY ON METABOLIC RESPONSES TO CHRONIC INTERMITTENT HYPOXIA

    Shin, Mi-Kyung; Han, Woobum; Bevans-Fonti, Shannon; Jun, Jonathan C.; Punjabi, Naresh M.; Polotsky, Vsevolod Y.

    2014-01-01

    Obstructive sleep apnea causes intermittent hypoxia (IH) and is associated with insulin resistance and type 2 diabetes. IH increases plasma catecholamine levels, which may increase insulin resistance and suppress insulin secretion. The objective of this study was to determine if adrenal medullectomy (MED) prevents metabolic dysfunction in IH. MED or sham surgery was performed in 60 male C57BL/6J mice, which were then exposed to IH or control conditions (intermittent air) for 6 weeks. IH increased plasma epinephrine and norepinephrine levels, increased fasting blood glucose and lowered basal and glucose-stimulated insulin secretion. MED decreased baseline epinephrine and prevented the IH induced increase in epinephrine, whereas the norepinephrine response remained intact. MED improved glucose tolerance in mice exposed to IH, attenuated the impairment in basal and glucose-stimulated insulin secretion, but did not prevent IH-induced fasting hyperglycemia or insulin resistance. We conclude that the epinephrine release from the adrenal medulla during IH suppresses insulin secretion causing hyperglycemia. PMID:25179887

  15. The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism

    Yoichiro eMitsuishi

    2012-12-01

    Full Text Available The Keap1-Nrf2 pathway plays a central role in the protection of cells against oxidative and xenobiotic stresses. Nrf2 is a potent transcription activator that recognizes a unique DNA sequence known as the antioxidant response element (ARE. Under normal conditions, Nrf2 binds to Keap1 in the cytoplasm, resulting in proteasomal degradation. Following exposure to electrophiles or reactive oxygen species, Nrf2 becomes stabilized, translocates into the nucleus and activates the transcription of various cytoprotective genes. Increasing attention has been paid to the role of Nrf2 in cancer cells because the constitutive stabilization of Nrf2 has been observed in many human cancers with poor prognosis. Recent studies have shown that the antioxidant and detoxification activities of Nrf2 confer chemo- and radio-resistance to cancer cells. In this review, we provide an overview of the Keap1-Nrf2 system and discuss its role under physiological and pathological conditions, including cancers. We also introduce the results of our recent study describing Nrf2 function in the metabolism of cancer cells. Nrf2 likely confers a growth advantage to cancer cells through enhancing cytoprotection and anabolism. Finally, we discuss the possible impact of Nrf2 inhibitors on cancer therapy.

  16. Circulatory and muscle metabolic responses to draught work compared to increasing trotting velocities.

    Gottlieb, M; Essén-Gustavsson, B; Lindholm, A; Persson, S G

    1988-11-01

    Circulatory and muscle metabolic responses were studied in 10 horses which all performed incremental draught work at a low trotting speed on a treadmill (D-test) and also exercise with gradually increasing velocities (S-test). Exercise was continued until the horses could no longer maintain the weights above the floor or maintain speed trotting without changing gait to a gallop. Muscle biopsies were taken from the gluteus and the semitendinosus muscles before, and immediately after, exercise. The heart rate (HR) increased linearly with both increasing draught resistance and velocity and reached mean values of 212 and 203 beats/min, respectively. Blood lactate levels increased exponentially to mean values of 12.9 and 7.9 mmol/litre in the two tests. Both HR and blood lactate levels were significantly higher at the cessation of work in the D-test compared to the S-test. The relationship between HR and blood lactate response in the S-test was similar to that in the D-test. The red cell volume was determined after a standardised exercise tolerance test and was significantly correlated both to the weightloading and to the velocity, producing a HR of 200 beats/min. The changes seen in muscle glycogen and glucose-6-phosphate were similar in the two tests, whereas significantly higher lactate levels and lower creatine phosphate and adenosine triphosphate levels were seen in the D-test compared to the S-test. It was concluded that high oxidative capacity is of importance both for fast trotting and for draught work.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Evaluation of plasma fibrinogen concentration as a diagnostic indicator of inflammation in red-eared sliders (Trachemys scripta elegans).

    Moore, A Russell; Allender, Matthew C; Mitchell, Mark A; MacNeill, Amy L

    2015-01-15

    To critically evaluate plasma fibrinogen concentration as a diagnostic indicator of inflammation in red-eared sliders (Trachemys scripta elegans). Prospective induced-disease model and prospective cross-sectional study. Plasma samples from 12 purpose-bred red-eared sliders and 153 farm-raised red-eared sliders. A modification of the Jacobsson method was developed to measure fibrinogen concentration in platelet-poor plasma from red-eared sliders. Purpose-bred turtles had been inoculated with a ranavirus (n = 4) or sterile PBS solution (8) as part of another study. Farm-raised red-eared sliders were categorized as healthy (n = 138) or overtly ill (15) on the basis of physical examination findings at the time of blood sample collection. Samples from 124 of the 138 healthy red-eared sliders were used to establish a fibrinogen concentration reference interval as measured by the modified Jacobsson method. Fibrinogen concentrations in ranavirus-infected and physically ill turtles were compared with those of healthy turtles to determine whether fibrinogen concentration would be a useful diagnostic indicator of inflammation in red-eared sliders. The modified Jacobsson method was reliably used to measure fibrinogen concentration. The fibrinogen concentration reference interval from healthy reproductively active female red-eared sliders was right skewed. Fibrinogen concentration did not differ significantly between healthy red-eared sliders and ranavirus-infected or overtly ill red-eared sliders. A reference interval for red-eared slider plasma fibrinogen concentration was established and partitioned by sex to account for considerable right skewing observed for females. Fibrinogen concentration was not a useful indicator of inflammation in red-eared sliders with ranavirus infection or other overt illnesses.

  18. In situ assembly of fibrinogen/hyaluronic acid hydrogel via knob-hole interaction for 3D cellular engineering

    Shengjie Huang

    2017-12-01

    Full Text Available Hyaluronic acid (HA-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability. However, the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility. Inspired by the crosslinking mechanism of fibrin gel, a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA (knob-g-HA in this study. The knob-grafted HA was synthesized by coupling knob peptides (GPRPAAC, a mimic peptide of fibrin knob A to HA via Michael addition. Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2. The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50, 100 and 200 mg/mL were evaluated, and it was found that the dynamic storage moduli (G′ were higher than the loss moduli (G″ over the whole frequency range for all the groups. The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels. Correspondingly, a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel. Finally, the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test. All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.

  19. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

    Catoire, Milène; Alex, Sheril; Paraskevopulos, Nicolas

    2014-01-01

    Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercis...

  20. Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

    Xiaoxia Gao

    2018-01-01

    Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

  1. Robust metabolic responses to varied carbon sources in natural and laboratory strains of Saccharomyces cerevisiae.

    Wayne A Van Voorhies

    Full Text Available Understanding factors that regulate the metabolism and growth of an organism is of fundamental biologic interest. This study compared the influence of two different carbon substrates, dextrose and galactose, on the metabolic and growth rates of the yeast Saccharomyces cerevisiae. Yeast metabolic and growth rates varied widely depending on the metabolic substrate supplied. The metabolic and growth rates of a yeast strain maintained under long-term laboratory conditions was compared to strain isolated from natural condition when grown on different substrates. Previous studies had determined that there are numerous genetic differences between these two strains. However, the overall metabolic and growth rates of a wild isolate of yeast was very similar to that of a strain that had been maintained under laboratory conditions for many decades. This indicates that, at in least this case, metabolism and growth appear to be well buffered against genetic differences. Metabolic rate and cell number did not co-vary in a simple linear manner. When grown in either dextrose or galactose, both strains showed a growth pattern in which the number of cells continued to increase well after the metabolic rate began a sharp decline. Previous studied have reported that O₂ consumption in S. cerevisiae grown in reduced dextrose levels were elevated compared to higher levels. Low dextrose levels have been proposed to induce caloric restriction and increase life span in yeast. However, there was no evidence that reduced levels of dextrose increased metabolic rates, measured by either O₂ consumption or CO₂ production, in the strains used in this study.

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

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    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

  3. Common motifs in the response of cereal primary metabolism to fungal pathogens are not based on similar transcriptional reprogramming

    Lars Matthias Voll

    2011-08-01

    Full Text Available During compatible interactions with their host plants, biotrophic plant pathogens subvert host metabolism to ensure the sustained provision of nutrient assimilates by the colonized host cells. To investigate, whether common motifs can be revealed in the response of primary carbon and nitrogen metabolism towards colonization with biotrophic fungi in cereal leaves, we have conducted a combined metabolome and transcriptome study of three quite divergent pathosystems, the barley powdery mildew fungus (Blumeria graminis f.sp. hordei, the corn smut fungus Ustilago maydis and the maize anthracnose fungus Colletotrichum graminicola, the latter being a hemibiotroph that only exhibits an initial biotrophic phase during its establishment.Based on the analysis of 42 water-soluble metabolites, we were able to separate early biotrophic from late biotrophic interactions by hierarchical cluster analysis and principal component analysis, irrespective of the plant host. Interestingly, the corresponding transcriptome dataset could not discriminate between these stages of biotrophy, irrespective, of whether transcript data for genes of central metabolism or the entire transcriptome dataset was used. Strong differences in the transcriptional regulation of photosynthesis, glycolysis, the TCA cycle, lipid biosynthesis, and cell wall metabolism were observed between the pathosystems. Increased contents of Gln, Asn, and glucose as well as diminished contents of PEP and 3-PGA were common to early post-penetration stages of all interactions. On the transcriptional level, genes of the TCA cycle, nucleotide energy metabolism and amino acid biosynthesis exhibited consistent trends among the compared biotrophic interactions, identifying the requirement for metabolic energy and the rearrangement of amino acid pools as common transcriptional motifs during early biotrophy. Both metabolome and transcript data were employed to generate models of leaf primary metabolism during

  4. [Supposed role of "metabolic memory" in formation of response reaction to stress-factors in young and adult organisms].

    Bozhkov, A I; Dlubovskaia, V L; Dmitriev, Iu V; Meshaĭkina, N I; Maleev, V A; Klimova, E M

    2009-01-01

    The influence of the combined long-lasted influences of sulfur sulfate and diet restriction in young (3 month age) and adult (21 month age) Vistar rats on activity of glucose-6-phospatase, alaninaminotranspherase (ALT), aspartataminotranspherase (AST), and on phosphorilating activity of liver mitochondria was studied to investigate the role of metabolic memory on the peculiarities of response reaction. The young animals not differed from adult ones in the possibility of inducing activity of glucose-6-phospatase, ALT, and on phosphorilating activity after the influence of sulfur sulfate and diet restriction. The age-related differences in glucose-6-phospatase and transpherases and phosphorilating activity existing in control disappeared after the long-lasted action of sulfur sulfate and diet restriction. The answer reaction in enzyme activity to stress factors applied many times depends upon the metabolic memory formed in the process of adaptation, and the age of animals have no influence on it. In some relation the ontogenesis may be considered as a result of adaptation genesis. The metabolic memory can change the answer of the system to the stress influence. There are three types of modification of the answer to stress factors: the answer remains unchanged (metabolic memory), "paradox answer" formation, and super activation of the metabolic system.

  5. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    P.S. de Vries (Paul); D.I. Chasman (Daniel); M. Sabater-Lleal (Maria); M.-H. Chen (Ming-Huei); J.E. Huffman (Jennifer E.); M. Steri (Maristella); W. Tang (Weihong); A. Teumer (Alexander); R.E. Marioni (Riccardo); V. Grossmann (Vera); J.J. Hottenga (Jouke Jan); S. Trompet (Stella); M. Müller-Nurasyid (Martina); J.H. Zhao (Jing Hua); J. Brody (Jennifer); M.E. Kleber (Marcus); X. Guo (Xiuqing); J.J. Wang (Jie Jin); P. Auer (Paul); J. Attia (John); L.R. Yanek (Lisa); T.S. Ahluwalia (Tarunveer Singh); J. Lahti (Jari); C. Venturini (Cristina); T. Tanaka (Toshiko); L.F. Bielak (Lawrence F.); P.K. Joshi (Peter); A. Rocanin-Arjo (Ares); I. Kolcic (Ivana); P. Navarro (Pau); L.M. Rose (Lynda); C. Oldmeadow (Christopher); H. Riess (Helene); J. Mazur (Johanna); S. Basu (Saonli); A. Goel (Anuj); Q. Yang (Qiong); M. Ghanbari (Mohsen); Gonnekewillemsen; A. Rumley (Ann); E. Fiorillo (Edoardo); A.J. de Craen (Anton); A. Grotevendt (Anne); R.A. Scott (Robert); K.D. Taylor (Kent D.); G.E. Delgado (Graciela E.); J. Yao (Jie); A. Kifley (Annette); C. Kooperberg (Charles); Q. Qayyum (Rehan); L. Lopez (Lornam); T.L. Berentzen (Tina L.); K. Räikkönen (Katri); Massimomangino; S. Bandinelli (Stefania); P.A. Peyser (Patricia A.); S. Wild (Sarah); D.-A. Tregouet (David-Alexandre); A.F. Wright (Alan); J. Marten (Jonathan); T. Zemunik (Tatijana); A.C. Morrison (Alanna); B. Sennblad (Bengt); G.H. Tofler (Geoffrey); M.P.M. de Maat (Moniek); E.J.C. de Geus (Eco); G.D. Lowe (Gordon D.); M. Zoledziewska (Magdalena); N. Sattar (Naveed); H. Binder (Harald); U. Völker (Uwe); M. Waldenberger (Melanie); K.-T. Khaw (Kay-Tee); B. McKnight (Barbara); J. Huang (Jian); N.S. Jenny (Nancy); E.G. Holliday (Elizabeth); L. Qi (Lihong); M.G. Mcevoy (Mark G.); D.M. Becker (Diane); J.M. Starr (John); A.-P. Sarin; P.G. Hysi (Pirro); D.G. Hernandez (Dena); M.A. Jhun (Min A.); H. Campbell (Harry); A. Hamsten (Anders); F. Sarin (Fernando); W.L. McArdle (Wendy); P. Eline Slagboom; T. Zeller (Tanja); W. Koenig (Wolfgang); B. Psaty (Brucem); T. Haritunians (Talin); J. Liu (Jingmin); A. Palotie (Aarno); A.G. Uitterlinden (André); D.J. Stott (David J.); A. Hofman (Albert); O.H. Franco (Oscar); O. Polasek (Ozren); I. Rudan (Igor); P.-E. Morange (P.); J.F. Wilson (James F.); S.L. Kardia (Sharon L.r); L. Ferrucci (Luigi); T.D. Spector (Timothy); J.G. Eriksson (Johan G.); T. Hansen (Torben); I.J. Deary (Ian); L.C. Becker (Lewis); R.J. Scott (Rodney); P. Mitchell (Paul); W. März (Winfried); N.J. Wareham (Nick J.); A. Peters (Annette); A. Greinacher (Andreas); P.S. Wild (Philipp S.); J.W. Jukema (Jan Wouter); D.I. Boomsma (Dorret I.); C. Hayward (Caroline); F. Cucca (Francesco); R.P. Tracy (Russell); H. Watkins (Hugh); A.P. Reiner (Alex P.); A.R. Folsom (Aaron); P.M. Ridker (Paul); C.J. O'Donnell (Christopher J.); N.L. Smith (Nicholas L.); D.P. Strachan (David P.); A. Dehghan (Abbas)

    2016-01-01

    textabstractGenome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes

  6. Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity.

    Gonçalo da Costa

    Full Text Available Familial amyloidotic polyneuropathy (FAP is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR. This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.

  7. The effect of Ramadan fasting and physical activity on homocysteine and fibrinogen concentrations in overweight women

    Seyyed Reza Attarzadeh Hosseini

    2014-12-01

    Full Text Available Introduction: Increased levels of certain markers like fibrinogen and Homocysteine are independently associated with an increased risk of cardiovascular diseases. Considering the numerous favorable effects of healthful nutrition and physical activity on reducing the risk of atherosclerosis, in this study we intend to take into account fasting and physical activity during the month of Ramadan and their impacts on Homocysteine and fibrinogen concentrations in overweight women. Materials and Methods: In this experiment, 22 overweight and obese women with a body mass index (BMI of greater than 25 kg/m2 aging from 20 to 45 years were enrolled into two groups by means of targeted-sampling method. One group involved fasting accompanied with regular physical activity (12 subjects and the other group involved only fasting (10 subjects. The protocol for the physical activity group consisted of three 60-minute sessions of aerobic exercise per week with a 50%- 65% heart rate reserved. Towards the end of Ramadan, the anthropometric and blood levels of Homocysteine and fibrinogen were closely measured. Data were analyzed using repeated measures and the significance level of P≤0 /05 was considered. Findings: A month of fasting along with regular physical activity did not prove to have any noticeable effects on the level of fibrinogen while a significant increase in the Homocysteine levels was discovered (P

  8. The conversion of fibrinogen to fibrin: A brief history of some key events.

    Doolittle, Russell F

    2017-07-01

    The conversion of fibrinogen to fibrin is a process that has long fascinated an army of researchers. In this brief review some early break-through observations are noted and a few later unexpected results described. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Abnormal fibrinogen Zlín (.gamma.Thr21Ile) with missense mutation causing hypofibrinogenemia

    Riedelová-Reicheltová, Z.; Riedel, Tomáš; Májek, P.; Kotlín, R.; Geierová, V.; Suttnar, J.; Dyr, J. E.

    2014-01-01

    Roč. 132, č. 2 (2014), s. 140-143 ISSN 0001-5792 R&D Projects: GA ČR GBP205/12/G118 Institutional support: RVO:61389013 Keywords : fibrinogen * missense mutation * hypofibrinogenemia Subject RIV: BO - Biophysics Impact factor: 1.116, year: 2014

  10. Study of albumin and fibrinogen membranes formed by interfacial crosslinking using microfluidic flow

    Chang Hong; Khan, Rachel; Rong, Zimei; Vadgama, Pankaj [IRC in Biomedical Materials, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Sapelkin, Andrei, E-mail: p.vadgama@qmul.ac.u [Department of Physics, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom)

    2010-09-15

    Microfluidics enables scale reduction in sample volume with obvious benefits for reagent conservation. In contrast to conventional macro-scale flow, microfluidics also offers unprecedented control over flow dynamics. In particular, laminar flow is readily achieved, allowing for new analytical and synthetic strategies. Here, two parallel flows of buffer and xylene were used to create a stable liquid-liquid interface within linear micro-channels. These, respectively, carried protein (albumin or fibrinogen) and an acyl chloride to effect protein crosslinking. This created robust, micro-membranes at the interface that bisected the fluid channel. Membrane formation was self-limiting, with fibrinogen membranes showing greater solute permeability than albumin, based on dye transport (Ponceau S, Meldola Blue). The crosslinker isophthaloyl dichloride led to thinner, less permeable membranes than terephthaloyl chloride. Larger surface area membranes formed at a static liquid-liquid interface served as a more physically accessible model and allowed precise electrochemical determination of acetaminophen, catechol and peroxide diffusion coefficients, which confirmed the greater fibrinogen permeability. Scanning electron microscopy (SEM) of the membranes also indicated a higher population of discrete nanopores at the fibrinogen surface. A crosslinking pH had a strong effect on overall permeability. Adhesion of B50 neuronal cells was demonstrated, and it is proposed that the membranes could facilitate cell growth through bidirectional nutrient supply in a micrbioreactor format.

  11. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria

    2016-01-01

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. W...

  12. Source of fibrin/fibrinogen degradation products in the CSF after subarachnoid hemorrhage

    Vermeulen, M.; van Vliet, H. H.; Lindsay, K. W.; Hijdra, A.; van Gijn, J.

    1985-01-01

    In 48 patients with a subarachnoid hemorrhage, levels of fibrin/fibrinogen degradation products (FDP's), total protein, and plasminogen were measured in the cerebrospinal fluid (CSF) between Days 9 and 15 after the bleed. Of these 48 patients, 22 received tranexamic acid. Despite a significant

  13. A novel fibrinogen variant - Liberec: dysfibrinogenaemia associated with gamma Tyr262Cys substitution

    Kotlín, R.; Sobotková, A.; Suttnar, J.; Salaj, P.; Walterová, L.; Riedel, Tomáš; Reicheltová, Z.; Dyr, J. E.

    2008-01-01

    Roč. 81, č. 2 (2008), s. 123-129 ISSN 0902-4441 R&D Projects: GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z40500505 Keywords : fibrinogen * missense mutation * dysfibrinogenaemia Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.237, year: 2008

  14. A novel fibrinogen variant - Praha I: hypofibrinogenemia associated with .gamma. Gly351Ser substitution

    Kotlín, R.; Chytilová, M.; Suttnar, J.; Salaj, P.; Riedel, Tomáš; Šantrůček, J.; Klener, P.; Dyr, J. E.

    2007-01-01

    Roč. 78, č. 5 (2007), s. 410-416 ISSN 0902-4441 Institutional research plan: CEZ:AV0Z40500505 Keywords : fibrinogen * missense mutation * hypofibrinogenemia Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.163, year: 2007

  15. Group B streptococcal serine-rich repeat proteins promote interaction with fibrinogen and vaginal colonization.

    Wang, Nai-Yu; Patras, Kathryn A; Seo, Ho Seong; Cavaco, Courtney K; Rösler, Berenice; Neely, Melody N; Sullam, Paul M; Doran, Kelly S

    2014-09-15

    Group B streptococcus (GBS) can cause severe disease in susceptible hosts, including newborns, pregnant women, and the elderly. GBS serine-rich repeat (Srr) surface glycoproteins are important adhesins/invasins in multiple host tissues, including the vagina. However, exact molecular mechanisms contributing to their importance in colonization are unknown. We have recently determined that Srr proteins contain a fibrinogen-binding region (BR) and hypothesize that Srr-mediated fibrinogen binding may contribute to GBS cervicovaginal colonization. In this study, we observed that fibrinogen enhanced wild-type GBS attachment to cervical and vaginal epithelium, and that this was dependent on Srr1. Moreover, purified Srr1-BR peptide bound directly to host cells, and peptide administration in vivo reduced GBS recovery from the vaginal tract. Furthermore, a GBS mutant strain lacking only the Srr1 "latching" domain exhibited decreased adherence in vitro and decreased persistence in a mouse model of GBS vaginal colonization, suggesting the importance of Srr-fibrinogen interactions in the female reproductive tract. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Beta-fibrinogen allele frequencies in Peruvian Quechua, a high-altitude native population.

    Rupert, J L; Devine, D V; Monsalve, M V; Hochachka, P W

    1999-06-01

    Elevated hematocrits, which are found in many high-altitude populations, increase the oxygen-carrying capacity of blood and may represent an adaptation to hypoxic environments. However, as high hematocrit increases blood viscosity, which in turn is associated with hypertension and heart disease, it may be advantageous for high-altitude populations to limit other factors that contribute to increased blood viscosity. One such factor is the plasma concentration of the coagulation protein fibrinogen. Several common polymorphisms in the beta-fibrinogen gene have been identified that affect fibrinogen concentrations. We determined the allele frequencies of three of these polymorphisms (G/A-455(HaeIII), C/T-148(HindIII), and G/A+448(MnlI)) in sample groups drawn from three populations: Quechua-speaking natives living at over 3,200 m in the Peruvian Andes, North American natives (Na-Dene) from coastal British Columbia, and Caucasian North Americans. The frequencies of the alleles previously shown to be associated with increased fibrinogen levels were so low in the Quechuas that their presence could be accounted for solely by genetic admixture with Caucasians. Frequencies in the Na-Dene, a Native American group unrelated to the Quechua, were not significantly different from those in Caucasians.

  17. Plasma levels of C-Reactive Protein and Fibrinogen in Pulmonary ...

    In this study, we determined the changes in plasma C- reactive protein (C-RP) and Fibrinogen levels in Drug sensitive Tuberculosis (DSTB) patients at diagnosis, Multi drug resistant tuberculosis (MDRTB) patients at diagnosis and during chemotherapy. Twenty-four (24) patients MDRTB patients and 24 newly diagnosed ...

  18. Pilot Randomized trial of Fibrinogen in Trauma Haemorrhage (PRooF-iTH)

    Steinmetz, Jacob; Henriksen, Hanne Hee; Sørensen, Anne Marie

    2016-01-01

    bleeding related to trauma, so scientific guardians will co-sign the informed consent form. Next of kin and the patients’ general practitioner or the patients will co-sign as soon as possible.This trial will test whether immediate pre-emptive fibrinogen concentrate administered to adult trauma patients...

  19. Oxidative stress protection and glutathione metabolism in response to hydrogen peroxide and menadione in riboflavinogenic fungus Ashbya gossypii.

    Kavitha, S; Chandra, T S

    2014-11-01

    Ashbya gossypii is a plant pathogen and a natural overproducer of riboflavin and is used for industrial riboflavin production. A few literature reports depict a link between riboflavin overproduction and stress in this fungus. However, the stress protection mechanisms and glutathione metabolism are not much explored in A. gossypii. In the present study, an increase in the activity of catalase and superoxide dismutase was observed in response to hydrogen peroxide and menadione. The lipid peroxide and membrane lipid peroxide levels were increased by H2O2 and menadione, indicating oxidative damage. The glutathione metabolism was altered with a significant increase in oxidized glutathione (GSSG), glutathione peroxidase (GPX), glutathione S transferase (GST), and glutathione reductase (GR) and a decrease in reduced glutathione (GSH) levels in the presence of H2O2 and menadione. Expression of the genes involved in stress mechanism was analyzed in response to the stressors by semiquantitative RT-PCR. The messenger RNA (mRNA) levels of CTT1, SOD1, GSH1, YAP1, and RIB3 were increased by H2O2 and menadione, indicating the effect of stress at the transcriptional level. A preliminary bioinformatics study for the presence of stress response elements (STRE)/Yap response elements (YRE) depicted that the glutathione metabolic genes, stress genes, and the RIB genes hosted either STRE/YRE, which may enable induction of these genes during stress.

  20. Ozone modifies the metabolic and endocrine response to glucose: Reproduction of effects with the stress hormone corticosterone.

    Thomson, Errol M; Pilon, Shinjini; Guénette, Josée; Williams, Andrew; Holloway, Alison C

    2018-03-01

    Air pollution is associated with increased incidence of metabolic disease (e.g. metabolic syndrome, obesity, diabetes); however, underlying mechanisms are poorly understood. Air pollutants increase the release of stress hormones (human cortisol, rodent corticosterone), which could contribute to metabolic dysregulation. We assessed acute effects of ozone, and stress axis involvement, on glucose tolerance and on the metabolic (triglyceride), endocrine/energy regulation (insulin, glucagon, GLP-1, leptin, ghrelin, corticosterone), and inflammatory/endothelial (TNF, IL-6, VEGF, PAI-1) response to exogenous glucose. Male Fischer-344 rats were exposed to clean air or 0.8 ppm ozone for 4 h in whole body chambers. Hypothalamic-pituitary-adrenal (HPA) axis involvement in ozone effects was tested through subcutaneous administration of the glucocorticoid synthesis inhibitor metyrapone (50 mg/kg body weight), corticosterone (10 mg/kg body weight), or vehicle (40% propylene glycol) prior to exposure. A glucose tolerance test (2 g/kg body weight glucose) was conducted immediately after exposure, with blood samples collected at 0, 30, 60, 90, and 120 min. Ozone exposure impaired glucose tolerance, an effect accompanied by increased plasma triglycerides but no impairment of insulin release. Ozone diminished glucagon, GLP-1, and ghrelin responses to glucose, but did not significantly impact inflammatory/endothelial analytes. Metyrapone reduced corticosterone but increased glucose and triglycerides, complicating evaluation of the impact of glucocorticoid inhibition. However, administration of corticosterone reproduced the profile of ozone effects, supporting a role for the HPA axis. The results show that ozone-dependent changes in glucose tolerance are accompanied by altered metabolic and endocrine responses to glucose challenge that are reproduced by exogenous stress hormone. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  1. Dynamical feedback between circadian clock and sucrose availability explains adaptive response of starch metabolism to various photoperiods

    Francois Gabriel Feugier

    2013-01-01

    Full Text Available Plants deal with resource management during all their life. During the day they feed on photosynthetic carbon, sucrose, while storing a part into starch for night use. Careful control of carbon partitioning, starch degradation and sucrose export rates is crucial to avoid carbon starvation, insuring optimal growth whatever the photoperiod. Efficient regulation of these key metabolic rates can give an evolutionary advantage to plants. Here we propose a model of adaptive starch metabolism in response to various photoperiods. We assume the three key metabolic rates to be circadian regulated in leaves and that their phases of oscillations are shifted in response to sucrose starvation. We performed gradient descents for various photoperiod conditions to find the corresponding optimal sets of phase shifts that minimize starvation. Results at convergence were all consistent with experimental data: i diurnal starch profile showed linear increase during the day and linear decrease at night; ii shorter photoperiod tended to increase starch synthesis speed while decreasing its degradation speed during the longer night; iii sudden early dusk showed slower starch degradation during the longer night. Profiles that best explained observations corresponded to circadian regulation of all rates. This theoretical study would establish a framework for future research on feedback between starch metabolism and circadian clock as well as plant productivity.

  2. Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

    Oksana Shynlova

    2013-04-01

    Full Text Available Objectives To analyze the expression of genes involved in extracellular matrix (ECM biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP. Materials and Methods This study examined the expression of matrix metalloproteinases (MMPs, their tissue inhibitors (TIMPs, and the Lysyl oxidase (LOX family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10 vs. proliferative (group 2, n = 8 phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2 vs. postmenopausal controls (group 3, n = 5. Finally, we analyzed postmenopausal controls (group 3 vs. postmenopausal women with advanced POP (group 4, n = 13. Results According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003, whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01 when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly. TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both. Conclusions Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause.

  3. PEG-induced osmotic stress in Mentha x piperita L.: Structural features and metabolic responses.

    Búfalo, Jennifer; Rodrigues, Tatiane Maria; de Almeida, Luiz Fernando Rolim; Tozin, Luiz Ricardo Dos Santos; Marques, Marcia Ortiz Mayo; Boaro, Carmen Silvia Fernandes

    2016-08-01

    The present study investigated whether osmotic stress induced by the exposure of peppermint (Mentha x piperita L.) to moderate and severe stress for short periods of time changes the plant's physiological parameters, leaf anatomy and ultrastructure and essential oil. Plants were exposed to two levels of polyethyleneglycol (50 g L(-1) and 100 g L(-1) of PEG) in a hydroponic experiment. The plants exposed to 50 g L(-1) maintained metabolic functions similar to those of the control group (0 g L(-1)) without changes in gas exchange or structural characteristics. The increase in antioxidant enzyme activity reduced the presence of free radicals and protected membranes, including chloroplasts and mitochondria. In contrast, the osmotic stress caused by 100 g L(-1) of PEG inhibited leaf gas exchange, reduced the essential oil content and changed the oil composition, including a decrease in menthone and an increase in menthofuran. These plants also showed an increase in peroxidase activity, but this increase was not sufficient to decrease the lipid peroxidation level responsible for damaging the membranes of organelles. Morphological changes were correlated with the evaluated physiological features: plants exposed to 100 g L(-1) of PEG showed areas with collapsed cells, increases in mesophyll thickness and the area of the intercellular space, cuticle shrinkage, morphological changes in plastids, and lysis of mitochondria. In summary, our results revealed that PEG-induced osmotic stress in M. x piperita depends on the intensity level of the osmotic stress applied; severe osmotic stress changed the structural characteristics, caused damage at the cellular level, and reduced the essential oil content and quality. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus.

    Nguyen, Long The; Saad, Sonia; Tan, Yi; Pollock, Carol; Chen, Hui

    2017-07-01

    Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity. © 2017 Society for Endocrinology.

  5. Circulatory, respiratory and metabolic responses in Thoroughbred horses during the first 400 meters of exercise.

    Littlejohn, A; Snow, D H

    1988-01-01

    These studies investigated circulatory, respiratory and metabolic responses in four Thoroughbred geldings during the first 400 metres of galloping (mean speed 14.4 +/- 0.38 m.s-1), cantering (mean speed 10.0 +/- 0.61 m.s-1) and walking (mean speed 1.58 +/- 0.05 m.s-1) from a standing start. A radio-controlled device which collected blood samples anaerobically during each 100 m section of the exercise track allowed analyses of changes in and functional relationships of the variables measured. During the 400 m gallop, the mean heart rate (HR) increased from 125 to 201 beats.min-1 and the haematocrit (Hct) from 0.513 to 0.589 l/l-1. The haemoglobin [Hb], lactate [LA] and potassium [K+] concentrations increased significantly, while the pH and the partial pressure of oxygen (PaO2) decreased significantly. The arterial partial pressure of carbon dioxide (PaCO2) and the plasma bicarbonate concentration did not change significantly. There were significant correlations between HR and Hct, HR and [Hb], HR and PaO2, HR and pH, HR and PvCO2, HR and [LA], HR and [K+], pH and [K+], Hct and PaO2, [Hb] and PaO2, PaCO2 and PaO2, [LA] and PaO2, pH and PaO2, [K+] and PaO2, stride frequency and PaO2. With the exception of the PvCO2 which increased significantly, changes in venous blood during the gallop were in the same direction as those of arterial blood. Thirty seconds before the start of the gallop, both HR and [Hb] were significantly higher than at rest, providing an approximate three-fold increase in oxygen delivery compared to that of the resting state.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Dimensionality controls cytoskeleton assembly and metabolism of fibroblast cells in response to rigidity and shape.

    Mirjam Ochsner

    2010-03-01

    Full Text Available Various physical parameters, including substrate rigidity, size of adhesive islands and micro-and nano-topographies, have been shown to differentially regulate cell fate in two-dimensional (2-D cell cultures. Cells anchored in a three-dimensional (3-D microenvironment show significantly altered phenotypes, from altered cell adhesions, to cell migration and differentiation. Yet, no systematic analysis has been performed that studied how the integrated cellular responses to the physical characteristics of the environment are regulated by dimensionality (2-D versus 3-D.Arrays of 5 or 10 microm deep microwells were fabricated in polydimethylsiloxane (PDMS. The actin cytoskeleton was compared for single primary fibroblasts adhering either to microfabricated adhesive islands (2-D or trapped in microwells (3-D of controlled size, shape, and wall rigidity. On rigid substrates (Young's Modulus = 1 MPa, cytoskeleton assembly within single fibroblast cells occurred in 3-D microwells of circular, rectangular, square, and triangular shapes with 2-D projected surface areas (microwell bottom surface area and total surface areas of adhesion (microwell bottom plus wall surface area that inhibited stress fiber assembly in 2-D. In contrast, cells did not assemble a detectable actin cytoskeleton in soft 3-D microwells (20 kPa, regardless of their shapes, but did so on flat, 2-D substrates. The dependency on environmental dimensionality was also reflected by cell viability and metabolism as probed by mitochondrial activities. Both were upregulated in 3-D cultured cells versus cells on 2-D patterns when surface area of adhesion and rigidity were held constant.These data indicate that cell shape and rigidity are not orthogonal parameters directing cell fate. The sensory toolbox of cells integrates mechanical (rigidity and topographical (shape and dimensionality information differently when cell adhesions are confined to 2-D or occur in a 3-D space.

  7. Interaction of fibrinogen and albumin with titanium dioxide nanoparticles of different crystalline phases

    Marucco, Arianna; Fenoglio, Ivana; Turci, Francesco; Fubini, Bice

    2013-01-01

    TiO 2 nanoparticles (NPs) are contained in different kinds of industrial products including paints, self-cleaning glasses, sunscreens. TiO 2 is also employed in photocatalysis and it has been proposed for waste water treatment. Micrometric TiO 2 is generally considered a safe material, while there is concern on the possible health effects of nanometric titania. Due to their small size NPs may migrate within the human body possibly entering in the blood stream. Therefore studies on the interaction of NPs with plasma proteins are needed. In fact, the interaction with proteins is believed to ultimately influences the NPs biological fate. Fibrinogen and albumin are two of the most abundant plasma proteins. They are involved in several important physiological functions. Furthermore, fibrinogen is known to trigger platelet adhesion and inflammation. For these reasons the study of the interaction between these protein and nanoparticles is an important step toward the understanding of the behavior of NPs in the body. In this study we investigated the interaction of albumin and fibrinogen with TiO 2 nanoparticles of different crystal phases (rutile and anatase) using an integrated set of techniques. The amount of adsorbed fibrinogen and albumin for each TiO 2 surface was investigated by using the bicinchoninic acid assay (BCA). The variation of the surface charge of the NP-protein conjugates respect to the naked NPs was used to indirectly estimate both surface coverage and reversibility of the adsorption upon dilution. Surface charge was monitored by measuring the ζ potential with a conventional electrophoretic light scattering (ELS) system. The extent of protein deformation was evaluated by Raman Spectroscopy. We found that both proteins adsorb irreversibly against electrostatic repulsion, likely undergoing conformational changes or selective orientation upon adsorption. The size of primary particles and the particles aggregation rather than the crystal phase modulate the

  8. Metabolic Responses to Sago and Soy Supplementations during Endurance Cycling Performance in the Heat

    Daniel Tarmast

    2017-10-01

    Full Text Available This study examined the effects of Sago (Sa, Soy (So, combined iso–caloric Sago+Soy (SS supplementations during cycling on metabolic responses as compared to placebo (P in the heat (31℃, 70% relative humidity. Twelve well–trained male cyclists (Age: 19.0±5.6 yr, Height: 170.8±7.6 cm, Wight: 60.1±11.2 kg, and VO2max: 56.5±6.5 mL.kg-1.min-1 participated in four experimental trials. The design of the trials was a randomized single–blind, placebo–controlled crossover trail comprising 90 min of steady–state cycling on an ergometer at 60% of VO2max followed by a 20–km time trial performance (TT. The participants of the study were supplemented 5 times at 0, 20, 40, 60, and 80 minutes during the steady–state cycling. Sa, So, and SS supplements provided 7.5% Sago, 7.5% Soy, and 6.0% Sago + 1.5% Soy respectively. Plasma glucose concentrations (PG reached a peak at 60 min after ingestion of Sa and SS as compared to baseline. At the end of the TT, PG reduced significantly to the baseline level. Plasma insulin concentrations (PI increased in all trials, but reduced gradually to the baseline level. The concentration of plasma free fatty acids (FFA increased gradually during the steady–state cycling and TT, and FFA was significantly higher in the P and So than the Sa and SS trials. At the end of the steady–state cycling, the plasma lactate concentration (LACT reached its lowest concentrations and at the end of the TT was enhanced significantly in all trials. These results suggest that sago and soy supplements increase the PG and PI during endurance exercise in the heat. These data add to the growing body of knowledge concerning endurance athletes’ glycemic and insulinemic responses to carbohydrate consumptions during exercise in the heat.

  9. Air pollution and neuroendocrine stress-mediated systemic metabolic and inflammatory response

    New experimental evidence involving the role of neuroendocrine activation challenges an accepted mechanistic paradigm of how irritant air pollutants induce systemic metabolic impairment and lung injury/inflammation. We focus on recent air pollution studies highlighting how the re...

  10. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    Baud, Maxime O.; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J.; Petit, Jean-Marie

    2016-01-01

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs

  11. The effect of metabolic alkalosis on the ventilatory response in healthy subjects

    Mos-Oppersma, Eline; Doorduin, Jonne; van der Hoeven, J.G.; Veltink, Petrus H.; van Hees, H.W.H.; Heunks, L.M.A.

    Background Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma

  12. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

    Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

    2017-09-05

    Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Correlating metabolic and anatomic responses of primary lung cancers to radiotherapy by combined F-18 FDG PET-CT imaging

    Grills Inga

    2007-05-01

    Full Text Available Abstract Background To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy. Methods 36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters was correlated with that of maximum standard uptake value (SUV of the primary lung cancer before and after conventional radiotherapy. Results There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p Conclusion Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.

  14. Differential metabolic responses of Beauveria bassiana cultured in pupae extracts, root exudates and its interactions with insect and plant.

    Luo, Feifei; Wang, Qian; Yin, Chunlin; Ge, Yinglu; Hu, Fenglin; Huang, Bo; Zhou, Hong; Bao, Guanhu; Wang, Bin; Lu, Ruili; Li, Zengzhi

    2015-09-01

    and distilled water. This indicates that fungal fatty acid metabolism is enhanced when contacting insect, but when in the absence of insect hosts NRP synthesis is increased. Ornithine, arginine and GABA are decreased in mycelia cultured in pupae extracts and root exudates but remain unchanged in distilled water, which suggests that they may be associated with fungal cross-talk with insects and plants. Trehalose and mannitol are decreased while adenine is increased in three conditions, signifying carbon shortage in cells. Together, these results unveil that B. bassiana has differential metabolic responses in pupae extracts and root exudates, and metabolic similarity in root exudates and distilled water is possibly due to the lack of insect components. Copyright © 2015. Published by Elsevier Inc.

  15. Insulin Responsiveness in Metabolic Syndrome after Eight Weeks of Cycle Training

    Stuart, Charles A.; South, Mark A.; Lee, Michelle L.; McCurry, Melanie P.; Howell, Mary E. A.; Ramsey, Michael W.; Stone, Michael H.

    2013-01-01

    Introduction Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Methods Eighteen non-diabetic, sedentary subjects, eleven with the metabolic syndrome, participated in eight weeks of increasing intensity stationary cycle training. Results Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (VO2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. Activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of 2x fibers decreased with a concomitant increase in 2a mixed fibers in the control subjects, but in metabolic syndrome, 2x fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups and GLUT4 expression increased in the metabolic syndrome subjects. Excess phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. Conclusion In the absence of weight loss, cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis, and increased expression of insulin receptors and GLUT4 in muscle, but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337 and this is not ameliorated by eight weeks of endurance exercise training. PMID:23669880

  16. Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration.

    Petit Jean-Marie; Tobler Irene; Kopp Caroline; Morgenthaler Florence; Borbély Alexander A; Magistretti Pierre J

    2010-01-01

    STUDY OBJECTIVES The main energy reserve of the brain is glycogen which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here we extended our investigations to another set of genes related to glycogen and glucose metabolism. We also compared the effect of instrumentally and pharmacologically induced prolonged wakefulness followed (or not) by 3...

  17. Polymorphism in beta fibrinogen -455 g/a gene was associated with diabetic in severe ischemic stroke patients

    Ritarwan, Kiking; Kadri, Alfansuri; Juwita Sembiring, Rosita

    2018-03-01

    There is a association of polymorphism in the promoter region of the beta fibrinogen gene -455 G/A with enhancement plasma fibrinogen level. Diabetes mellitus is a risk factor for early neurologic deterioration in acute ischemic stroke. The prothrombotic fibrinogen protein is frequently elevated in patients with diabetes and may be association with poorer prognosis. This study evaluated the association of beta fibrinogen gene -455 G/A promoter polymorphism on modified Ranking Scale of Ischemic Stroke patients treated with diabetic and nondiabetic group. In a Cohort study design comprises 200 consecutive patients diabetic and a nondiabetic who, three months using completed a detailed outcome stroke. Of 200 samples genotype distribution were 27.1% for GG+GA and 0% for AA with diabetic and than 4.4% for GG+GA and 0.05% diabetic patients. Fibrinogen levels were higher in diabetic than nondiabetic group patients (307.7 + 106.3 vs 278 + 84 gr/dl, p=0.002). Fibrinogen level was found to be an independent predictor for diabetic patients. On Genotype GG+GA were associated wth diabetic and nondiabetic group patients. Modified Rankin Scale on day 90 were found associated with diabetic and nondiabetic patients. Conclusion: Elevated fibrinogen level is dose-dependently associated with 90 days outcome severity stroke with diabetic following ischemic stroke

  18. Fibrinogen and thrombin concentrations are critical for fibrin glue adherence in rat high-risk colon anastomoses

    Eliseo Portilla-de Buen

    2014-04-01

    Full Text Available OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal or high-risk (ischemic end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL or low (40 mg/mL concentrations and thrombin at high (1000 IU/mL or low (500 IU/mL concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery.

  19. Association of Fibrinogen with Severity of Stable Coronary Artery Disease in Patients with Type 2 Diabetic Mellitus

    Li-Feng Hong

    2014-01-01

    Full Text Available Background. Some studies have suggested a relation of plasma fibrinogen to the severity of coronary artery disease (CAD. However, whether plasma fibrinogen can predict the presence and severity of CAD in patients with diabetes mellitus has not been determined. Methods. A total of consecutive 373 diabetic patients with typical angina pectoris who received coronary angiography were enrolled and classified into three groups by tertiles of Gensini score (GS, low group 28. The relationship between fibrinogen and GS was evaluated. Results. There were correlations of fibrinogen with hemoglobin A1c, C-reactive protein, and GS (r=0.17, r=0.52, and r=0.21, resp.; all P<0.001. Area under the receivers operating characteristic curve of fibrinogen was 0.62 (95% CI 0.56–0.68, P<0.001 for predicting a high GS. Multivariate analysis suggested that plasma fibrinogen was an independent predictor of a high GS for diabetic patients (OR=1.40, 95% CI 1.04–1.88, and P=0.026 after adjusting for traditional risk factors of CAD. Conclusions. The present data indicated that plasma fibrinogen, a readily measurable systematic inflammatory marker, appeared to be an independent predictor for the severity of CAD in diabetic patients.

  20. Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

    Kuehl, Linn K; Hinkelmann, Kim; Muhtz, Christoph; Dettenborn, Lucia; Wingenfeld, Katja; Spitzer, Carsten; Kirschbaum, Clemens; Wiedemann, Klaus; Otte, Christian

    2015-01-01

    Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, pcortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

    Jana Husse

    Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

  2. Mapping of residues of fibrinogen cleaved by protease II of Bacillus thuringiensis var. israelensis IMV B-7465

    E. M. Stohniy

    2016-04-01

    Full Text Available The limited proteolysis of macromolecules allows obtaining the fragments that preserve the structure and functional properties of the whole molecule and could be used in the study of proteins structure and function. Proteases targeted to fibrinogen and fibrin are of interest as the tool for obtaining of functionally active fragments of fibrin(ogen and for the direct defibrination in vivo. That is why the aim of the present work was to study the proteolytic action of Protease II (PII purified from Bacillus thuringiensis var. israelensis IMV B-7465 on fibrinogen. Hydrolysis products of fibrinogen by PII were analysed by SDS-PAGE under reducing conditions with further immunoprobing using the mouse monoclonal 1-5A (anti-Aα509-610 and ІІ-5С (anti-Aα20-78 antibodies. It was shown that PII cleaved preferentially the Aα-chain of fibrinogen splitting off the peptide with apparent molecular weight of 10 kDa that corresponded the C-terminal part of Aα-chain of fibrinogen molecule. MALDI-TOF analysis of hydrolysis of fibrinogen was performed using a Voyager-DE. Results analyzed by Data Explorer 4.0.0.0 allowed to detect the main peak occurring at mass/charge (M/Z ratio of 11 441 Da. According to “Peptide Mass Calculator” this peptide corresponded to fragment Аα505-610 of fibrinogen molecule. The result showed that PII cleaves the peptide bond AαAsp-Thr-Ala504-Ser505. Thus, PII can be used for the obtaining of unique fragments of fibrinogen molecule. As far as αC-domain contains numerous sites of fibrin intermolecular interactions we can consider PII as a prospective agent for their study and for the defibrination.

  3. Seasonal variations in the pattern of RNA metabolism of tuber tissue in response to excision and culture

    Macleod, A.J.; Mills, E.D.; Yeoman, M.M.

    1979-01-01

    Between December 1975 and June 1976 explants excised from Jerusalem artichoke tubers were cultured in the presence and in the absence of 2,4-D, the cells in the tissue dividing only in the presence of 2,4-D, in which the length of the first cell cycle increased nonlinearly from 18 hours to 40 hours as the tubers aged in storage at 4 0 C. Simultaneously the amount of RNA in the tissue declined linearly from 8 to 5 μg RNA per explant. Detailed examination of the RNA metabolism in dividing and in non-dividing cells during February and June 1976 revealed superimposed but independent responses to wounding during excision and to stimulation into growth by 2,4-D. The responses to wounding involved only a very low level of metabolic activity, were complete within a few hours of excision and changed very little with the storage of the tubers. Tissue treated with 2,4-D showed a much higher level of metabolic activity including the periodic accumulation of RNA coupled to its discontinuous synthesis. The features of these growth-related responses changed considerably during the investigation. (author)

  4. Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

    Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

    2013-10-01

    Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

  5. Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury.

    Evans, Nicholas; Hartigan, Clare; Kandilakis, Casey; Pharo, Elizabeth; Clesson, Ismari

    2015-01-01

    Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (V̇O2peak), average oxygen consumption (V̇O2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, V̇O2avg, and METssci. Exoskeleton-assisted walking resulted in %V̇O2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity.

  6. Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury

    Hartigan, Clare; Kandilakis, Casey; Pharo, Elizabeth; Clesson, Ismari

    2015-01-01

    Background: Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. Objective: The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. Methods: Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (V̇O2peak), average oxygen consumption (V̇O2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. Results: Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, V̇O2avg, and METssci. Exoskeleton-assisted walking resulted in %V̇O2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. Conclusion: Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity. PMID:26364281

  7. Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

    Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

    2011-01-01

    This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

  8. Acclimation temperature affects the metabolic response of amphibian skeletal muscle to insulin.

    Petersen, Ann M; Gleeson, Todd T

    2011-09-01

    Frog skeletal muscle mainly utilizes the substrates glucose and lactate for energy metabolism. The goal of this study was to determine the effect of insulin on the uptake and metabolic fate of lactate and glucose at rest in skeletal muscle of the American bullfrog, Lithobates catesbeiana, under varying temperature regimens. We hypothesize that lactate and glucose metabolic pathways will respond differently to the presence of insulin in cold versus warm acclimated frog tissues, suggesting an interaction between temperature and metabolism under varying environmental conditions. We employed radiolabeled tracer techniques to measure in vitro uptake, oxidation, and incorporation of glucose and lactate into glycogen by isolated muscles from bullfrogs acclimated to 5 °C (cold) or 25 °C (warm). Isolated bundles from Sartorius muscles were incubated at 5 °C, 15 °C, or 25 °C, and in the presence and absence of 0.05 IU/mL bovine insulin. Insulin treatment in the warm acclimated and incubated frogs resulted in an increase in glucose incorporation into glycogen, and an increase in intracellular [glucose] of 0.5 μmol/g (Pmuscle. When compared to the warm treatment group, cold acclimation and incubation resulted in increased rates of glucose oxidation and glycogen synthesis, and a reduction in free intracellular glucose levels (Pmuscles from either acclimation group were incubated at an intermediate temperature of 15 °C, insulin's effect on substrate metabolism was attenuated or even reversed. Therefore, a significant interaction between insulin and acclimation condition in controlling skeletal muscle metabolism appears to exist. Our findings further suggest that one of insulin's actions in frog muscle is to increase glucose incorporation into glycogen, and to reduce reliance on lactate as the primary metabolic fuel. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Increased Contractile Response to Noradrenaline Induced By Factors Associated with the Metabolic Syndrome in Cultured Small Mesenteric Arteries

    Blædel, Martin; Sams, Anette; Boonen, Harrie C M

    2016-01-01

    UNLABELLED: This study investigated the effect of the metabolic syndrome associated risk factors hyperglycemia (glucose [Glc]), hyperinsulinemia (insulin [Ins]) and low-grade inflammation (tumor necrosis factor α [TNFα]) on the vasomotor responses of resistance arteries. Isolated small mesenteric...... arteries from 3-month-old Sprague-Dawley rats, were suspended for 21-23 h in tissue cultures containing either elevated Glc (30 mmol/l), Ins (100 nmol/l), TNFα (100 ng/ml) or combinations thereof. After incubation, the vascular response to noradrenaline (NA), phenylephrine, isoprenaline and NA...... in vascular tone....

  10. Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

    Rodeghiero, F; Castaman, G C; Dal Belin Peruffo, A; Dini, E; Galletti, A; Barone, E; Gastaldi, G

    1987-06-03

    Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.

  11. Oxidative Metabolism Genes Are Not Responsive to Oxidative Stress in Rodent Beta Cell Lines

    Faer Morrison

    2012-01-01

    Full Text Available Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L, ambient (11 mmol/L, and high (28 mmol/L glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS production was evident in INS-1 cells after 48 hours (P<0.05. TLDA analysis revealed a significant (P<0.05 upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells.

  12. Seaweed supplements normalise metabolic, cardiovascular and liver responses in high-carbohydrate, high-fat fed rats.

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C; Paul, Nicholas A; Brown, Lindsay

    2015-02-02

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330-340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

  13. Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

    Senthil Arun Kumar

    2015-02-01

    Full Text Available Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO and Derbesia tenuissima (DT, in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

  14. Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C.; Paul, Nicholas A.; Brown, Lindsay

    2015-01-01

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium. PMID:25648511

  15. Cardiovascular, respiratory and metabolic responses to temperature and hypoxia of the winter frog Rana catesbeiana

    Rocha P.L.

    1997-01-01

    Full Text Available The objective of the present study was to determine the effects of hypoxia and temperature on the cardiovascular and respiratory systems and plasma glucose levels of the winter bullfrog Rana catesbeiana. Body temperature was maintained at 10, 15, 25 and 35oC for measurements of breathing frequency, heart rate, arterial blood pressure, metabolic rate, plasma glucose levels, blood gases and acid-base status. Reducing body temperature from 35 to 10oC decreased (P<0.001 heart rate (bpm from 64.0 ± 3.1 (N = 5 to 12.5 ± 2.5 (N = 6 and blood pressure (mmHg (P<0.05 from 41.9 ± 2.1 (N = 5 to 33.1 ± 2.1 (N = 6, whereas no significant changes were observed under hypoxia. Hypoxia-induced changes in breathing frequency and acid-base status were proportional to body temperature, being pronounced at 25oC, less so at 15oC, and absent at 10oC. Hypoxia at 35oC was lethal. Under normoxia, plasma glucose concentration (mg/dl decreased (P<0.01 from 53.0 ± 3.4 (N = 6 to 35.9 ± 1.7 (N = 6 at body temperatures of 35 and 10oC, respectively. Hypoxia had no significant effect on plasma glucose concentration at 10 and 15oC, but at 25oC there was a significant increase under conditions of 3% inspired O2. The arterial PO2 and pH values were similar to those reported in previous studies on non-estivating Rana catesbeiana, but PaCO2 (37.5 ± 1.9 mmHg, N = 5 was 3-fold higher, indicating increased plasma bicarbonate levels. The estivating bullfrog may be exposed not only to low temperatures but also to hypoxia. These animals show temperature-dependent responses that may be beneficial since during low body temperatures the sensitivity of most physiological systems to hypoxia is reduced

  16. Ionomic and metabolic responses to neutral salt or alkaline salt stresses in maize (Zea mays L.) seedlings.

    Guo, Rui; Shi, LianXuan; Yan, Changrong; Zhong, Xiuli; Gu, FengXue; Liu, Qi; Xia, Xu; Li, Haoru

    2017-02-10

    Soil salinity and alkalinity present a serious threat to global agriculture. However, most of the studies have focused on neutral salt stress, and the information on the metabolic responses of plants to alkaline salt stress is limited. This investigation aimed at determining the influence of neutral salt and alkaline salt stresses on the content of metal elements and metabolites in maize plant tissues, by using mixtures of various proportions of NaCl, NaHCO 3 , Na 2 SO 4 , and Na 2 CO 3 . We found that alkaline salt stress suppressed more pronouncedly the photosynthesis and growth of maize plants than salinity stress. Under alkaline salt stress conditions, metal ions formed massive precipitates, which ultimately reduced plant nutrient availability. On the other hand, high neutral salt stress induced metabolic changes in the direction of gluconeogenesis leading to the enhanced formation of sugars as a reaction contributing to the mitigation of osmotic stress. Thus, the active synthesis of sugars in shoots was essential to the development of salt tolerance. However, the alkaline salt stress conditions characterized by elevated pH values suppressed substantially the levels of photosynthesis, N metabolism, glycolysis, and the production of sugars and amino acids. These results indicate the presence of different defensive mechanisms responsible for the plant responses to neutral salt and alkaline salt stresses. In addition, the increased concentration of organic acids and enhanced metabolic energy might be potential major factors that can contribute to the maintenance intracellular ion balance in maize plants and counteract the negative effects of high pH under alkaline salt stress.

  17. Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.

    Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2015-12-01

    There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.

  18. Heat dissipation does not suppress an immune response in laboratory mice divergently selected for basal metabolic rate (BMR).

    Książek, Aneta; Konarzewski, Marek

    2016-05-15

    The capacity for heat dissipation is considered to be one of the most important constraints on rates of energy expenditure in mammals. To date, the significance of this constraint has been tested exclusively under peak metabolic demands, such as during lactation. Here, we used a different set of metabolic stressors, which do not induce maximum energy expenditures and yet are likely to expose the potential constraining effect of heat dissipation. We compared the physiological responses of mice divergently selected for high (H-BMR) and low basal metabolic rate (L-BMR) to simultaneous exposure to the keyhole limpet haemocyanin (KLH) antigen and high ambient temperature (Ta). At 34°C (and at 23°C, used as a control), KLH challenge resulted in a transient increase in core body temperature (Tb) in mice of both line types (by approximately 0.4°C). Warm exposure did not produce line-type-dependent differences in Tb (which was consistently higher by ca. 0.6°C in H-BMR mice across both Ta values), nor did it result in the suppression of antibody synthesis. These findings were also supported by the lack of between-line-type differences in the mass of the thymus, spleen or lymph nodes. Warm exposure induced the downsizing of heat-generating internal organs (small intestine, liver and kidneys) and an increase in intrascapular brown adipose tissue mass. However, these changes were similar in scope in both line types. Mounting a humoral immune response in selected mice was therefore not affected by ambient temperature. Thus, a combined metabolic challenge of high Ta and an immune response did not appreciably compromise the capacity to dissipate heat, even in the H-BMR mice. © 2016. Published by The Company of Biologists Ltd.

  19. Transcriptome Analysis Identifies Key Metabolic Changes in the Hooded Seal (Cystophora cristata Brain in Response to Hypoxia and Reoxygenation.

    Mariana Leivas Müller Hoff

    Full Text Available The brain of diving mammals tolerates low oxygen conditions better than the brain of most terrestrial mammals. Previously, it has been demonstrated that the neurons in brain slices of the hooded seal (Cystophora cristata withstand hypoxia longer than those of mouse, and also tolerate reduced glucose supply and high lactate concentrations. This tolerance appears to be accompanied by a shift in the oxidative energy metabolism to the astrocytes in the seal while in terrestrial mammals the aerobic energy production mainly takes place in neurons. Here, we used RNA-Seq to compare the effect of hypoxia and reoxygenation in vitro on brain slices from the visual cortex of hooded seals. We saw no general reduction of gene expression, suggesting that the response to hypoxia and reoxygenation is an actively regulated process. The treatments caused the preferential upregulation of genes related to inflammation, as found before e.g. in stroke studies using mammalian models. Gene ontology and KEGG pathway analyses showed a downregulation of genes involved in ion transport and other neuronal processes, indicative for a neuronal shutdown in response to a shortage of O2 supply. These differences may be interpreted in terms of an energy saving strategy in the seal's brain. We specifically analyzed the regulation of genes involved in energy metabolism. Hypoxia and reoxygenation caused a similar response, with upregulation of genes involved in glucose metabolism and downregulation of the components of the pyruvate dehydrogenase complex. We also observed upregulation of the monocarboxylate transporter Mct4, suggesting increased lactate efflux. Together, these data indicate that the seal brain responds to the hypoxic challenge by a relative increase in the anaerobic energy metabolism.

  20. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    Kim, Young C.; Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

    2007-01-01

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

  1. Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel.

    Mathilde Bayet-Robert

    Full Text Available BACKGROUND: Curcumin (CUR has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated. METHODOLOGY/PRINCIPAL FINDINGS: (1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX. In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx increased at low dose CUR (≤ 10 mg.l(-1-28 µM- (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01, but decreased at high dose (≥ 25 mg.l(-1 -70 µM- (-49%, in MCF7 cells, P<0.02, and -56% in MDA-MB-231 cells, P<0.025. At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (-60 to -80%, all, P<0.05. Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025, and decrease of glycerophospho-ethanolamine and -choline (about -60%, P<0.025. Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l(-1 in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR. CONCLUSIONS/SIGNIFICANCE: Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted

  2. Differential metabolic responses in three life stages of mussels Mytilus galloprovincialis exposed to cadmium.

    Wu, Huifeng; Xu, Lanlan; Yu, Deliang; Ji, Chenglong

    2017-01-01

    Cadmium (Cd) is one of the most important metal contaminants in the Bohai Sea. In this work, NMR-based metabolomics was used to investigate the toxicological effects of Cd at an environmentally relevant concentration (50 µg L -1 ) in three different life stages (D-shape larval, juvenile and adult) of mussels Mytilus galloprovincialis. Results indicated that the D-shape larval mussel was the most sensitive life stage to Cd. The significantly different metabolic profiles meant that Cd induced differential toxicological effects in three life stages of mussels. Basically, Cd caused osmotic stress in all the three life stages via different metabolic pathways. Cd exposure reduced the anaerobiosis in D-shape larval mussels and disturbed lipid metabolism in juvenile mussels, respectively. Compared with the D-shape larval and juvenile mussels, the adult mussels reduced energy consumption to deal with Cd stress.

  3. Contribution to the study of plasmatic fibrinogen and serum albumin: effects of irradiation; Contribution a l'etude du fibrinogene et de la serum-albumine plasmatiques - effets de l'irradiation

    Suscillon, M [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Grenoble, 38 (France)

    1967-07-01

    The author studies the modifications of properties and structure of serum albumin and fibrinogen solution when subjected to radiation of low energy (X rays). On the other hand, two original techniques are exposed: 1. Amperometric determination of fibrin stabilizing factor or factor XIII of hemostasis. 2. Spectrophotometric study of fibrin formation kinetics. Then showing off and quantitative determination of platelets fibrinogen is exposed. (author) [French] L'auteur etudie les modifications des proprietes et de la structure des molecules de serum-albumine et de fibrinogene en solution soumise a un flux de RX de basse energie. D'autre part deux techniques originales sont exposees : 1. Dosage amperometrique du facteur stabilisant de la fibrine. 2. Etude spectrophotometrique de la cinetique de la fibro-formation. Enfin une mise en evidence et un dosage du fibrinogene plaquettaire sont presentes. (auteur)

  4. Contribution to the study of plasmatic fibrinogen and serum albumin: effects of irradiation; Contribution a l'etude du fibrinogene et de la serum-albumine plasmatiques - effets de l'irradiation

    Suscillon, M. [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Grenoble, 38 (France)

    1967-07-01

    The author studies the modifications of properties and structure of serum albumin and fibrinogen solution when subjected to radiation of low energy (X rays). On the other hand, two original techniques are exposed: 1. Amperometric determination of fibrin stabilizing factor or factor XIII of hemostasis. 2. Spectrophotometric study of fibrin formation kinetics. Then showing off and quantitative determination of platelets fibrinogen is exposed. (author) [French] L'auteur etudie les modifications des proprietes et de la structure des molecules de serum-albumine et de fibrinogene en solution soumise a un flux de RX de basse energie. D'autre part deux techniques originales sont exposees : 1. Dosage amperometrique du facteur stabilisant de la fibrine. 2. Etude spectrophotometrique de la cinetique de la fibro-formation. Enfin une mise en evidence et un dosage du fibrinogene plaquettaire sont presentes. (auteur)

  5. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.

    1996-01-01

    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  6. Physiological response to extreme fasting in subantarctic fur seal (Arctocephalus tropicalis) pups: metabolic rates, energy reserve utilization, and water fluxes.

    Verrier, Delphine; Groscolas, René; Guinet, Christophe; Arnould, John P Y

    2009-11-01

    Surviving prolonged fasting requires various metabolic adaptations, such as energy and protein sparing, notably when animals are simultaneously engaged in energy-demanding processes such as growth. Due to the intermittent pattern of maternal attendance, subantarctic fur seal pups have to repeatedly endure exceptionally long fasting episodes throughout the 10-mo rearing period while preparing for nutritional independence. Their metabolic responses to natural prolonged fasting (33.4 +/- 3.3 days) were investigated at 7 mo of age. Within 4-6 fasting days, pups shifted into a stage of metabolic economy characterized by a minimal rate of body mass loss (0.7%/day) and decreased resting metabolic rate (5.9 +/- 0.1 ml O(2)xkg(-1)xday(-1)) that was only 10% above the level predicted for adult terrestrial mammals. Field metabolic rate (289 +/- 10 kJxkg(-1)xday(-1)) and water influx (7.9 +/- 0.9 mlxkg(-1)xday(-1)) were also among the lowest reported for any young otariid, suggesting minimized energy allocation to behavioral activity and thermoregulation. Furthermore, lean tissue degradation was dramatically reduced. High initial adiposity (>48%) and predominant reliance on lipid catabolism likely contributed to the exceptional degree of protein sparing attained. Blood chemistry supported these findings and suggested utilization of alternative fuels, such as beta-hydroxybutyrate and de novo synthesized glucose from fat-released glycerol. Regardless of sex and body condition, pups tended to adopt a convergent strategy of extreme energy and lean body mass conservation that appears highly adaptive for it allows some tissue growth during the repeated episodes of prolonged fasting they experience throughout their development.

  7. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A.; Alaee, Mehran; Simpson, Andre J.; Simpson, Myrna J.

    2011-01-01

    Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: → NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. → Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. → NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - 1 H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  8. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

    2011-12-15

    Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  9. METABOLIC AND HORMONAL RESPONSES TO ADRENOCEPTOR ANTAGONISTS IN 48-HOUR-STARVED EXERCISING RATS

    BENTHEM, L; VANDERLEEST, J; STEFFENS, AB; ZIJLSTRA, WG

    1995-01-01

    The influence of 48 hours of starvation on sympathoadrenal regulation of nutrient utilization was investigated in rats. To assess the role of alpha- and beta-adrenoceptors, rats were studied during alpha- and beta-blockade. Energy metabolism was measured using indirect calorimetry before, during,

  10. Type I Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome

    Ghazarian, Magar; Revelo, Xavier S; Nøhr, Mark K

    2017-01-01

    Obesity-related insulin resistance is driven by low-grade chronic inflammation of metabolic tissues. In the liver, non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and systemic glucose dysregulation. However, the immunological factors supporting these proces...

  11. LXR signaling couples sterol metabolism to proliferation in the acquired immune response

    Bensinger, Steven J.; Bradley, Michelle N.; Joseph, Sean B.; Zelcer, Noam; Janssen, Edith M.; Hausner, Mary Ann; Shih, Roger; Parks, John S.; Edwards, Peter A.; Jamieson, Beth D.; Tontonoz, Peter

    2008-01-01

    Cholesterol is essential for membrane synthesis; however, the mechanisms that link cellular lipid metabolism to proliferation are incompletely understood. We demonstrate here that cellular cholesterol levels in dividing T cells are maintained in part through reciprocal regulation of the LXR and

  12. Metabolic state defines the response of rabbit ovarian cells to leptin

    Harrath, Abdel Halim; Østrup, Olga; Rafay, Jan

    2017-01-01

    Leptin is a hormone that mediates the effect of the metabolic state on several biological functions, including reproduction. Leptin affects reproductive functions via alterations in the release of hormonal regulators. However, the extent to which caloric restriction (CR) can affect the complex...

  13. Blood flow and glucose metabolism in stage IV breast cancer: Heterogeneity of response during chemotherapy

    N.C. Krak (Nanda); J. van der Hoeven (John); O.S. Hoekstra (Otto); J.W.R. Twisk (Jos); E.E. van der Wall (Ernst); A.A. Lammertsma (Adriaan)

    2008-01-01

    textabstractObjective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone

  14. Exercise training and work task induced metabolic and stress-related mRNA and protein responses in myalgic muscles

    Sjøgaard, Gisela; Zebis, Mette Kreutzfeldt; Kiilerich, Kristian

    2013-01-01

    healthy controls. Those with myalgia performed similar to 7 hrs repetitive stressful work and were subsequently randomized to 10 weeks of specific strength training, general fitness training, or reference intervention. Muscles biopsies were taken from the trapezius muscle at baseline, after work and after...... 10 weeks intervention. The main findings are that the capacity of carbohydrate oxidation was reduced in myalgic compared with healthy muscle. Repetitive stressful work increased mRNA content for heat shock proteins and decreased levels of key regulators for growth and oxidative metabolism......The aim was to assess mRNA and/or protein levels of heat shock proteins, cytokines, growth regulating, and metabolic proteins in myalgic muscle at rest and in response to work tasks and prolonged exercise training. A randomized controlled trial included 28 females with trapezius myalgia and 16...

  15. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  16. Ex vivo addition of fibrinogen concentrate improves the fibrin network structure in plasma samples taken during liver transplantation

    Groeneveld, D. J.; Adelmeijer, J.; Hugenholtz, G. C. G.; Ariens, R. A. S.; Porte, R. J.; Lisman, T.

    2015-01-01

    Background: Optimal hemostatic management during orthotopic liver transplantation (OLT) remains a challenge. The cause of bleeding during OLT is multifactorial, and may include hemostatic imbalance. Fibrinogen concentrates are increasingly being used to control perioperative bleeding during OLT.

  17. Metabolic response of Pseudomonas putida during redox biocatalysis in the presence of a second octanol phase.

    Blank, Lars M; Ionidis, Georgios; Ebert, Birgitta E; Bühler, Bruno; Schmid, Andreas

    2008-10-01

    A key limitation of whole-cell redox biocatalysis for the production of valuable, specifically functionalized products is substrate/product toxicity, which can potentially be overcome by using solvent-tolerant micro-organisms. To investigate the inter-relationship of solvent tolerance and energy-dependent biocatalysis, we established a model system for biocatalysis in the presence of toxic low logP(ow) solvents: recombinant solvent-tolerant Pseudomonas putida DOT-T1E catalyzing the stereospecific epoxidation of styrene in an aqueous/octanol two-liquid phase reaction medium. Using (13)C tracer based metabolic flux analysis, we investigated the central carbon and energy metabolism and quantified the NAD(P)H regeneration rate in the presence of toxic solvents and during redox biocatalysis, which both drastically increased the energy demands of solvent-tolerant P. putida. According to the driven by demand concept, the NAD(P)H regeneration rate was increased up to eightfold by two mechanisms: (a) an increase in glucose uptake rate without secretion of metabolic side products, and (b) reduced biomass formation. However, in the presence of octanol, only approximately 1% of the maximally observed NAD(P)H regeneration rate could be exploited for styrene epoxidation, of which the rate was more than threefold lower compared with operation with a non-toxic solvent. This points to a high energy and redox cofactor demand for cell maintenance, which limits redox biocatalysis in the presence of octanol. An estimated upper bound for the NAD(P)H regeneration rate available for biocatalysis suggests that cofactor availability does not limit redox biocatalysis under optimized conditions, for example, in the absence of toxic solvent, and illustrates the high metabolic capacity of solvent-tolerant P. putida. This study shows that solvent-tolerant P. putida have the remarkable ability to compensate for high energy demands by boosting their energy metabolism to levels up to an order of

  18. Comparative metabolic responses and adaptive strategies of wheat (Triticum aestivum) to salt and alkali stress.

    Guo, Rui; Yang, Zongze; Li, Feng; Yan, Changrong; Zhong, Xiuli; Liu, Qi; Xia, Xu; Li, Haoru; Zhao, Long

    2015-07-07

    It is well known that salinization (high-pH) has been considered as a major environmental threat to agricultural systems. The aim of this study was to investigate the differences between salt stress and alkali stress in metabolic profiles and nutrient accumulation of wheat; these parameters were also evaluated to determine the physiological adaptive mechanisms by which wheat tolerates alkali stress. The harmful effect of alkali stress on the growth and photosynthesis of wheat were stronger than those of salt stress. High-pH of alkali stress induced the most of phosphate and metal ions to precipitate; as a result, the availability of nutrients significantly declined. Under alkali stress, Ca sharply increased in roots, however, it decreased under salt stress. In addition, we detected the 75 metabolites that were different among the treatments according to GC-MS analysis, including organic acids, amino acids, sugars/polyols and others. The metabolic data showed salt stress and alkali stress caused different metabolic shifts; alkali stress has a stronger injurious effect on the distribution and accumulation of metabolites than salt stress. These outcomes correspond to specific detrimental effects of a highly pH environment. Ca had a significant positive correlation with alkali tolerates, and increasing Ca concentration can immediately trigger SOS Na exclusion system and reduce the Na injury. Salt stress caused metabolic shifts toward gluconeogenesis with increased sugars to avoid osmotic stress; energy in roots and active synthesis in leaves were needed by wheat to develop salt tolerance. Alkali stress (at high pH) significantly inhibited photosynthetic rate; thus, sugar production was reduced, N metabolism was limited, amino acid production was reduced, and glycolysis was inhibited.

  19. Fibrinogen measurements in plasma and whole blood: a performance evaluation study of the dry-hematology system.

    Ogawa, Satoru; Tanaka, Kenichi A; Nakajima, Yasufumi; Nakayama, Yoshinobu; Takeshita, Jun; Arai, Masatoshi; Mizobe, Toshiki

    2015-01-01

    An accurate and rapid determination of fibrinogen level is important during hemorrhage to establish a timely hemostatic intervention. The accuracy of fibrinogen measurements may be affected by the specific methodology for its determination, fluid therapies, and anticoagulant agents. The dry-hematology method (DRIHEMATO®) is a novel approach to determine fibrinogen levels in plasma and whole blood based on thrombin-activated coagulation time. We hypothesized that plasma or whole blood fibrinogen level using the dry-hematology method would be similar to those measured with conventional plasma fibrinogen assays. Acquired hypofibrinogenemia was modeled by serial dilutions of blood samples obtained from 12 healthy volunteers. Citrated whole blood samples were diluted with either normal saline, 5% human albumin, or 6% hydroxyethyl starch to achieve 25%, 50%, and 75% volume replacement. The dry-hematology method, the Clauss method, the prothrombin time (PT)-derived method, determination of antigen levels, and thromboelastometric fibrin formation were compared in plasma or whole blood samples. The effect of heparin on each assay was examined (0 to 6 IU/mL). Comparisons of dry-hematology and other methods were also conducted using ex vivo samples obtained from cardiac surgical patients (n = 60). In plasma samples, there were no significant differences between dry-hematology and the Clauss method, while dry-hematology showed lower fibrinogen levels compared with PT-derived and antigen level methods. The dry-hematology method yielded acceptable concordance correlation coefficients (Pc) with the Clauss method, the PT-derived method, and fibrinogen antigen levels (Pc = 0.91-0.99). The type of diluents and heparin affected the results of the PT-derived method and thromboelastometric assay, but not the dry-hematology method. In cardiac surgical patients, the overall correlation in fibrinogen levels between dry-hematology and the other methods was comparable to the results from

  20. Incorporation of vitronectin into fibrin clots. Evidence for a binding interaction between vitronectin and gamma A/gamma' fibrinogen.

    Podor, Thomas J; Campbell, Stephanie; Chindemi, Paul; Foulon, Denise M; Farrell, David H; Walton, Philip D; Weitz, Jeffrey I; Peterson, Cynthia B

    2002-03-01

    Vitronectin is an abundant plasma protein that regulates coagulation, fibrinolysis, complement activation, and cell adhesion. Recently, we demonstrated that plasma vitronectin inhibits fibrinolysis by mediating the interaction of type 1 plasminogen activator inhibitor with fibrin (Podor, T. J., Peterson, C. B., Lawrence, D. A., Stefansson, S., Shaughnessy, S. G., Foulon, D. M., Butcher, M., and Weitz, J. I. (2000) J. Biol. Chem. 275, 19788-19794). The current studies were undertaken to further examine the interactions between vitronectin and fibrin(ogen). Comparison of vitronectin levels in plasma with those in serum indicates that approximately 20% of plasma vitronectin is incorporated into the clot. When the time course of biotinylated-vitronectin incorporation into clots formed from (125)I-fibrinogen is monitored, vitronectin incorporation into the clot parallels that of fibrinogen in the absence or presence of activated factor XIII. Vitronectin binds specifically to fibrin matrices with an estimated K(d) of approximately 0.6 microm. Additional vitronectin subunits are assembled on fibrin-bound vitronectin multimers through self-association. Confocal microscopy of fibrin clots reveals the globular vitronectin aggregates anchored at intervals along the fibrin fibrils. This periodicity raised the possibility that vitronectin interacts with the gamma A/gamma' variant of fibrin(ogen) that represents about 10% of total fibrinogen. In support of this concept, the vitronectin which contaminates fibrinogen preparations co-purifies with the gamma A/gamma' fibrinogen fraction, and clots formed from gamma A/gamma' fibrinogen preferentially bind vitronectin. These studies reveal that vitronectin associates with fibrin during coagulation, and may thereby modulate hemostasis and inflammation.

  1. Clinical study of 67Ga labelled human fibrinogen for detection of thrombi

    Katsuura, Yutaka

    1988-01-01

    The usefulness to detect thrombi by Ga-67 labelled human fibrinogen (Ga-F) was investigated in 22 patients with various diseases who had thrombi or were suspected to have thrombi. In 5 of 9 patients with aortic aneurysm, images of thrombi were obtained by Ga-F. In 1 of 2 patients with myocardial infarction, left ventricular thrombi were detected. In 1 of 5 patients with mitral stenosis, left atrial thrombus was recognized. Of these patients, in 2 patients who have no evidence of thrombi confirmed at another methods, thrombi were detected by Ga-F. In 6 out of 8 patients with thrombi confirmed at echocardiography or computed tomography, thrombi were detected by Ga-F. In these patients, 2 patients with negative images were treated by antithromboticdrugs. In 7 patients, both Ga-F and In-111 labelled platelets (In-P) were comparatively studied simultaniuosly. No difference in the sensitivity of the detection of thrombi were recognized between two groups. The images of thrombi by both Ga-F and In-P were detected positively in 3 patients and were not found in 4 patients. However, the handling of Ga-F method was much easier than that of In-P method. In conclusion, Ga-F could be useful for the detection of thrombi in various thrombotic diseases. Fibrinogen kinetic studies using Ga-F were performed. Fibrinogen turnover rates (FTR) in the cases with positive image by Ga-F were higher than those in the cases with Ga-F negative image. (positive : 24.3 ± 9.5 mg/kg/day, negative : 19.7 ± 8.5 mg/kg/day) The results of kinetic studies by Ga-F were similar to those by 1 - 125 fibrinogen. (author)

  2. Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein

    Dorota Rowczenio

    2017-05-01

    Discussion: We report 6 novel mutations in the FGA gene: 5 were associated with renal fibrinogen A alpha chain amyloidosis and 1 was found to be incidental to light-chain amyloid deposits discovered in a patient with a plasma cell dyscrasia. Clinical awareness and suspicion of hereditary amyloidosis corroborated by genetic analysis and adequate typing using combined immunohistochemistry and laser microdissection and mass spectrometry is valuable to avoid misdiagnosis, especially when a family history of amyloidosis is absent.

  3. is fibrinogen a reliable haemostatic marker for monitoring possible

    cistvr

    One of the most common adverse effects of smoking is atherosclerosis. This refers to the focal thickening of the arterial wall so that the artery becomes partially or completely occluded. This phenomenon has been reported to be the mechanism mainly responsible for cardiovascular diseases in smokers (Cawley, 1983).

  4. Comparison of PET metabolic indices for the early assessment of tumour response in metastatic colorectal cancer patients treated by polychemotherapy

    Maisonobe, Jacques-Antoine; Necib, Hatem; Buvat, Irene [IMNC UMR 8165 CNRS - Paris 7 and Paris 11 Universities, Orsay Cedex (France); Garcia, Camilo A.; Vanderlinden, Bruno; Flamen, Patrick [Universite Libre de Bruxelles, Department of Nuclear Medicine, Institut Jules Bordet, Brussels (Belgium); Hendlisz, Alain [Universite Libre de Bruxelles, Department of Gastroenterology, Institut Jules Bordet, Brussels (Belgium)

    2013-02-15

    To compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. Forty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for PVE, a metabolic volume (MV) and a total lesion glycolysis (TLG). The relative change in each index between the two scans was calculated for each lesion. Lesions were also classified as responding and nonresponding lesions using the Response Evaluation Criteria In Solid Tumours (RECIST) 1.0 measured by contrast-enhanced CT at baseline and 6-8 weeks after starting therapy. Bland-Altman analyses were performed to compare the various indices. Based on the RECIST classification, ROC analyses were used to determine how accurately the indices predicted lesion response to therapy later seen with RECIST. RECIST showed 27 responding and 74 nonresponding lesions. Bland-Altman analyses showed that the four SUV indices uncorrected for PVE could not be used interchangeably, nor could the two SUV corrected for PVE. The areas under the ROC curves (AUC) were not significantly different between the SUV indices not corrected for PVE. The mean SUV change in a lesion better predicted lesion response without than with PVE correction. The AUC was significantly higher for SUV uncorrected for PVE than for the MV, but change in MV provided some information regarding the lesion response to therapy (AUC >0.5). In these mCRC patients, all SUV uncorrected for PVE accurately predicted the tumour response on day 14 after starting therapy as assessed 4 to 6 weeks later (i.e. 6 to 8 weeks after therapy initiation) using the RECIST criteria. Neither correcting SUV for PVE nor measuring TLG improved the assessment of tumour

  5. Genetic ancestry in relation to the metabolic response to a U.S. versus traditional Mexican diet: a randomized crossover feeding trial among women of Mexican descent

    Santiago-Torres, Margarita; De Dieu Tapsoba, Jean; Kratz, Mario; Lampe, Johanna W.; Breymeyer, Kara L.; Levy, Lisa; Song, Xiaoling; Villase?or, Adriana; Wang, Ching-Yun; Fejerman, Laura; Neuhouser, Marian L.; Carlson, Christopher S.

    2016-01-01

    Background Certain populations with a large proportion of Indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to U.S. diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a U.S. versus traditional Mexican diet in a controlled dietary intervention. Methods First and second generation Mexican immigrant...

  6. Evaluation of in vivo stability of Ga-67 labeled human fibrinogen

    Takahashi, Keietsu; Takahashi, Jun; Okano, Sakae; Kurami, Miki; Ueda, Nobuo; Hazue, Masaaki

    1987-01-01

    Human fibrinogen (Fib) was conjugated with a large number of deferoxamine (DFO) through dialdehyde starch (DAS), and the conjugate (Fib-DAS-DFO) was labeled with Ga-67. Thus labeled fibrinogen (Ga-67-Fib-DAS-DFO) showed a high labeling efficiency (more than 90 %) and retained clottability (more than 80 %). For the evaluation of plasma radioactive species, blood samples were collected at various time periods after the i.v. administration of Ga-67-Fib-DAS-DFO into rats, and the plasma radioactivity was analyzed by high performance liquid chromatography (HPLC) and electrophoresis (EP). The radioactive HPLC elution profiles for the plasma samples were identical with that of the original Ga-67-Fib-DAS-DFO; the EP patterns for the plasma were also identical with the original one, and no radioactive species, except for Ga-67-Fib-DAS-DFO, was detected by HPLC or EP. Furthermore, the presence of transferrin in the labeling formulation did not affect the labeling yield of Ga-67-Fib-DAS-DFO indicating that the transchelation of Ga-67 from DFO on Fib to transferrin is negligible. These findings indicated that Ga-67 is tightly bound to Fib-DAS-DFO in blood, and the Ga-67-Fib-DAS-DFO can be efficiently trapped by clots as the result of its high retention of physiological activities as fibrinogen. (author)

  7. Quantitative Proteomic Approach Targeted to Fibrinogen β Chain in Tissue Gastric Carcinoma

    Ombretta Repetto

    2018-03-01

    Full Text Available Elevated plasma fibrinogen levels and tumor progression in patients with gastric cancer (GC have been largely reported. However, distinct fibrinogen chains and domains have different effects on coagulation, inflammation, and angiogenesis. The aim of this study was to characterize fibrinogen β chain (FGB in GC tissues. Retrospectively we analyzed the data of matched pairs of normal (N and malignant tissues (T of 28 consecutive patients with GC at diagnosis by combining one- and two-dimensional electrophoresis (1DE and 2DE with immunoblotting and mass spectrometry together with two-dimensional difference in gel electrophoresis (2D-DIGE. 1DE showed bands of the intact FGB at 50 kDa and the cleaved forms containing the fragment D at ~37–40 kDa, which corresponded to 19 spots in 2DE. In particular, spot 402 at ~50 kDa and spots 526 and 548 at ~37 kDa were of interest by showing an increased expression in tumor tissues. A higher content of spot 402 was associated with stomach antrum, while spots 526 and 548 amounts correlated with corpus and high platelet count (>208 × 109/L. The quantification of FGB and cleaved products may help to further characterize the interconnections between GC and platelet/coagulation pathways.

  8. Familial hypofibrinogenaemia associated with heterozygous substitution of a conserved arginine residue; Bbeta255 Arg-->His (Fibrinogen Merivale).

    Maghzal, Ghassan J; Brennan, Stephen O; Fellowes, Andrew P; Spearing, Ruth; George, Peter M

    2003-02-21

    Sequencing of all three fibrinogen genes from an individual with hypofibrinogenaemia led to the identification of two new point mutations in the Bbeta gene. Family studies showed the mutations Bbeta255 Arg-->His (Fibrinogen Merivale) and Bbeta148 Lys-->Asn (Fibrinogen Merivale II) were on different alleles and that only the Bbeta255 Arg-->His mutation segregated with hypofibrinogenaemia. Three simple heterozygotes for this mutation had mean fibrinogen concentrations of 1.4 mg/ml, while heterozygotes for the Bbeta148 Lys-->Asn mutation had normal fibrinogen concentrations. ESI MS analysis of endoproteinase Asp-N digests of Bbeta chains showed that the Bbeta255 Arg-->His substitution was not expressed in plasma, confirming it as the cause of the hypofibrinogenaemia. The Bbeta148 Lys-->Asn chains, on the other hand, were equally expressed with wild-type Bbeta chains in simple heterozygotes. Genotype analysis failed to detect either substitution in 182 healthy controls. Arg(255) is located in the first strand of the five-stranded sheet that forms the main feature of the betaD domain and appears to form an essential H bond with Gly(414). Both the Arg and Gly are absolutely conserved, not only in all known Bbeta chains, but also in all homologous alphaE and gamma chains and in all fibrinogen-related proteins. Protein instability from loss of this contact could easily explain the association of this mutation with hypofibrinogenaemia.

  9. Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin.

    do Carmo, J M; da Silva, A A; Sessums, P O; Ebaady, S H; Pace, B R; Rushing, J S; Davis, M T; Hall, J E

    2014-06-01

    We examined whether deficiency of Src homology 2 containing phosphatase (Shp2) signaling in forebrain neurons alters metabolic and cardiovascular regulation under various conditions and if it attenuates the anorexic and cardiovascular effects of leptin. We also tested whether forebrain Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute stress. Forebrain Shp2(-/-) mice were generated by crossing Shp2(flox/flox) mice with CamKIIα-cre mice. At 22-24 weeks of age, the mice were instrumented for telemetry for measurement of BP, HR and body temperature (BT). Oxygen consumption (VO2), energy expenditure and motor activity were monitored by indirect calorimetry. Shp2/CamKIIα-cre mice were heavier (46±3 vs 32±1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic and hyperphagic compared to Shp2(flox/flox) control mice. Shp2/CamKIIα-cre mice exhibited reduced food intake responses to fasting/refeeding and impaired regulation of BT when exposed to 15 and 30 °C ambient temperatures. Despite being obese and having many features of metabolic syndrome, Shp2/CamKIIα-cre mice had similar daily average BP and HR compared to Shp2(flox/flox) mice (112±2 vs 113±1 mm Hg and 595±34 vs 650±40 b.p.m.), but exhibited increased BP and HR responses to cold exposure and acute air-jet stress test. Leptin's ability to reduce food intake and to raise BP were markedly attenuated in Shp2/CamKIIα-cre mice. These results suggest that forebrain Shp2 signaling regulates food intake, appetite responses to caloric deprivation and thermogenic control of body temperature during variations in ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated with augmented cardiovascular responses to cold and acute stress but attenuated BP responses to leptin.

  10. Similar metabolic responses to calorie restriction in lean and obese Zucker rats.

    Chiba, Takuya; Komatsu, Toshimitsu; Nakayama, Masahiko; Adachi, Toshiyuki; Tamashiro, Yukari; Hayashi, Hiroko; Yamaza, Haruyoshi; Higami, Yoshikazu; Shimokawa, Isao

    2009-10-15

    Calorie restriction (CR), which is thought to be largely dependent on the neuroendocrine system modulated by insulin/insulin-like growth factor-I (IGF-I) and leptin signaling, decreases morbidity and increases lifespan in many organisms. To elucidate whether insulin and leptin sensitivities are indispensable in the metabolic adaptation to CR, we investigated the effects of CR on obese Zucker (fa/fa) rats and lean control (+/+) rats. CR did not fully improve insulin resistance in (fa/fa) rats. Nonetheless, CR induced neuropeptide Y (NPY) expression in the hypothalamic arcuate nucleus and metabolism related gene expression changes in the liver in (fa/fa) rats and (+/+) rats. Up-regulation of NPY augmented plasma corticosterone levels and suppressed pituitary growth hormone (GH) expression, thereby modulating adipocytokine production to induce tissue-specific insulin sensitivity. Thus, central NPY activation via peripheral signaling might play a crucial role in the effects of CR, even in insulin resistant and leptin receptor deficient conditions.

  11. Dual drug encapsulated thermo-sensitive fibrinogen-graft-poly (N-isopropyl acrylamide) nanogels for breast cancer therapy.

    Rejinold, N Sanoj; Baby, Thejus; Chennazhi, K P; Jayakumar, R

    2014-02-01

    5-FU/Megestrol acetate loaded fibrinogen-graft-PNIPAAm Nanogels (5-FU/Meg-fib-graft-PNIPAAm NGs) were prepared for thermo responsive drug delivery toward α5β1-integrins expressing breast cancer cells in vitro (MCF-7 cells). The 60-100 nm sized fib-graft-PNIPAAm nanogels (LCST=35 °C) were prepared by CaCl2 cross-linker. 5-FU/Meg-fib-graft-PNIPAAm NGs showed particle size of 165-195 nm size. The drug loading efficiency with 5-FU was 60% and 70% for Meg. "Drug release was greater above the lower critical solution temperature (LCST). Above LCST, drug release system triggers apopotosis and enhance toxicity to MCF-7 cells when compared to the equivalent dose of the free drug. This effect was due to the greater uptake of the drug by MCF-7 cells". 5-FU/Meg-fib-graft-PNIPAAm NGs is portrayed here as a new combinatorial thermo-responsive drug delivery agent for breast cancer therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Postprandial nutrient-sensing and metabolic responses after partial dietary fishmeal replacement by soyabean meal in turbot (Scophthalmus maximus L.).

    Xu, Dandan; He, Gen; Mai, Kangsen; Zhou, Huihui; Xu, Wei; Song, Fei

    2016-02-14

    In this study, we chose a carnivorous fish, turbot (Scophthalmus maximus L.), to examine its nutrient-sensing and metabolic responses after ingestion of diets with fishmeal (FM), or 45% of FM replaced by soyabean meal (34·6% dry diet) balanced with or without essential amino acids (EAA) to match the amino acid profile of FM diet for 30 d. After a 1-month feeding trial, fish growth, feed efficiency and nutrient retention were markedly reduced by soyabean meal-incorporated (SMI) diets. Compared with the FM diet, SMI led to a reduction of postprandial influx of free amino acids, hypoactivated target of rapamycin signalling and a hyperactivated amino acid response pathway after refeeding, a status associated with reduced protein synthesis, impaired postprandial glycolysis and lipogenesis. These differential effects were not ameliorated by matching an EAA profile of soyabean meal to that of the FM diet through dietary amino acid supplementation. Therefore, this study demonstrated that the FM diet and SMI diets led to distinct nutrient-sensing responses, which in turn modulated metabolism and determined the utilisation efficiency of diets. Our results provide a new molecular explanation for the role of nutrient sensing in the inferior performance of aquafeeds in which FM is replaced by soyabean meal.

  13. Interrelations between glucose-induced insulin response, metabolic indicators, and time of first ovulation in high-yielding dairy cows.

    Bossaert, P; Leroy, J L M R; De Vliegher, S; Opsomer, G

    2008-09-01

    High-yielding dairy cows are more susceptible to metabolic and reproductive disorders than low-yielding cows. Insulin plays a pivotal role in the development of both problems. In the present study, we aimed to assess the glucose-induced insulin responses of dairy cows at different time points relative to calving and to relate this to the metabolic status and the time of first ovulation. Twenty-three healthy, multiparous Holstein-Friesian cows with a high genetic merit for milk yield were studied from 14 d prepartum to 42 d