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Sample records for kallikrein kinin system

  1. Towards understanding the kallikrein-kinin system: insights from measurement of kinin peptides

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    D.J. Campbell

    2000-06-01

    Full Text Available The kallikrein-kinin system is complex, with several bioactive peptides that are formed in many different compartments. Kinin peptides are implicated in many physiological and pathological processes including the regulation of blood pressure and sodium homeostasis, inflammatory processes, and the cardioprotective effects of preconditioning. We established a methodology for the measurement of individual kinin peptides in order to study the function of the kallikrein-kinin system. The levels of kinin peptides in tissues were higher than in blood, confirming the primary tissue localization of the kallikrein-kinin system. Moreover, the separate measurement of bradykinin and kallidin peptides in man demonstrated the differential regulation of the plasma and tissue kallikrein-kinin systems, respectively. Kinin peptide levels were increased in the heart of rats with myocardial infarction, in tissues of diabetic and spontaneously hypertensive rats, and in urine of patients with interstitial cystitis, suggesting a role for kinin peptides in the pathogenesis of these conditions. By contrast, blood levels of kallidin, but not bradykinin, peptides were suppressed in patients with severe cardiac failure, suggesting that the activity of the tissue kallikrein-kinin system may be suppressed in this condition. Both angiotensin converting enzyme (ACE and neutral endopeptidase (NEP inhibitors increased bradykinin peptide levels. ACE and NEP inhibitors had different effects on kinin peptide levels in blood, urine, and tissues, which may be accounted for by the differential contributions of ACE and NEP to kinin peptide metabolism in the multiple compartments in which kinin peptide generation occurs. Measurement of the levels of individual kinin peptides has given important information about the operation of the kallikrein-kinin system and its role in physiology and disease states.

  2. Lack of plasma kallikrein-kinin system cascade in teleosts.

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    Marty Kwok-Shing Wong

    Full Text Available The kallikrein-kinin system (KKS consists of two major cascades in mammals: "plasma KKS" consisting of high molecular-weight (HMW kininogen (KNG, plasma kallikrein (KLKB1, and bradykinin (BK; and "tissue KKS" consisting of low molecular-weight (LMW KNG, tissue kallikreins (KLKs, and [Lys(0]-BK. Some components of the KKS have been identified in the fishes, but systematic analyses have not been performed, thus this study aims to define the KKS components in teleosts and pave a way for future physiological and evolutionary studies. Through a combination of genomics, molecular, and biochemical methods, we showed that the entire plasma KKS cascade is absent in teleosts. Instead of two KNGs as found in mammals, a single molecular weight KNG was found in various teleosts, which is homologous to the mammalian LMW KNG. Results of molecular phylogenetic and synteny analyses indicated that the all current teleost genomes lack KLKB1, and its unique protein structure, four apple domains and one trypsin domain, could not be identified in any genome or nucleotide databases. We identified some KLK-like proteins in teleost genomes by synteny and conserved domain analyses, which could be the orthologs of tetrapod KLKs. A radioimmunoassay system was established to measure the teleost BK and we found that [Arg(0]-BK is the major circulating form instead of BK, which supports that the teleost KKS is similar to the mammalian tissue KKS. Coincidently, coelacanths are the earliest vertebrate that possess both HMW KNG and KLKB1, which implies that the plasma KKS could have evolved in the early lobe-finned fish and descended to the tetrapod lineage. The co-evolution of HMW KNG and KLKB1 in lobe-finned fish and early tetrapods may mark the emergence of the plasma KKS and a contact activation system in blood coagulation, while teleosts may have retained a single KKS cascade.

  3. Kallikrein-kinin in stem cell therapy

    Institute of Scientific and Technical Information of China (English)

    Julie; Chao; Grant; Bledsoe; Lee; Chao

    2014-01-01

    The tissue kallikrein-kinin system exerts a wide spectrum of biological activities in the cardiovascular, renal and central nervous systems. Tissue kallikrein-kinin modulates the proliferation, viability, mobility and functional activity of certain stem cell populations, namely mesenchymal stem cells(MSCs), endothelial progenitor cells(EPCs), mononuclear cell subsets and neural stem cells. Stimulation of these stem cells by tissue kallikrein-kinin may lead to protection against renal, cardiovascular and neural damage by inhibiting apoptosis, inflammation, fibrosis and oxidative stress and promoting neovascularization. Moreover, MSCs and EPCs genetically modified with tissue kallikrein are resistant to hypoxia- and oxidative stress-induced apoptosis, and offer enhanced protective actions in animal models of heart and kidney injury and hindlimb ischemia. In addition, activation of the plasma kallikrein-kinin system promotes EPC recruitment to the inflamed synovium of arthritic rats. Conversely, cleaved high molecular weight kininogen, a product of plasma kallikrein, reduces the viability and vasculogenic activity of EPCs. Therefore, kallikrein-kinin provides a new approach in enhancing the efficacy of stem cell therapy for human diseases.

  4. Interaction of Bacteroides fragilis and Bacteroides thetaiotaomicron with the kallikrein?kinin system

    OpenAIRE

    Murphy, Elizabeth C; M?rgelin, Matthias; Cooney, Jakki C; Frick, Inga-Maria

    2011-01-01

    Many bacterial pathogens interfere with the contact system (kallikrein?kinin system) in human plasma. Activation of this system has two consequences: cleavage of high-molecular-mass kininogen (HK) resulting in release of the potent proinflammatory peptide bradykinin, and initiation of the intrinsic pathway of coagulation. In this study, two species of the Gram-negative anaerobic commensal organism Bacteroides, namely Bacteroides fragilis and Bacteroides thetaiotaomicron, were found to bind HK...

  5. [Kallikrein-kinin system of blood in patients in the post-infarction period, and its reaction to physical exertion].

    Science.gov (United States)

    Azimova, F I; Nekrasova, A A; Chernova, N A; Nikolaeva, L F

    1983-09-01

    Blood kallikrein-kinin function was assessed in myocardial infarction survivors. Increased blood kinin-forming activity was demonstrated, accompanied with a simultaneous rise in the system's inhibitor level and excessive response to exercise, with slower regaining of the baseline after exercise was discontinued. It is concluded that functional testing of blood kallikrein-kinin status by means of rationed exercise yields more informative data on this system in various groups of postinfarction patients and that the extent of the system's activation depends on systemic circulatory function.

  6. Different activation patterns in the plasma kallikrein-kinin and complement systems during coronary bypass surgery.

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    Kongsgaard, U E; Smith-Erichsen, N; Geiran, O; Amundsen, E; Mollnes, T E; Garred, P

    1989-07-01

    Components of the plasma kallikrein-kinin and complement systems were determined in patients undergoing open heart surgery with cardiopulmonary bypass. Spontaneous kallikrein activity (KK), plasma prekallikrein (PKK), functional kallikrein inhibition capacity (KKI), C3 activation products (C3-act), and the terminal complement complex (TCC) were measured. A marked, transitory increase in KK and a decrease in PKK were found prior to cardiopulmonary bypass just after heparin injection. An additional decline in PKK and KKI during bypass with a return to near control levels in the postoperative period was observed. C3-act increased in all patients during bypass, reaching a peak value at wound closure. The TCC concentration also increased significantly during cardiopulmonary bypass, returned to control levels in the early postoperative period, and then increased again in the late postoperative period. It is concluded that activation of the kallikrein-kinin system started after injection of heparin, prior to cardiopulmonary bypass. Activation of both the initial and the terminal complement cascade, however, started only after onset of cardiopulmonary bypass.

  7. Pharmacologic Targets and Prototype Therapeutics in the Kallikrein-Kinin System: Bradykinin Receptor Agonists or Antagonists

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    J. N. Sharma

    2006-01-01

    Full Text Available The kallikrein-kinin system (KKS is a complex system produced in various organs. This system includes kininogen (precursor for kinin, kallikreins, and pharmacologically active bradykinin (BK, which is considered to be proinflammatory and/or cardioprotective. It is a proinflammatory polypeptide that is involved in many pathological conditions and can cause pain, inflammation, increased vascular permeability, vasodilation, contraction of various smooth muscles, as well as cell proliferation. On the other hand, it has been shown that BK has cardioprotective effects, as all components of KKS are located in the cardiac muscles. Numerous observations have indicated that decreased activity of this system may lead to cardiovascular diseases, such as hypertension, cardiac failure, and myocardial infarction. BK acts on two receptors, B1 and B2, which are linked physiologically through their natural stimuli and their common participation in a variety of inflammatory responses. Recently, numerous BK antagonists have been developed in order to treat several diseases that are due to excessive BK formation. Although BK has many beneficial effects, it has been recognized to have some undesirable effects that can be reversed with BK antagonists. In addition, products of this system have multiple interactions with other important metabolic pathways, such as the renin-angiotensin system.

  8. Is the renal kallikrein-kinin system a factor that modulates hypercalciuria?

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    Armando Luis Negri

    2017-01-01

    Full Text Available Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK. Both proteins are synthesised in the distal tubule and secreted in the tubular fluid. TK stimulates active calcium reabsorption through the bradykinin receptor B2 that compromises TRPV5 activation through the protein kinase C pathway. TK-deficient mice show hypercalciuria of renal origin comparable to that seen in TRPV5 knockout mice. There is a polymorphism with loss of function of the human TK gene R53H (allele H that causes a marked decrease in enzymatic activity. The presence of the allele H seems to be common at least in the Japanese population (24%. These individuals have a tendency to greater calcium and sodium excretion in urine that is more evident during furosemide infusion. Future studies should analyse if manipulating the renal kallikrein-kinin system can correct idiopathic hypercalciuria with drugs other than thiazide diuretics.

  9. Renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension.

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    Katori, Makoto; Majima, Masataka

    2014-01-01

    A large variety of antihypertensive drugs, such as angiotensin converting enzyme inhibitors, diuretics, and others, are prescribed to hypertensive patients, with good control of the condition. In addition, all individuals are generally believed to be salt sensitive and, thus, severe restriction of salt intake is recommended to all. Nevertheless, the physiological defense mechanisms in the kidney against excess salt intake have not been well clarified. The present review article demonstrated that the renal (tissue) kallikrein-kinin system (KKS) is ideally situated within the nephrons of the kidney, where it functions to inhibit the reabsorption of NaCl through the activation of bradykinin (BK)-B2 receptors localized along the epithelial cells of the collecting ducts (CD). Kinins generated in the CD are immediately inactivated by two kidney-specific kinin-inactivating enzymes (kininases), carboxypeptidase Y-like exopeptidase (CPY), and neutral endopeptidase (NEP). Our work demonstrated that ebelactone B and poststatin are selective inhibitors of these kininases. The reduced secretion of the urinary kallikrein is linked to the development of salt-sensitive hypertension, whereas potassium ions and ATP-sensitive potassium channel blockers ameliorate salt-sensitive hypertension by accelerating the release of renal kallikrein. On the other hand, ebelactone B and poststatin prolong the life of kinins in the CD after excess salt intake, thereby leading to the augmentation of natriuresis and diuresis, and the ensuing suppression of salt-sensitive hypertension. In conclusion, accelerators of the renal kallikrein release and selective renal kininase inhibitors are both novel types of antihypertensive agents that may be useful for treatment of salt-sensitive hypertension.

  10. Interaction of Bacteroides fragilis and Bacteroides thetaiotaomicron with the kallikrein-kinin system.

    Science.gov (United States)

    Murphy, Elizabeth C; Mörgelin, Matthias; Cooney, Jakki C; Frick, Inga-Maria

    2011-07-01

    Many bacterial pathogens interfere with the contact system (kallikrein-kinin system) in human plasma. Activation of this system has two consequences: cleavage of high-molecular-mass kininogen (HK) resulting in release of the potent proinflammatory peptide bradykinin, and initiation of the intrinsic pathway of coagulation. In this study, two species of the Gram-negative anaerobic commensal organism Bacteroides, namely Bacteroides fragilis and Bacteroides thetaiotaomicron, were found to bind HK and fibrinogen, the major clotting protein, from human plasma as shown by immunoelectron microscopy and Western blot analysis. In addition, these Bacteroides species were capable of activating the contact system at its surface leading to a significant prolongation of the intrinsic coagulation time and also to the release of bradykinin. Members of the genus Bacteroides have been known to act as opportunistic pathogens outside the gut, with B. fragilis being the most common isolate from clinical infections, such as intra-abdominal abscesses and bacteraemia. The present results thus provide more insight into how Bacteroides species cause infection.

  11. What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

    Institute of Scientific and Technical Information of China (English)

    Maria; da; Graa; Naffah-Mazzacoratti; Telma; Luciana; Furtado; Gouveia; Priscila; Santos; Rodrigues; Simōes; Sandra; Regina; Perosa

    2014-01-01

    The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

  12. Involvement of the renal kallikrein-kinin system in K(+)-induced diuresis and natriuresis in anesthetized rats.

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    Suzuki, T; Katori, M; Fujita, T; Kumagai, Y; Majima, M

    2000-07-07

    Intravenous infusion of a high-K(+) solution (67.5 mM KCl, 67.5 mM NaCl) to anesthetized rats increased urine volume by 47.6% after 60 min, compared with infusion of a Na(+) solution (135 mM NaCl). This treatment also increased urinary excretion of Na(+) by 32.2%, in parallel with an increase in excretion of K(+) or Cl(-). Urinary excretion of kallikrein increased within 60 min after the start of K(+) infusion. A bradykinin B(2) receptor antagonist, 8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-me thylamino ]-2,6-dichlorobenzyloxy]-2-methylquinoline (FR173657; 1.0 mg/kg, i.v. ), inhibited the K(+)-induced diuresis and natriuresis by 41.0% and 26.7%, respectively. These results indicate that K(+) load induces diuresis and natriuresis through the renal kallikrein-kinin system in rats.

  13. Contribution of the Kallikrein/Kinin System to the Mediation of ConA-Induced Inflammatory Ascites.

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    Baintner, Károly

    2016-03-01

    Intraperitoneal administration of concanavalin A (ConA, 25 mg/kg b.w.), a cell-binding plant lectin was used for inducing inflammatory ascites, and potential inhibitors were tested in 1 h and 2.5 h experiments, i.e. still before the major influx of leucocytes. At the end of the experiment the peritoneal fluid was collected and measured. The ConA-induced ascites was significantly (p<0.01) and dose-dependently inhibited by icatibant (HOE-140), a synthetic polypeptide antagonist of bradykinin receptors. Aprotinin, a kallikrein inhibitor protein also had significant (p<0.01), but less marked inhibitory effect. L-NAME, an inhibitor of NO synthesis, and atropine methylnitrate, an anticholinergic compound, were ineffective. It is concluded, that the kallikrein/kinin system contributes to the mediation of the ConA-induced ascites by increasing subperitoneal vascular permeability, independent of the eventual vasodilation produced by NO. It is known, that membrane glycoproteins are aggregated by the tetravalent ConA and the resulting distortion of membrane structure may explain the activation of the labile prekallikrein. Complete inhibition of the ConA-induced ascites could not be achieved by aprotinin or icatibant, which indicates the involvement of additional mediators.

  14. [Role of the kallikrein-kininogen-kinin system in the inflammatory reaction and septic shock].

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    Hulot, M; Ers, P; Damas, J; Adam, A

    1984-01-01

    Kinins, which are vasodilatory, permeability-increasing, pain-producing polypeptides, are formed from inactive precursors: kininogens. Their actions make kinins a particularly powerful potential pro-inflammatory factor. However the absence of specific antagonists has so far made it impossible to ascribe them a definite role in inflammation. Two studies of experimental endotoxemia in burns patients, septicemia and septic shock have demonstrated the following facts: activation occurs of specific ( pKK ) and non-specific (plasminogen-plasmin system) kininogenases , K-HMW and K-LMW levels are significantly decreased. Kininogen consumption corresponds to increased BDK production. This would therefore appear to be one of the humoral factors responsible for haemodynamic changes. Though measurement of kininogen levels is still a painstaking process, the development of chromogenic substrates has made pKK and KK measurement simple and fast. Once they have been validated physico-pathologically in a large number of patients, such assays should take their place among the diagnostic weapons of clinical biology at the disposal of clinicians.

  15. Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system.

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    Shannon L Taylor

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS and hantavirus pulmonary syndrome (HPS are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF. To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS. We show that incubation of factor XII (FXII, prekallikrein (PK, and high molecular weight kininogen (HK plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL and increased liberation of bradykinin (BK. Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS, we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation

  16. C1-inhibitor polymers activate the FXII-dependent kallikrein-kinin system

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Sidelmann, Johannes Jakobsen; Biltoft, Daniel

    2015-01-01

    attacks. HAE is caused by mutations in the C1-inh encoding gene, and we recently demonstrated that some mutations give rise to the presence of polymerized C1-inh in the plasma of HAE patients. METHODS: C1-inh polymers corresponding to the size of polymers observed in vivo were produced using heat...... denaturation and gel filtration. The ability of these polymers to facilitate FXII activation was assessed in vitro in an FXII activation bandshift assay. After spiking of plasma with C1-inh polymers, kallikrein generation was analyzed in a global kallikrein generation method. Prekallikrein consumption...... in the entire Danish HAE cohort was analyzed using an ELISA method. RESULTS: C1-inh polymers mediated FXII activation, and a dose dependent kallikrein generation in plasma spiked with C1-inh polymers. An increased (pre)kallikrein consumption was observed in plasma samples from HAE patients presenting with C1...

  17. Characterization of the Kallikrein-Kinin System Post Chemical Neuronal Injury: An In Vitro Biochemical and Neuroproteomics Assessment.

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    Amaly Nokkari

    Full Text Available Traumatic Brain Injury (TBI is the result of a mechanical impact on the brain provoking mild, moderate or severe symptoms. It is acknowledged that TBI leads to apoptotic and necrotic cell death; however, the exact mechanism by which brain trauma leads to neural injury is not fully elucidated. Some studies have highlighted the pivotal role of the Kallikrein-Kinin System (KKS in brain trauma but the results are still controversial and inconclusive. In this study, we investigated both the expression and the role of Bradykinin 1 and 2 receptors (B1R and B2R, in mediating neuronal injury under chemical neurotoxicity paradigm in PC12 cell lines. The neuronal cell line PC12 was treated with the apoptotic drug Staurosporine (STS to induce cell death. Intracellular calcium release was evaluated by Fluo 4-AM staining and showed that inhibition of the B2R prevented calcium release following STS treatment. Differential analyses utilizing immunofluorescence, Western blot and Real-time Polymerase Chain Reaction revealed an upregulation of both bradykinin receptors occurring at 3h and 12h post-STS treatment, but with a higher induction of B2R compared to B1R. This implies that STS-mediated apoptosis in PC12 cells is mainly conducted through B2R and partly via B1R. Finally, a neuroproteomics approach was conducted to find relevant proteins associated to STS and KKS in PC12 cells. Neuroproteomics results confirmed the presence of an inflammatory response leading to cell death during apoptosis-mediated STS treatment; however, a "survival" capacity was shown following inhibition of B2R coupled with STS treatment. Our data suggest that B2R is a key player in the inflammatory pathway following STS-mediated apoptosis in PC12 cells and its inhibition may represent a potential therapeutic tool in TBI.

  18. The renal kallikrein-kinin system: its role as a safety valve for excess sodium intake, and its attenuation as a possible etiologic factor in salt-sensitive hypertension.

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    Katori, Makoto; Majima, Masataka

    2003-02-01

    The distal tubules of the kidney express the full set of the components of the kallikrein-kinin system, which works independently from the plasma kallikrein-kinin system. Studies on the role of the renal kallikrein-kinin system, using congenitally kininogen-deficient Brown-Norway Katholiek rats and also bradykinin B2 receptor knockout mice, revealed that this system starts to function and to induce natriuresis and diuresis when sodium accumulates in the body as a result of excess sodium intake or aldosterone release, for example, by angiotensin II. Thus, it can be hypothesized that the system works as a safety valve for sodium accumulation. The large numbers of studies on hypertensive animal models and on essential hypertensive patients, particularly those with salt sensitivity, indicate a tendency toward the reduced excretion of urinary kallikrein, although this reduction is modified by potassium intake and impaired renal function. We hypothesize that the reduced excretion of the renal kallikrein may be attributable to a genetic defect of factor(s) in renal kallikrein secretion process and may cause salt-sensitive hypertension after salt intake.

  19. Early phase components of the kallikrein kinin system in hemorrhagic ascitic fluid and plasma in the rat with induced acute pancreatitis.

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    Seung, W P; Feldman, B F

    1985-09-01

    Acute hemorrhagic pancreatitis (AHP) was induced in 43 anesthetized rats by retrograde injection of sodium taurodeoxycholic acid into the common pancreatic biliary duct. At postinjection hours 1, 3, 6, 12, and 18, samples of plasma and hemorrhagic ascitic fluid (HAF) were obtained from rats in which AHP was induced and from rats that were sham operated. Early phase components of the kallikrein kinin system, including kallikrein-like (KK) activity and prekallikrein (PKK) and kallikrein inhibitor (KKI) concentrations, were measured in plasma and HAF samples. In the rats with induced AHP, PKK concentrations were decreased significantly in 18-hour plasma samples (P less than 0.05) and in all HAF samples (P less than 0.001) from 1 to 18 hours after induction of AHP. The KK activity was significantly increased (P less than 0.001) in the 6- and 12-hour plasma samples. In the 1-hour HAF samples, KK activity was increased greater than 10 times over that in the plasma pool of rats and remained increased for 18 hours. The KKI concentrations were markedly decreased in all HAF samples. In the sham-operated group, no significant change was observed. Histopathologic changes included edema, extensive hemorrhage, focal necrosis of many acinar cells around the head of the pancreas, slight inflammatory cell infiltration, vascular thrombosis, and partial lysis of pancreatic ducts. The extent of the changes of PKK, KK, and KKI values in HAF was greater than the extent of those in plasma. Increasing KK activity in plasma and HAF is indicative of bradykinin generation and the participation of this system in local and systemic pathologic change.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Characterization of the kallikrein-kinin system, metalloproteinases, and their tissue inhibitors in the in-stent restenosis after peripheral percutaneous angioplasty.

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    Ribeiro, Maurício S; Dellalibera-Joviliano, Renata; Becari, Christiane; Teixeira, Felipe Roberti; Araujo, Paula Vasconcelos; Piccinato, Carlos E; Campos, Cesar Presto; Evora, Paulo Roberto B; Joviliano, Edwaldo E

    2014-05-01

    The kallikrein-kinin system (KKS) has several direct and indirect effects on cells and cellular mediators involved in the inflammatory process. Studies about inflammation on percutaneous transluminal angioplasty with stent (PTA/stent) to treat peripheral arterial disease (PAD) in humans are scarce. The matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases expressed in various cells and tissues such as fibroblasts, inflammatory cells, and, smooth muscle cells. Changes in the extracellular matrix (ECM) take place in the pathogenesis of many cardiovascular pathologies. MMPs and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are crucial in ECM remodeling in both physiologic and pathologic conditions. The aim of this study was to evaluate the role of the KKS and the MMP metabolism, which are important mediators that may contribute to tissue repair, in the process of arterial restenosis due to intimal hyperplasia in the femoropopliteal segment with the aim of developing new interventions. Thirty-nine consecutive patients were selected (regardless of ethnic group, age, or sex) for revascularization, who underwent PTA/stent of the femoropopliteal segment. Twenty-five patients with the same clinical characteristics who were scheduled for diagnostic angiography but not subjected to PTA/nitinol stent were also selected. The concentrations in blood of total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein was evaluated by the colorimetric method. Tissue kallikrein was evaluated by the spectrophotometric method. The activity of kininase II was measured by fluorometric analysis. Quantification of MMPs was performed by zymography, which is an electrophoresis technique, and TIMPs were measured by enzyme-linked immunosorbent assay. Among the 31 patients who completed the survey, there were 10 cases of angiographically defined restenosis of >50%, and 21 cases without restenosis. There was an

  1. An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies.

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    Graziela S Ceravolo

    Full Text Available The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R contributes to vascular hypertrophy in angiotensin II (ANG II-induced hypertension, through a mechanism involving reactive oxygen species (ROS generation and extracellular signal-regulated kinase (ERK1/2 activation. Male Wistar rats were infused with vehicle (control rats, 400 ng/Kg/min ANG II (ANG II rats or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg(9-Leu(8-bradykinin (ANGII+DAL rats, via osmotic mini-pumps (14 days or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats. After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg 184 ± 5.9 vs 115 ± 2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE: 21.8 ± 2.7 vs 6.0 ± 1.8] and ERK1/2 phosphorylation (% of control: 218.3 ± 29.4 vs 100 ± 0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17 ± 3.1 and ERK1/2 phosphorylation (137 ± 20.7% in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC stimulated with low concentrations (0.1 nM of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM, B1R antagonist (10 µM and Tiron (superoxide anion scavenger, 10 mM. These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth

  2. Association between the kinin-forming system and cardiovascular pathophysiology

    Institute of Scientific and Technical Information of China (English)

    Jagdish Narain Sharma

    2012-01-01

    All the components of the kallikrein-kinin system are located in the cardiac muscle, and its deficiency may lead to cardiac dysfunction. In recent years, numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischaemia, myocardial infarction and left ventricular hypertrophy, have suggested that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular -related diseases. The cardioprotective property of the angiotensin converting enzyme inhibitors is primarily mediated via kinin releasing pathway, which may cause regression of the left ventricular hypertrophy in hypertensive situations. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension, cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders.

  3. The Kallikrein-Kinin-System in Experimental Chagas Disease: A Paradigm to Investigate the Impact of Inflammatory Edema on GPCR-mediated pathways of Host Cell Invasion by Trypanosoma cruzi

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    Julio eScharfstein

    2013-01-01

    Full Text Available Chronic chagasic myocarditis (CCM depends on Trypanosoma cruzi persistence in the myocardium. Studies of the proteolytic mechanisms governing host/parasite balance in peripheral sites of T. cruzi infection revealed that tissue culture trypomastigotes (TCTs elicit inflammatory edema and stimulate protective type-1 effector T cells through the activation of the Kallikrein-Kinin System (KKS. Molecular studies linked the proinflammatory phenotype of Dm28c TCTs to the synergistic activities of tGPI, a lipid anchor that functions as a TLR2 ligand, and cruzipain, a kinin-releasing cysteine protease. Analysis of the dynamics of inflammation revealed that TCTs activate innate sentinel cells via TLR2, releasing CXC chemokines, which in turn evoke neutrophil/CXCR2-dependent extravasation of plasma proteins, including high molecular weight kininogen (HK, in parasite-laden tissues. Further downstream, TCTs process surface bound HK, liberating lysyl-BK (LBK, which then propagates inflammatory edema via signaling of endothelial G-protein-coupled bradykinin B2 receptors (BK2R. Dm28 TCTs take advantage of the transient availability of infection-promoting peptides (e.g., bradykinin and endothelins in inflamed tissues to invade cardiovascular cells via interdependent signaling of BKRs and endothelin receptors (ETRs. Herein we present a space-filling model whereby ceramide-enriched endocytic vesicles generated by the shingomyelinase pathway might incorporate BK2R and ETRs, which then trigger Ca2+-driven responses that optimize the housekeeping mechanism of plasma membrane repair from cell wounding. The hypothesis predicts that the NFB-inducible BKR (BK1R may integrate the multimolecular signaling platforms forged by ceramide rafts, as the chronic myocarditis progresses. Exploited as gateways for parasite invasion, BK2R, BK1R, ETAR, ETBR and other GPCR partners may enable persistent myocardial parasitism in the edematous tissues at expense of adverse cardiac

  4. Cellular and functional aspects of the renal kallikrein system in health and disease.

    Science.gov (United States)

    Vio, C P; Olavarría, V; González, C; Nazal, L; Córdova, M; Balestrini, C

    1998-01-01

    The kallikrein kinin system is a tissue-derived system with potent renal and cardiovascular effects. Within the kidney, the components of the kallikrein kinin system (kallikrein, kininogen, kinins, kininases, kinin receptors and mediators/modulators) originate from or are located in discrete segments of the nephron in highly specialized cells which determine its physiological effects. The kallikrein system acts on the kidney in a paracrine fashion in two anatomical microenvironments where the system regulates glomerular function, renal hemodynamics, and salt and water excretion. Impairment of the renal kallikrein system contributes to the development of hypertension, in particular to the salt-sensitive hypertension, and other pathologies like diabetes. There are several links between the vasodepressor kallikrein system and the vasopressor renin system which are relevant to normal renal function and to the pathophysiology of hypertension and renal diseases. Local induction of kininase II or angiotensin converting enzyme in the kidney could be a novel mechanism contributing to the renal damage in hypertension and other renal diseases. This review evaluates cellular and functional aspects of the renal kallikrein system with emphasis placed on the cellular localization of its components along the nephron, the links to other vasoactive systems, and the contribution of the system to the pathogenesis of hypertension.

  5. The Extreme Anterior Domain Is an Essential Craniofacial Organizer Acting through Kinin-Kallikrein Signaling

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    Laura Jacox

    2014-07-01

    Full Text Available The extreme anterior domain (EAD is a conserved embryonic region that includes the presumptive mouth. We show that the Kinin-Kallikrein pathway is active in the EAD and necessary for craniofacial development in Xenopus and zebrafish. The mouth failed to form and neural crest (NC development and migration was abnormal after loss of function (LOF in the pathway genes kng, encoding Bradykinin (xBdk, carboxypeptidase-N (cpn, which cleaves Bradykinin, and neuronal nitric oxide synthase (nNOS. Consistent with a role for nitric oxide (NO in face formation, endogenous NO levels declined after LOF in pathway genes, but these were restored and a normal face formed after medial implantation of xBdk-beads into LOF embryos. Facial transplants demonstrated that Cpn function from within the EAD is necessary for the migration of first arch cranial NC into the face and for promoting mouth opening. The study identifies the EAD as an essential craniofacial organizer acting through Kinin-Kallikrein signaling.

  6. Rol del sistema kallicreína kinina y su interrelación con sistemas vasoactivos durante la preñez Role of the kallikrein kinin system and its interrelationship with vasoactive systems in pregnancy

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    Elisabet Oddo

    2011-10-01

    systems. It was demonstrated in rats that activation of KKS precedes the installation of glomerular hyperfiltration as aprotinin prevents the increase in glomerular filtration. In addition, individual or associated inhibition of specific kallikrein kinin system effectors, prostaglandins (PGs and nitric oxide (NO, confirm the glomerular filtration rate dependence of KKS during pregnancy. It was also found that the renin-angiotensin system (RAS contributes to glomerular hyperfiltration as this is affected by the administration of RAS blockers. The peak of hyperfiltration maximum inhibition was obtained by the blockade of both systems (KKS and RAS. In addition, strategies used to alter the glomerular hyperfiltration and increased sodium reabsorption during pregnancy, showed abnormalities in the development of the fetus and placenta, fewer offspring, more fetus resorptions and intrauterine growth retardation. KKS inhibitors associated with RAS or nitric oxide blockers showed the greatest impact. As a consequence, it was demonstrated that KKS plays a central role in the adaptation phenomenom that accompanies normal pregnancy. The interplay of KKS with several vasoactive systems, seem to arrange a network involved in the hemodynamic adaptations to allow the proper development of pregnancy and the fetus and placenta.

  7. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Aburto, Andrés [Program of M.Sc., Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Barría, Agustín [School of Biochemistry, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Cárdenas, Areli [Ph.D. Program, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Carpio, Daniel; Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia (Chile); Burgos, Maria E. [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Ardiles, Leopoldo, E-mail: leopoldoardiles@gmail.com [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile)

    2014-10-15

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

  8. Exogenous kallikrein protects against diabetic nephropathy.

    Science.gov (United States)

    Liu, Wenjuan; Yang, Yeping; Liu, Yemei; Lu, Xiaolan; Guo, Shizhe; Wu, Meng; Wang, Meng; Yan, Linling; Wang, Qinghua; Zhao, Xiaolong; Tong, Xian; Hu, Ji; Li, Yiming; Hu, Renming; Stanton, Robert C; Zhang, Zhaoyun

    2016-11-01

    The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.

  9. 激肽释放酶激肽系统活化在三氯乙烯致敏小鼠肾脏损伤中的作用%Role of kallikrein kinin system activation in kidney injury induced by trichloroethylene sensitized mice

    Institute of Scientific and Technical Information of China (English)

    刘敏; 张澄; 杨鹏; 黄建; 臧丹丹; 张家祥; 朱启星

    2016-01-01

    Objective Through testing the expression of complement C3 fragment C3b and iC3b,C5b-9 as well as indexes of KKS before and after using kallikrein-kinin system inhibitor PKSI-527,observing the relevant between KKS and complement system,we preliminary study on the mechanism how KKS works on the renal injury of sensitized mice model induced by trichloroethylene.Methods Female BALB/c mice (6~8 weeks) were randomly divided into blank control group (5),TCE treated group (15),PKSI-527+TCE treated group (15).Mice were sensitized with TCE in the 1,3,7,10 days,the first and the last challenge were on day 17 and 19.24h before every challenge,mice in PKSI-527 +TCE group were treated with intraperitoneal injection of KKSinhibitor PKSI-527 inhibitor (50mg/kg).Mice were killed 72h after the last challenge.The function of kidney in mice were detected and kidney B1R,B2R expression were detected using real-time quantitative PCR,mice kidney complement C3 fragments C3b,iC3b and C5b-9 deposition were also detected by chemoimmunology.Results Compared with blank control group,all indexes expressions in the solvent control group have no significant change.Compared with the solvent control group,BUN、Cr level and B1R、B2R level have an significant increase (P< 0.05) in TCE sensitized group and PKSI-527+TCE sensitized group;There is a sharp decrease in PKSI-527+TCE sensitized group compared to TCE sensitized group (P< 0.05).Conclusion The renal damage in the TCE sensitization mouse model may aggravated by upregulate complement system followed by the activation of kallikrein-kinin system.%目的 观察使用血浆激肽释放酶激肽系统(kallikrein-kinin system,KKS)抑制剂前后,小鼠血浆中补体C3片段C3b,iC3b,C5b-9蛋白沉积与血浆KKS系统指标的相关性,探讨KKS在三氯乙烯(trichloroethylene,TCE)致敏小鼠肾脏损伤中的作用.方法 将雌性BALB/c小鼠(6~8周)随机分为空白对照组(5只)、溶剂对照组(5只)、TCE处理组(15只)、PKSI-527

  10. Activation of the kinin system in the ovary during ovulation: Role of endogenous progesterone

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    Mahesh Virendra B

    2002-04-01

    Full Text Available Abstract Background Previous work by our group and others has implicated a role for kinins in the ovulatory process. The purpose of the present study was to elucidate whether endogenous progesterone, which is an intraovarian regulator of ovulation, might be responsible for induction of the kinin system in the ovary during ovulation. The gonadotropin-primed immature rat was used as the experimental model, and the role of endogenous progesterone was explored using the antiprogestin, RU486. Results The results of the study revealed that RU486 treatment, as expected, significantly attenuated ovulation. Activity of the kinin-generating enzyme, kallikrein, was elevated in the ovary in control animals prior to ovulation with peak values observed at 4 h post hCG, only to fall to low levels at 10 h, with a recovery at 20 h post hCG. RU486 treatment had no significant effect on ovarian kallikrein activity as compared to the control group. Total ovarian kininogen levels in control animals increased significantly at 12–14 h after hCG – coinciding with initiation of ovulation. Thereafter, ovarian kininogen levels fell to low levels at 20 h, only to show a rebound from 24–38 h post-hCG. RU486 treatment had no significant effect on the rise of total ovarian kininogen levels from 12–14 h after hCG; however, from 30–40 h post hCG, RU486-treated animals had significantly higher total ovarian kininogen levels versus control animals, suggesting that endogenous progesterone may act to restrain elevations of kininogens in the post-ovulatory ovary. This robust elevation of ovarian kininogen levels by RU486 was found to be primarily due to an increase in T-kininogen, which is a potent cysteine protease inhibitor. Conclusions Taken as a whole, these results suggest that endogenous progesterone does not regulate kallikrein activity or kininogens prior to ovulation, but may provide a restraining effect on T-kininogen levels in the post-ovulatory ovary.

  11. Altered glucose homeostasis and hepatic function in obese mice deficient for both kinin receptor genes.

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    Carlos C Barros

    Full Text Available The Kallikrein-Kinin System (KKS has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM, we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO. Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.

  12. Inhibition of vascular permeability by antisense-mediated inhibition of plasma kallikrein and coagulation factor 12.

    Science.gov (United States)

    Bhattacharjee, Gourab; Revenko, Alexey S; Crosby, Jeffrey R; May, Chris; Gao, Dacao; Zhao, Chenguang; Monia, Brett P; MacLeod, A Robert

    2013-06-01

    Hereditary angioedema (HAE) is a rare disorder characterized by recurrent, acute, and painful episodes of swelling involving multiple tissues. Deficiency or malfunction of the serine protease inhibitor C1 esterase inhibitor (C1-INH) results in HAE types 1 and 2, respectively, whereas mutations in coagulation factor 12 (f12) have been associated with HAE type 3. C1-INH is the primary inhibitor of multiple plasma cascade pathways known to be altered in HAE patients, including the complement, fibrinolytic, coagulation, and kinin-kallikrein pathways. We have selectively inhibited several components of both the kinin-kallikrein system and the coagulation cascades with potent and selective antisense oligonucleotides (ASOs) to investigate their relative contributions to vascular permeability. We have also developed ASO inhibitors of C1-INH and characterized their effects on vascular permeability in mice as an inducible model of HAE. Our studies demonstrate that ASO-mediated reduction in C1-INH plasma levels results in increased vascular permeability and that inhibition of proteases of the kinin-kallikrein system, either f12 or prekallikrein (PKK) reverse the effects of C1-INH depletion with similar effects on both basal and angiotensin converting enzyme (ACE) inhibitor-induced permeability. In contrast, inhibition of coagulation factors 11 (f11) or 7 (f7) had no effect. These results suggest that the vascular defects observed in C1-INH deficiency are dependent on the kinin-kallikrein system proteases f12 and PKK, and not mediated through the coagulation pathways. In addition, our results highlight a novel therapeutic modality that can potentially be employed prophylactically to prevent attacks in HAE patients.

  13. Kallikrein 1 is overexpressed by astrocytes in the hippocampus of patients with refractory temporal lobe epilepsy, associated with hippocampal sclerosis.

    Science.gov (United States)

    Simões, Priscila Santos Rodrigues; Perosa, Sandra Regina; Arganãraz, Gustavo Adolfo; Yacubian, Elza Márcia; Carrete, Henrique; Centeno, Ricardo Silva; Varella, Pedro Paulo Vasconcellos; Santiago, Joselita Ferreira Carvalho; Canzian, Mauro; Silva, Jose Antonio; Mortara, Renato Arruda; Amado, Débora; Cavalheiro, Esper Abrão; Mazzacoratti, Maria da Graça Naffah

    2011-03-01

    Kallikrein 1 (hK1) is a tissue enzyme responsible for kinin release in inflammatory cascade. This study was delineated to study the distribution and the co-localization of hK1 and kinin B1 and B2 receptors with glial and/or neuronal proteins markers, in the hippocampus of patients with refractory temporal lobe epilepsy, associated with hippocampal sclerosis (TLE-HS), comparing with control tissues. Hippocampal levels of KLK1 mRNA were also measured. hK1, kinin B1 and B2 receptors, NeuN and GFAP were analyzed using immunohistochemistry and confocal microscopy and KLK1 mRNA was quantified with real time PCR. Increased expression of hK1 by astrocytes co-localized with GFAP was found, contrasting with kinin B1 and B2 receptors, which were co-localized with NeuN in the sclerotic hippocampus. In addition, KLK1 mRNA was also up-regulated in same tissues. These data suggest an overexpression of kallikrein-kinin system and a neuron-glia interaction in the inflammatory process present in refractory TLE-HS.

  14. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

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    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  15. Kinin B1 and B2 receptors are overexpressed in the hippocampus of humans with temporal lobe epilepsy.

    Science.gov (United States)

    Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Goto, Eduardo Massatoshi; Costa, Luciana Gilbert Pessoa; Konno, Ana Carla; Varella, Pedro Paulo Vasconcellos; Santiago, Joselita Ferreira Carvalho; Pesquero, João Bosco; Canzian, Mauro; Amado, Debora; Yacubian, Elza Marcia; Carrete, Henrique; Centeno, Ricardo Silva; Cavalheiro, Esper Abrão; Silva, Jose Antonio; Mazzacoratti, Maria da Graça Naffah

    2007-01-01

    Molecular biology tools have been employed to investigate the participation of peptides in human temporal lobe epilepsy (TLE). Active polypeptides and their receptors have been related to several brain processes, such as inflammation, apoptosis, brain development, K(+) and Ca(2+) channels' activation, cellular growth, and induction of neuronal differentiation. Previous works have shown a neuroprotector effect for kinin B2 receptor and a deleterious, pro-epileptogenic action for kinin B1 receptor in animal models of TLE. The present work was delineated to analyze the kinin B1 and B2 receptors expression in the hippocampus of patients presenting refractory mesial TLE. The hippocampi were removed during the patients surgery in a procedure used for seizure control and compared with tissues obtained after autopsy. Nissl staining was performed to study the tissue morphology and immunohistochemistry, and Western blot was used to compare the distribution and levels of both receptors in the hippocampus. In addition, real time PCR was employed to analyze the gene expression of these receptors. Nissl staining showed sclerotic hippocampi with hilar, granular, and pyramidal cell loss in TLE patients. Immunohistochemistry and Western blot analyses showed increased expression of kinin B1 and B2 receptors but the real-time PCR data demonstrated increased mRNA level only for kinin B2 receptors, when compared with controls. These data show for the first time a relationship between human TLE and the kallikrein-kinin system, confirming ours previous results, obtained from experimental models of epilepsy.

  16. Kinin Receptor Antagonists as Potential Neuroprotective Agents in Central Nervous System Injury

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    Anna V Leonard

    2010-09-01

    Full Text Available Injury to the central nervous system initiates complex physiological, cellular and molecular processes that can result in neuronal cell death. Of interest to this review is the activation of the kinin family of neuropeptides, in particular bradykinin and substance P. These neuropeptides are known to have a potent pro-inflammatory role and can initiate neurogenic inflammation resulting in vasodilation, plasma extravasation and the subsequent development of edema. As inflammation and edema play an integral role in the progressive secondary injury that causes neurological deficits, this review critically examines kinin receptor antagonists as a potential neuroprotective intervention for acute brain injury, and more specifically, traumatic brain and spinal cord injury and stroke.

  17. Thrombin, kallikrein and complement C5b-9 adsorption on hydrophilic and hydrophobic titanium and glass after short time exposure to whole blood.

    Science.gov (United States)

    Yahyapour, Noushin; Eriksson, Cecilia; Malmberg, Per; Nygren, Håkan

    2004-07-01

    Hydrophilic and hydrophobic titanium and glass were exposed to capillary whole blood between 5s and 24h. The time-sequence for adsorption of thrombin, kallikrein and complement C5b-9, and their relationship with adherent platelets and polymorphonuclear granulocyte (PMN) activation were investigated. Adsorbed thrombin and kallikrein were measured by cleavage of specific chromogenic substances, S-2238 and S-2303, respectively. Complement C5b-9 and expression of CD11b, CD66b, CD62P and Pan-platelets were measured by immunofluorescence. Thrombin and kallikrein were present on the surfaces during the whole investigated periods. Platelet adhesion and PMN cell adhesion and activation on all surfaces and activation of platelets on hydrophobic surfaces showed a similar pattern to thrombin adsorption. Kallikrein adsorption had a different pattern on each surface. C5b-9 was detected between 32min and 24h of blood exposure and a varying pattern of C5b-9 coverage was observed on each surface. In conclusion, our results indicate that the interaction between material and blood coagulation and kinin-activating proteins regulate the adhesion and activation of blood cells, whereas after longer time the coagulation and kallikrein-kinin system play minor roles and the complement system is decisive for mediating and elongating the inflammatory process.

  18. Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation.

    Science.gov (United States)

    Ekdahl, Kristina N; Teramura, Yuji; Hamad, Osama A; Asif, Sana; Duehrkop, Claudia; Fromell, Karin; Gustafson, Elisabet; Hong, Jaan; Kozarcanin, Huda; Magnusson, Peetra U; Huber-Lang, Markus; Garred, Peter; Nilsson, Bo

    2016-11-01

    Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.

  19. Kallikrein from rat submandibular gland, cloning and sequencing of rKLK1

    Energy Technology Data Exchange (ETDEWEB)

    Xavier, L.P.; Fernandes, H.C.; Figueiredo, A.F.S.; Pesquero, J.L.; Santoro, M.M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Bioquimica e Imunologia

    2008-07-01

    Full text: Tissue kallikreins are closely related serine proteases that are present in all mammals and expressed in a wide variety of cells and tissues. Little is known about the physiological role of tissue kallikreins, except that the kallikreins 1 (K1) can release kinins from low- and/or high-Mr kininogen in all species. In this work, the rat tissue kallikrein from submandibular gland was purified, characterized by SDS-PAGE and mass spectrometry, and the protein was identified as rat true tissue kallikrein (rK1). Molecular techniques that permit to obtain recombinant proteins expressed in milligram quantities were used in order to allow the realization of the studies of structure-function, substrate specificity and susceptibility to inhibitors using kinetic, calorimetric and crystallographic assays. Therefore, the total RNA from submandibular gland was isolated using the Tri zol reagent and its purity was evaluated by electrophoresis on agarose gel. Reverse transcription was performed according to the manufacturer's protocol. The resulting cDNA was then used for PCR which was performed with cDNA and platinum TaqDNA polymerase; the reactions were carried out according to the manufacturer. The PCR mixture contained sense and antisense primers, with sites for the restriction enzymes XhoI and NotI, respectively, which were designed to tissue kallikrein gene, rKLK1. The amplified band of 750 bp was excised, purified from agarose gel, cloned in pGemT-easy vector, transformed in E. coli and colonies were selected. In order to purify the plasmids from the colonies it was used the Mini prep system. The analysis of plasmids sequence confirmed the insertion of the gene. In the moment rKLK1 will be cloned in the pPIC9 vector and integrated into the yeast genome.

  20. Interaction of Bacteroides fragilis and Bacteroides thetaiotaomicron with the kallikrein–kinin system

    Science.gov (United States)

    Mörgelin, Matthias; Cooney, Jakki C.; Frick, Inga-Maria

    2011-01-01

    Many bacterial pathogens interfere with the contact system (kallikrein–kinin system) in human plasma. Activation of this system has two consequences: cleavage of high-molecular-mass kininogen (HK) resulting in release of the potent proinflammatory peptide bradykinin, and initiation of the intrinsic pathway of coagulation. In this study, two species of the Gram-negative anaerobic commensal organism Bacteroides, namely Bacteroides fragilis and Bacteroides thetaiotaomicron, were found to bind HK and fibrinogen, the major clotting protein, from human plasma as shown by immunoelectron microscopy and Western blot analysis. In addition, these Bacteroides species were capable of activating the contact system at its surface leading to a significant prolongation of the intrinsic coagulation time and also to the release of bradykinin. Members of the genus Bacteroides have been known to act as opportunistic pathogens outside the gut, with B. fragilis being the most common isolate from clinical infections, such as intra-abdominal abscesses and bacteraemia. The present results thus provide more insight into how Bacteroides species cause infection. PMID:21527472

  1. Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

    Science.gov (United States)

    Zou, Xia; Zhang, Xiao-xi; Liu, Xin-yu; Li, Rong; Wang, Min; Wu, Wei-jie; Sui, Yi; Zhao, Hai-lu

    2015-01-01

    Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS) on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN). Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF-) β and α-smooth muscle action (SMA). Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P < 0.05). Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response. PMID:25918729

  2. Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Xia Zou

    2015-01-01

    Full Text Available Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN. Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF- β and α-smooth muscle action (SMA. Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05. Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

  3. Preclinical characterization of recombinant human tissue kallikrein-1 as a novel treatment for type 2 diabetes mellitus.

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    Tadeusz Kolodka

    Full Text Available Modulation of the kallikrein-kinin system (KKS has been shown to have beneficial effects on glucose homeostasis and several other physiological responses relevant to the progression of type 2 diabetes mellitus (T2D. The importance of bradykinin and its receptors in mediating these responses is well documented, but the role of tissue kallikrein-1, the protease that generates bradykinin in situ, is much less understood. We developed and tested DM199, recombinant human tissue kallikrein-1 protein (rhKLK-1, as a potential novel therapeutic for T2D. Hyperinsulinemic-euglycemic clamp studies suggest that DM199 increases whole body glucose disposal in non-diabetic rats. Single-dose administration of DM199 in obese db/db mice and ZDF rats, showed an acute, dose-dependent improvement in whole-body glucose utilization. Sub-acute dosing for a week in ZDF rats improved glucose utilization, with a concomitant rise in fasting insulin levels and HOMA1-%B scores. After cessation of sub-acute dosing, fasting blood glucose levels were significantly lower in ZDF rats during a drug wash-out period. Our studies show for the first time that DM199 administration results in acute anti-hyperglycemic effects in several preclinical models, and demonstrate the potential for further development of DM199 as a novel therapeutic for T2D.

  4. Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

    OpenAIRE

    Xia Zou; Xiao-xi Zhang; Xin-yu Liu; Rong Li; Min Wang; Wei-jie Wu; Yi Sui; Hai-lu Zhao

    2015-01-01

    Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS) on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN). Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histop...

  5. Protease Inhibitors Extracted from Caesalpinia echinata Lam. Affect Kinin Release during Lung Inflammation

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    Ilana Cruz-Silva

    2016-01-01

    Full Text Available Inflammation is an essential process in many pulmonary diseases in which kinins are generated by protease action on kininogen, a phenomenon that is blocked by protease inhibitors. We evaluated kinin release in an in vivo lung inflammation model in rats, in the presence or absence of CeKI (C. echinata kallikrein inhibitor, a plasma kallikrein, cathepsin G, and proteinase-3 inhibitor, and rCeEI (recombinant C. echinata elastase inhibitor, which inhibits these proteases and also neutrophil elastase. Wistar rats were intravenously treated with buffer (negative control or inhibitors and, subsequently, lipopolysaccharide was injected into their lungs. Blood, bronchoalveolar lavage fluid (BALF, and lung tissue were collected. In plasma, kinin release was higher in the LPS-treated animals in comparison to CeKI or rCeEI groups. rCeEI-treated animals presented less kinin than CeKI-treated group. Our data suggest that kinins play a pivotal role in lung inflammation and may be generated by different enzymes; however, neutrophil elastase seems to be the most important in the lung tissue context. These results open perspectives for a better understanding of biological process where neutrophil enzymes participate and indicate these plant inhibitors and their recombinant correlates for therapeutic trials involving pulmonary diseases.

  6. Contribution of the central dopaminergic system in the anti-hypertensive effect of kinin B1 receptor antagonists in two rat models of hypertension.

    Science.gov (United States)

    De Brito Gariepy, H; Carayon, P; Ferrari, B; Couture, R

    2010-04-01

    Kinins are neuroactive peptides that could play a role in central autonomic control of blood pressure. Whereas kinin B1R binding sites were increased in specific brain areas of spontaneously hypertensive rats (SHR) and Angiotensin II (AngII)-hypertensive rats, the contribution of kinin B1R in hypertension remains controversial. The aims of the study were to determine: (a) the effects on mean arterial blood pressure (MAP) of centrally and peripherally administered B1R antagonists in SHR (16weeks) and AngII-hypertensive rats (200ng/kg/minx2weeks, s.c.); (b) the contribution of central dopamine in the effects of SSR240612. The rationale is based on the overactivity of the dopaminergic system in hypertension. In both models, SSR240612 (1, 5 and 10mg/kg, gavage) reduced dose-dependently MAP (-75mm Hg at least up to 6-8h) and this therapeutic effect was resolved after 24h. At the dose of 5mg/kg, SSR240612-induced anti-hypertension was prevented by two dopamine receptor blockers, namely raclopride (0.16mg/kg, i.v.) and haloperidol (10mg/kg, s.c.). I.c.v. SSR240612 (1mug) decreased rapidly MAP in both models (1-6h) via a raclopride sensitive mechanism. In comparison, peripherally acting B1R antagonists (R-715 and R-954, 2mg/kg, s.c.) caused shorter and very modest decreases of MAP (from -20 to -30mm Hg). Centrally or peripherally administered B1R antagonists had no effect on MAP in control Wistar-Kyoto rats. Data provide the first pharmacological evidence that the up-regulated brain kinin B1R contributes through a central dopaminergic mechanism (DA-D2R) to the maintenance of arterial hypertension in genetic and experimental animal models of hypertension.

  7. Mast Cell Coupling to the Kallikrein–Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease

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    Clarissa R. Nascimento

    2017-08-01

    Full Text Available During the course of Chagas disease, infectious forms of Trypanosoma cruzi are occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate sentinel cells via toll-like receptor 2 (TLR2. Upon plasma extravasation, proteolytically derived kinins and C5a stimulate immunoprotective Th1 responses via cross-talk between bradykinin B2 receptors (B2Rs and C5aR. Awareness that TCTs invade cardiovascular cells in vitro via interdependent activation of B2R and endothelin receptors [endothelin A receptor (ETAR/endothelin B receptor (ETBR] led us to hypothesize that T. cruzi might reciprocally benefit from the formation of infection-associated edema via activation of kallikrein–kinin system (KKS. Using intravital microscopy, here we first examined the functional interplay between mast cells (MCs and the KKS by topically exposing the hamster cheek pouch (HCP tissues to dextran sulfate (DXS, a potent “contact” activator of the KKS. Surprisingly, although DXS was inert for at least 30 min, a subtle MC-driven leakage resulted in factor XII (FXII-dependent activation of the KKS, which then amplified inflammation via generation of bradykinin (BK. Guided by this mechanistic insight, we next exposed TCTs to “leaky” HCP—forged by low dose histamine application—and found that the proinflammatory phenotype of TCTs was boosted by BK generated via the MC/KKS pathway. Measurements of footpad edema in MC-deficient mice linked TCT-evoked inflammation to MC degranulation (upstream and FXII-mediated generation of BK (downstream. We then inoculated TCTs intracardiacally in mice and found a striking decrease of parasite DNA (quantitative polymerase chain reaction; 3 d.p.i. in the heart of MC-deficient mutant mice. Moreover, the intracardiac parasite load was significantly reduced in WT

  8. [Analysis of the role of neurohumoral systems in action of dopaminomimetic dopamine on ion-regulating renal function].

    Science.gov (United States)

    Landar', L N; Kuz'min, O B

    2013-01-01

    Dopamine causes in anesthetized rats expressed diuretic response that is accompanied by an increase in GRF and a significant enhance of sodium and potassium excretion. Pretreatment the animals in diclofenac sodium or contrical in doses, that inhibit respectively activity of renal PG-system and kallikrein-kinin system, don't prevent of renal effects of dopamine. Preliminary assignment a direct renin inhibitor aliskiren enhances the diuretic, natriuretic and kaliyuretic effects of the drug. It is concluded that renal PG-system and kallikrein-kinin system are not involved in the formation of renal effects of dopamine. Renal tissue RAS directly included in the mechanism of action of dopamine in the kidney, acting as a modulator, preventing excessive loss of water and electrolytes with urine.

  9. Genome-wide association reveals that common genetic variation in the kallikrein-kinin system is associated with serum L-arginine levels.

    Science.gov (United States)

    Zhang, Weihua; Jernerén, Fredrik; Lehne, Benjamin C; Chen, Ming-Huei; Luben, Robert N; Johnston, Carole; Elshorbagy, Amany; Eppinga, Ruben N; Scott, William R; Adeyeye, Elizabeth; Scott, James; Böger, Rainer H; Khaw, Kay-Tee; van der Harst, Pim; Wareham, Nicholas J; Vasan, Ramachandran S; Chambers, John C; Refsum, Helga; Kooner, Jaspal S

    2016-11-30

    L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic factors determining serum L-arginine levels, amongst 901 Europeans and 1,394 Indian Asians. We show that common genetic variations at the KLKB1 and F12 loci are strongly associated with serum L-arginine levels. The G allele of single nucleotide polymorphism (SNP) rs71640036 (T/G) in KLKB1 is associated with lower serum L-arginine concentrations (10 µmol/l per allele copy, p=1×10(-24)), while allele T of rs2545801 (T/C) near the F12 gene is associated with lower serum L-arginine levels (7 µmol/l per allele copy, p=7×10(-12)). Together these two loci explain 7 % of the total variance in serum L-arginine concentrations. The associations at both loci were replicated in independent cohorts with plasma L-arginine measurements (pL-arginine and its potential relationship with cardiovascular risk.

  10. Genome-wide association reveals that common genetic variation in the kallikrein-kinin system is associated with serum L-arginine levels

    NARCIS (Netherlands)

    Zhang, Weihua; Jerneren, Fredrik; Lehne, Benjamin C.; Chen, Ming-Huei; Luben, Robert N.; Johnston, Carole; Elshorbagy, Amany; Eppinga, Ruben N.; Scott, William R.; Adeyeye, Elizabeth; Scott, James; Boeger, Rainer H.; Khaw, Kay-Tee; van der Harst, Pim; Wareham, Nicholas J.; Vasan, Ramachandran S.; Chambers, John C.; Refsum, Helga; Kooner, Jaspal S.

    2016-01-01

    L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic

  11. Kinin B1 receptors mediate depression-like behavior response in stressed mice treated with systemic E. coli lipopolysaccharide

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    Campos Maria M

    2010-12-01

    Full Text Available Abstract Background Kinin B1 receptors are inducible molecules up-regulated after inflammatory stimuli. This study evaluated the relevance of kinin B1 receptors in a mouse depression behavior model. Methods Mice were exposed to a 5-min swimming session, and 30 min later they were injected with E. coli lipopolysaccharide (LPS. Depression-like behavior was assessed by determining immobility time in a tail suspension test. Different brain structures were collected for molecular and immunohistochemical studies. Anhedonia was assessed by means of a sucrose intake test. Results Our protocol elicited an increase in depression-like behavior in CF1 mice, as assessed by the tail-suspension test, at 24 h. This behavior was significantly reduced by treatment with the selective B1 receptor antagonists R-715 and SSR240612. Administration of SSR240612 also prevented an increase in number of activated microglial cells in mouse hippocampus, but did not affect a reduction in expression of mRNA for brain-derived neurotrophic factor. The increased immobility time following LPS treatment was preceded by an enhancement of hippocampal and cortical B1 receptor mRNA expression (which were maximal at 1 h, and a marked production of TNFα in serum, brain and cerebrospinal fluid (between 1 and 6 h. The depression-like behavior was virtually abolished in TNFα p55 receptor-knockout mice, and increased B1 receptor mRNA expression was completely absent in this mouse strain. Furthermore, treatment with SSR240612 was also effective in preventing anhedonia in LPS-treated mice, as assessed using a sucrose preference test. Conclusion Our data show, for the first time, involvement of kinin B1 receptors in depressive behavioral responses, in a process likely associated with microglial activation and TNFα production. Thus, selective and orally active B1 receptor antagonists might well represent promising pharmacological tools for depression therapy.

  12. Evidence for the promoting role of the intra-uterine kinin release in the development of late hypertonic saline-induced abortion.

    Science.gov (United States)

    Makevnina, L G; Nikonov, A P; Goncharova, V N; Morozova, M S; Paskhina, T S

    1996-06-01

    Blood plasma kininogen (K), kininases (KS), kallikrein (KK), prekallikrein (PKK), and PGF2a were estimated in the common circulation of pregnant women during late saline-induced abortion and also in retroplacental blood after foetus delivery. The results provide evidence for intra-uterine kinin release from circulating blood K by locally activated KK from the very beginning of abortion. The greatest kinin release coincided with the strongest KS activity decrease at the time of foetus delivery. The pre-abortive KS levels correlated directly with abortus duration. Uterine PG biosynthesis was activated, but appeared to be a secondary process.

  13. Kinins as mediators of intestinal secretion.

    Science.gov (United States)

    Gaginella, T S; Kachur, J F

    1989-01-01

    Kinins are small peptides that have diverse biological actions. Concentrations of kinins in the nanomolar or subnanomolar range induce intestinal smooth muscle contraction and evoke mucosal electrolyte secretion. Hyperkininemia is associated with effects on gastrointestinal motility and intestinal mucosal inflammation. Bradykinin and kallidin are the predominant kinins with effects on the gastrointestinal tract of mammals. Bradykinin stimulates chloride ion secretion by the guinea pig and rabbit ileum, rabbit colon, rat colon and monolayers of human HCA-7 cells. Kinins directly or indirectly stimulate phospholipase A2 and phospholipase C. Cells in the lamina propria of the mucosa (e.g., fibroblasts, mast cells, leukocytes), by liberating cyclooxygenase and lipoxygenase metabolites of arachidonic acid, are involved in the kinin response; direct effects on epithelial cells cannot be ruled out, however. Antagonists now exist for kinin receptors. Based on studies with these antagonists in smooth muscle preparations, two subgroups of kinin receptor have been identified. The B2-type receptor appears to be responsible for both the contraction of ileal muscle and ileal secretion. Kinins are probably more important as pathophysiological rather than as physiological mediators. They may amplify the effect of inflammatory products that induce intestinal secretion. The precise involvement of kinins in clinical mucosal secretory states and diarrhea will require quantitative assessment of their levels during each phase of mucosal inflammation. Additional studies on the mechanism of action of kinins will be essential in designing therapy to mitigate the symptoms associated with mucosal inflammation.

  14. Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy

    Science.gov (United States)

    Cao, Buqing; Yu, Qing; Zhao, Wei; Tang, Zhiping; Cong, Binghai; Du, Jiankui; Lu, Jianqiang; Zhu, Xiaoyan; Ni, Xin

    2016-01-01

    The tissue kallikrein-related peptidase family (KLK) is a group of trypsin- and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown. In the present study, we demonstrated for the first time that KLK8 was expressed in myocardium. KLK8 expression was upregulated in left ventricle of cardiac hypertrophy models. Both intra-cardiac adenovirus-mediated and transgenic-mediated KLK8 overexpression led to cardiac hypertrophy in vivo. In primary neonatal rat cardiomyocytes, KLK8 knockdown inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas KLK8 overexpression promoted cardiomyocyte hypertrophy via a serine protease activity-dependent but kinin receptor-independent pathway. KLK8 overexpression increased epidermal growth factor (EGF) production, which was blocked by the inhibitors of serine protease. EGF receptor (EGFR) antagonist and EGFR knockdown reversed the hypertrophy induced by KLK8 overexpression. KLK8-induced cardiomyocyte hypertrophy was also significantly decreased by blocking the protease-activated receptor 1 (PAR1) or PAR2 pathway. Our data suggest that KLK8 may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway. It is implied that different KLK family members can subtly regulate cardiac function and remodeling. PMID:26823023

  15. Kinin receptors in skin wound healing.

    Science.gov (United States)

    Soley, Bruna da Silva; Morais, Rafael Leite Tavares de; Pesquero, João Bosco; Bader, Michael; Otuki, Michel Fleith; Cabrini, Daniela Almeida

    2016-05-01

    Wound healing is a complex and dynamic process that includes 3 different phases: inflammation, proliferation, and remodeling. Kinins are vasoactive peptides released after tissue injury, and are directly involved in the development and maintenance of inflammatory processes, and their actions are mediated by the activation of receptors called B1 and B2. We aimed to evaluate the involvement of kinin receptors in the skin healing process. Knockout mice for kinin receptors (KOB1, KOB2 and KOB1B2) and wild type controls (WT) were subjected to a skin excision model, and tissue repair process was evaluated during different phases of wound healing. In knockout animals for kinin receptors differences were observed in the resolution period of injury exceeding 17 days for the total closure of wounds. The absence of kinin receptors promotes a significant reduction in infiltration of polymorphonuclear cells on day 2 of the inflammatory phase. Already at the late stage of this phase (3 days) there was a negative influence on the infiltration of polymorphonuclear and mononuclear cells at the site of injury in comparison to WT. Collagen was significantly diminished in tissue of KOB1, KOB2 and KOB1B2 from day two to the end of the healing process. Moreover, wound tissue from KOB2 and KOB1B2, but not KOB1, presented impaired parameters of re-epitheliazation, reduced proliferation of cells (PCNA immunostaining), and a lower number of myofibroblasts (α-SMA immunostaining). These data reveal the involvement of kinin receptors in processes of skin repair. Both kinin receptors participate especially during the inflammatory phase, while B2 receptors seem to be more relevant in the quality of the wound scar. Thus, a better understanding of the contribution of kinins to skin wound healing may reveal novel options for therapy. Copyright © 2016. Published by Elsevier Ireland Ltd.

  16. Comparative genomic analysis of eutherian kallikrein genes

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    Marko Premzl

    2017-03-01

    Full Text Available The present study made attempts to update and revise eutherian kallikrein genes implicated in major physiological and pathological processes and in medical molecular diagnostics. Using eutherian comparative genomic analysis protocol and free available genomic sequence assemblies, the tests of reliability of eutherian public genomic sequences annotated most comprehensive curated third party data gene data set of eutherian kallikrein genes including 121 complete coding sequences among 335 potential coding sequences. The present analysis first described 13 major gene clusters of eutherian kallikrein genes, and explained their differential gene expansion patterns. One updated classification and nomenclature of eutherian kallikrein genes was proposed, as new framework of future experiments.

  17. Modulation of C1-Inhibitor and Plasma Kallikrein Activities by Type IV Collagen

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    Sriram Ravindran

    2012-01-01

    Full Text Available The contact system of coagulation can be activated when in contact with biomaterials. As collagen is being tested in novel biomaterials in this study, we have investigated how type IV collagen affects plasma kallikrein and C1-inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of 0.86 μM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and β-factor XIIa activity and on C1-inhibitor function were determined. Factor XIIa rapidly lost activity in the presence of type IV collagen, whereas plasma kallikrein and β-factor XIIa were more stable. The rate of inhibition of plasma kallikrein by C1-inhibitor was decreased by type IV collagen in a dose-dependent manner. These studies could be relevant to the properties of biomaterials, which contain collagen, and should be considered in the testing for biocompatibility.

  18. Coordination ability of insect kinin analogs

    Science.gov (United States)

    Spectroscopic data, including electronic absorption, CD and EPR results, as well as theoretical calculations have shown that the insertion of 4-aminopyroglutamate, a novel cis-ppetide bond mimic, in the insect kinin peptide leads to an effective ligand towards Cu(II) ions at basic pH ranges. The 4-a...

  19. Kinetic and thermodynamic characterization of the interactions between the components of human plasma kinin-forming system and isolated and purified cell wall proteins of Candida albicans.

    Science.gov (United States)

    Seweryn, Karolina; Karkowska-Kuleta, Justyna; Wolak, Natalia; Bochenska, Oliwia; Kedracka-Krok, Sylwia; Kozik, Andrzej; Rapala-Kozik, Maria

    2015-01-01

    Cell wall proteins of Candida albicans, besides their best known role in the adhesion of this fungal pathogen to host's tissues, also bind some soluble proteins, present in body fluids and involved in maintaining the biochemical homeostasis of the human organism. In particular, three plasma factors - high-molecular-mass kininogen (HK), factor XII (FXII) and prekallikrein (PPK) - have been shown to adhere to candidal cells. These proteins are involved in the surface-contact-catalyzed production of bradykinin-related peptides (kinins) that contribute to inflammatory states associated with microbial infections. We recently identified several proteins, associated with the candidal cell walls, and probably involved in the binding of HK. In our present study, a list of potential FXII- and PPK-binding proteins was proposed, using an affinity selection (on agarose-coupled FXII or PPK) from a whole mixture of β-1,3-glucanase-extrated cell wall-associated proteins and the mass-spectrometry protein identification. Five of these fungal proteins, including agglutinin-like sequence protein 3 (Als3), triosephosphate isomerase 1 (Tpi1), enolase 1 (Eno1), phosphoglycerate mutase 1 (Gpm1) and glucose-6-phosphate isomerase 1 (Gpi1), were purified and characterized in terms of affinities to the human contact factors, using the surface plasmon resonance measurements. Except Gpm1 that bound only PPK, and Als3 that exhibited an affinity to HK and FXII, the other isolated proteins interacted with all three contact factors. The determined dissociation constants for the identified protein complexes were of 10(-7) M order, and the association rate constants were in a range of 10(4)-10(5) M(-1)s(-1). The identified fungal pathogen-host protein interactions are potential targets for novel anticandidal therapeutic approaches.

  20. Effect of glandular kallikrein on distal bicarbonate transport. Role of basolateral Cl-/HCO3- exchanger and vacuolar H(+)-ATPase.

    Science.gov (United States)

    Manucha, W; Vallés, P

    1999-12-01

    The luminal membrane of collecting duct cells, specially the intercalated cells, is normally exposed to active kallikrein. This is due to the specific localization of renal kallikrein in the connecting tubule cells. We have previously reported inhibition of distal bicarbonate secretion by renal kallikrein. The present study was performed to evaluate the participation of basolateral Cl-/HCO3- exchanger and luminal H(+)-ATPase activity of cortical collecting duct segments (CCD) in the mechanism involved in the inhibition of bicarbonate secretion induced by the enzyme. The effect of orthograde injections of 1 microgram/ml (250 U/6.3 mg) pig pancreatic kallikrein, in the absence and presence of 1 mM DIDS (stilbene-disulfonic acid) in the renal tubule system, was evaluated. Urine fractions were collected after two-minutes stop-flow. Changes in the urine fraction (Fr) related to those in free-flow urine samples (Ff) were related to the respective polyfructosan (Inutest) ratio. Renal kallikrein activity (Fr:Ff kallikrein/Fr:Ff polyfructosan) increased significantly in the first 120 microliters urine fraction collected after glandular 1 microgram/ml kallikrein, P Bicarbonate secretion rate (Fr:Ff HCO3-/Fr:Ff polyfructosan) of collecting ducts was significantly reduced in the first 120 microliters urine fraction collected, related to control, during the first and second stop-flow periods. No difference was shown in bicarbonate excretion between the first 120 microliters urine fractions collected after administration of glandular kallikrein and glandular kallikrein plus DIDS. To measure H(+)-ATPase activity, rat microdissected cortical collector tubules (CCD) were incubated in the presence of increasing glandular kallikrein doses (A: 93, B: 187 and C: 375 mU/200 microL) in the presence of ouabain (4 microM) and omeprazole (100 microM) to inhibit Na(+)-K(+)-ATPase and H(+)-K(+)-ATPase, respectively. In CCD, bafilomycin-sensitive H(+)-ATPase activity (pmol/mm/min) after

  1. Leucaena leucocephala serine proteinase inhibitor: primary structure and action on blood coagulation, kinin release and rat paw edema.

    Science.gov (United States)

    Oliva, M L; Souza-Pinto, J C; Batista, I F; Araujo, M S; Silveira, V F; Auerswald, E A; Mentele, R; Eckerskorn, C; Sampaio, M U; Sampaio, C A

    2000-03-07

    A serine proteinase inhibitor isolated from Leucaena leucocephala seeds (LlTI) was purified to homogeneity by acetone fractionation, ion exchange chromatography, gel filtration and reverse phase chromatography (HPLC). SDS-PAGE indicated a protein with M(r) 20000 and two polypeptide chains (alpha-chain, M(r) 15000, and beta-chain, M(r) 5000), the sequence being determined by automatic Edman degradation and by mass spectroscopy. LlTI is a 174 amino acid residue protein which shows high homology to plant Kunitz inhibitors, especially those double chain proteins purified from the Mimosoideae subfamily. LlTI inhibits plasmin (K(i) 3.2 x 10(-10) M), human plasma kallikrein (K(i) 6.3 x 10(-9) M), trypsin (K(i) 2.5 x 10(-8) M) and chymotrypsin (K(i) 1.4 x 10(-8) M). Factor XIIa activity is inhibited but K(i) was not determined, and factor Xa, tissue kallikrein and thrombin are not inhibited by LlTI. The action of LlTI on enzymes that participate in the blood clotting extrinsic pathway is confirmed by the prolongation of activated partial thromboplastin time, used as clotting time assay. The inhibition of the fibrinolytic activity of plasmin was confirmed on the hydrolysis of fibrin plates. LlTI inhibits kinin release from high molecular weight kininogen by human plasma kallikrein in vitro and, administered intravenously, causes a decrease in paw edema induced by carrageenin or heat in male Wistar rats. In addition, lower concentrations of bradykinin were found in limb perfusion fluids of LlTI-treated rats.

  2. Modulation of C1-Inhibitor and Plasma Kallikrein Activities by Type IV Collagen

    OpenAIRE

    Sriram Ravindran; Marc Schapira; Patston, Philip A.

    2012-01-01

    The contact system of coagulation can be activated when in contact with biomaterials. As collagen is being tested in novel biomaterials in this study, we have investigated how type IV collagen affects plasma kallikrein and C1-inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of 0.86 μM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and β-factor XIIa activity and on C1-inhibitor function were determined. Factor XIIa rapidly lost activity in the...

  3. A novel signaling pathway of tissue kallikrein in promoting keratinocyte migration: Activation of proteinase-activated receptor 1 and epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Lin; Chao, Lee [Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425-2211 (United States); Chao, Julie, E-mail: chaoj@musc.edu [Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425-2211 (United States)

    2010-02-01

    Biological functions of tissue kallikrein (TK, KLK1) are mainly mediated by kinin generation and subsequent kinin B2 receptor activation. In this study, we investigated the potential role of TK and its signaling pathways in cultured human keratinocyte migration and in a rat skin wound healing model. Herein, we show that TK promoted cell migration and proliferation in a concentration- and time-dependent manner. Inactive TK or kinin had no significant effect on cell migration. Interestingly, cell migration induced by active TK was not blocked by icatibant or L-NAME, indicating an event independent of kinin B2 receptor and nitric oxide formation. TK's stimulatory effect on cell migration was inhibited by small interfering RNA for proteinase-activated receptor 1 (PAR{sub 1}), and by PAR{sub 1} inhibitor. TK-induced migration was associated with increased phosphorylation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK), which was blocked by inhibition of protein kinase C (PKC), Src, EGFR and ERK. TK-induced cell migration and EGFR phosphorylation were blocked by metalloproteinase (MMP) inhibitor, heparin, and antibodies against EGFR external domain, heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR). Local application of TK promoted skin wound healing in rats, whereas icatibant and EGFR inhibitor blocked TK's effect. Skin wound healing was further delayed by aprotinin and neutralizing TK antibody. This study demonstrates a novel role of TK in skin wound healing and uncovers new signaling pathways mediated by TK in promoting keratinocyte migration through activation of the PAR{sub 1}-PKC-Src-MMP pathway and HB-EGF/AR shedding-dependent EGFR transactivation.

  4. FACTOR-XII FRAGMENT AND KALLIKREIN GENERATION IN PLASMA DURING INCUBATION WITH BIOMATERIALS

    NARCIS (Netherlands)

    VANDERKAMP, KWHJ; VANOEVEREN, W

    Blood biocompatibility of medical devices is in many ways dependent on surface characteristics and biochemical blood material interactions. In this study, the contact system, in which the activation of factor XII and plasma kallikrein is included, is highlighted. This article describes a simple

  5. The renin-angiotensin system and its blockers

    Directory of Open Access Journals (Sweden)

    Igić Rajko

    2014-01-01

    Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

  6. Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

    Science.gov (United States)

    Liu, Kui; Li, Quan-Zhen; Delgado-Vega, Angelica M.; Abelson, Anna-Karin; Sánchez, Elena; Kelly, Jennifer A.; Li, Li; Liu, Yang; Zhou, Jinchun; Yan, Mei; Ye, Qiu; Liu, Shenxi; Xie, Chun; Zhou, Xin J.; Chung, Sharon A.; Pons-Estel, Bernardo; Witte, Torsten; de Ramón, Enrique; Bae, Sang-Cheol; Barizzone, Nadia; Sebastiani, Gian Domenico; Merrill, Joan T.; Gregersen, Peter K.; Gilkeson, Gary G.; Kimberly, Robert P.; Vyse, Timothy J.; Kim, Il; D’Alfonso, Sandra; Martin, Javier; Harley, John B.; Criswell, Lindsey A.; Wakeland, Edward K.; Alarcón-Riquelme, Marta E.; Mohan, Chandra

    2009-01-01

    Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody–induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody–induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody–induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody–induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody–induced nephritis and lupus. PMID:19307730

  7. Characterization of kinin receptors by bioassays.

    Science.gov (United States)

    Gobeil, F; Regoli, D

    1994-08-01

    1. Using the classical pharmacological criteria recommended by Schild, namely the order of potency of selective agonists (e.g., bradykinin, desArg9-bradykinin, [Hyp3]BK and [Aib7]BK) and the apparent affinity of competitive antagonists (e.g., DArg[Hyp3,DPhe7,Leu8]BK and WIN 64338), we have attempted to characterize B2 receptor subtypes. It has been shown that vascular tissues (e.g., dog carotid and renal arteries, rabbit jugular vein and rabbit aorta) are very sensitive to kinin agonists and antagonists (pD2 and pA2 values for BK and HOE 140 on B2 receptors are 8.5-10.1 and 9.2-9.4, respectively, and for desArg9BK and desArg9[Leu8]BK on B1 receptors they are 7.3-8.6 and 7.3-7.8, respectively). Mechanisms of action of kinins differ between pharmacological preparations. Kinin may act directly on the smooth muscle (e.g., rabbit jugular vein and rabbit aorta) as well as indirectly through other endogenous mediators such as nitric oxide (EDRF) (e.g., dog carotid and renal arteries) and prostaglandins (e.g., dog renal artery). 2. Pharmacological analysis of rabbit jugular vein (RJV) and guinea pig ileum (GPI) has revealed different sensitivities to certain synthetic analogs of BK and to competitive B2 receptor antagonists between the two tissues. 3. Agonist order of potency ([Hyp3]BK > BK > [Aib7]BK) obtained for RJV differed from that obtained for GPI (BK > or = [Aib7]BK > [Hyp3]BK). Competitive antagonists such as DArg[Hyp3, DPhe7, Leu8]BK and WIN 64338 discriminate in favor of B2A (RJV) and B2B (GPI) receptor subtypes, respectively. These data demonstrate the existence of B2 receptor subtypes. Correlation between data obtained in the present study and those reported for binding to the human B2 receptor support the view that the human receptor is similar to that of the rabbit.

  8. Gene structure and chromosomal localization of plasma kallikrein

    Energy Technology Data Exchange (ETDEWEB)

    Beaubien, G.; Mbikay, M.; Chretien, M.; Seidah, N.G. (Clinical Research Institute of Montreal, Quebec (Canada)); Rosinski-Chupin, I. (Inst. Pasteur, Paris (France)); Mattei, M.G. (Groupe hospitalier de a Timone, Marseille (France))

    1991-02-12

    Plasma kallikrein (Fletcher factor) is a hepatic serine proteinase that participates in the early phase of blood coagulation. From two genomic libraries, the authors succeeded to isolate four overlapping clones representing the entire rat plasma kallikrein gene. Using selective DNA sequencing, polymerase chain reactions, and restriction mapping, the authors demonstrated that the gene for rat plasma kallikrein was 22 kb in length. Similar to human factor XI the authors also found that the plasma kallikrein gene is composed of 15 exons and 14 introns. A potential transcription initiation step was determined by a novel application of the polymerase chain reaction technique. Computer analysis of the 5{prime}-promoter region of this gene revealed some putative control elements that might regulate the rat plasma kallikrein gene expression. These data and the results of chromosomal localization reported in the present study for mouse (chromosome 8) and human (chromosome 4) plasma kallikrein genes strongly corroborate a genic duplication event from a common ancestor to both plasma kallikrein and factor XI.

  9. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

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    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  10. Crystallization and preliminary crystallographic studies of human kallikrein 7, a serine protease of the multigene kallikrein family

    Energy Technology Data Exchange (ETDEWEB)

    Fernández, Israel S. [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Ständker, Ludger [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Hannover Medical School, Center of Pharmacology, 30625 Hannover (Germany); Forssmann, Wolf-Georg [Hannover Medical School, Center of Pharmacology, 30625 Hannover (Germany); Giménez-Gallego, Guillermo; Romero, Antonio, E-mail: romero@cib.csic.es [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain)

    2007-08-01

    The cloning, expression, purification and crystallization of recombinant human kallikrein 7, directly synthesized in the active form in E. coli, is described. Diffraction data were collected to 2.8 Å resolution from native crystals. Human kallikreins are a group of serine proteases of high sequence homology whose genes are grouped as a single cluster at chromosome 19. Although the physiological roles of kallikreins are generally still unknown, members of the kallikrein family have been clearly implicated in pathological situations such as cancer and psoriasis. Human kallikrein 7 (hK7) has been shown to be involved in pathological keratinization, psoriasis and ovarian cancer. In order to gain insight into the molecular structure of this protein, hK7 was crystallized after recombinant production in its folded and active form using a periplasmic secretion vector in Escherichia coli. The crystals belonged to the rhombohedral space group H32 and diffracted to 2.8 Å. The phase problem was solved by molecular replacement using the mouse kallikrein-related protein neuropsin. Completion of the model and structure refinement are under way.

  11. Determination of components of the plasma proteolytic enzyme systems gives information of prognostic value in patients with multiple trauma.

    Science.gov (United States)

    Aasen, A O; Kierulf, P; Vaage, J; Godal, H C; Aune, S

    1983-01-01

    Components of the plasma proteolytic enzyme systems were studied in 15 multiple trauma patients. There were 9 survivors and 6 fatal cases. All fatal cases had sepsis and/or post traumatic adult respiratory distress syndrome. Within the first day after trauma significantly reduced values were found for plasma prekallikrein (PKK), Hageman factor (HF) and Antithrombin III (AT III). In the survivors these parameters were normalized within the first five days after the injury. In the fatal cases, however, the same parameters remained reduced or declined during the observation period. The fatal cases also revealed a high frequency of positive ethanol gelation tests (EGT), elevated serum fibrin - fibrinogen degradation products (FDP) values and persisting low platelet counts. Analyses of plasma samples from both survivors and fatal cases, fractions by Sephadex G-150 gel filtration, demonstrated alpha 2-macroglobulin - plasma kallikrein complexes. These findings demonstrate activation of the kallikrein-kinin system as a part of pathological plasma proteolysis in multiple trauma patients. Persistent reductions of PKK, HF and AT III combined with positive EGT, elevated FDP values and reduced platelet counts indicate a poor prognosis.

  12. Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis.

    Science.gov (United States)

    Banerji, Aleena; Busse, Paula; Shennak, Mustafa; Lumry, William; Davis-Lorton, Mark; Wedner, Henry J; Jacobs, Joshua; Baker, James; Bernstein, Jonathan A; Lockey, Richard; Li, H Henry; Craig, Timothy; Cicardi, Marco; Riedl, Marc; Al-Ghazawi, Ahmad; Soo, Carolyn; Iarrobino, Ryan; Sexton, Daniel J; TenHoor, Christopher; Kenniston, Jon A; Faucette, Ryan; Still, J Gordon; Kushner, Harvey; Mensah, Robert; Stevens, Chris; Biedenkapp, Joseph C; Chyung, Yung; Adelman, Burt

    2017-02-23

    Background Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. Methods We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a 2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients), in two administrations 14 days apart. Patients assigned to lanadelumab were enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4 patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic profile of lanadelumab was assessed by measurement of plasma levels of cleaved high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and 400-mg groups as compared with the placebo group. Results No discontinuations occurred because of adverse events, serious adverse events, or deaths in patients who received lanadelumab. The most common adverse events that emerged during treatment were attacks of angioedema, injection-site pain, and headache. Dose-proportional increases in serum concentrations of lanadelumab were observed; the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma from patients with hereditary angioedema with C1 inhibitor deficiency to levels approaching that from patients without the disorder. From day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the placebo group. All

  13. The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito

    Science.gov (United States)

    In the past we have used the leucokinins, the kinins of the cockroach Leucophaea, to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using aedeskinins, the kinins of Aedes, are available, we find that in isolated Aede...

  14. Nucleotide sequence of cloned cDNA for human pancreatic kallikrein.

    Science.gov (United States)

    Fukushima, D; Kitamura, N; Nakanishi, S

    1985-12-31

    Cloned cDNA sequences for human pancreatic kallikrein have been isolated and determined by molecular cloning and sequence analysis. The identity between human pancreatic and urinary kallikreins is indicated by the complete coincidence between the amino acid sequence deduced from the cloned cDNA sequence and that reported partially for urinary kallikrein. The active enzyme form of the human pancreatic kallikrein consists of 238 amino acids and is preceded by a signal peptide and a profragment of 24 amino acids. A sequence comparison of this with other mammalian kallikreins indicates that key amino acid residues required for both serine protease activity and kallikrein-like cleavage specificity are retained in the human sequence, and residues corresponding to some external loops of the kallikrein diverge from other kallikreins. Analyses by RNA blot hybridization, primer extension, and S1 nuclease mapping indicate that the pancreatic kallikrein mRNA is also expressed in the kidney and sublingual gland, suggesting the active synthesis of urinary kallikrein in these tissues. Furthermore, the tissue-specific regulation of the expression of the members of the human kallikrein gene family has been discussed.

  15. Insect kinin analogs with cis-peptide bond motif 4-aminopyroglutamate: Optimal stereochemistry

    Science.gov (United States)

    The insect kinins are present in a wide variety of insects and function as potent diuretic peptides, though they are subject to rapid degradation by internal peptidases. Insect kinin analogs incorporating stereochemical variants of (2S,4S)-4-aminopyroglutamate (APy), a cis-peptide bond motif, demon...

  16. Plasma half-life and organ uptake ratio of radiolabeled glandular kallikrein in control and nephrectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, K.; Iwata, T.; Kokubu, T.

    1986-01-01

    The purified rat urinary kallikrein was radiolabeled by lactoperoxidase method and by chloramine T method. Plasma half-life of radiolabeled kallikrein was 5.06 +/- 0.59 (n = 5) min in control rats and 5.24 +/- 0.42 (n = 5) min in nephrectomized rats. There was no difference between two groups. From autoradiogram, main metabolic organs of radiolabeled kallikrein were liver, kidney and spleen. Total uptake of radiolabeled kallikrein in ech organ was the highest in liver (73.2%). The uptake per g tissue of radiolabeled kallikrein in each organ was high in liver (33.0%), kidney (31.4%) and spleen (21.1%). These results suggest that the active kallikrein is metabolized mainly in the liver, and kidney is not so an important organ to metabolize or to eliminate the active kallikrein in plasma. In order to clarify the mode of existence of active kallikrein in plasma, the following experiment was done by using disc gel electrophoresis. Radioactive profile of radiolabeled kallikrein showed one peak (Rf = 1.0), but radiolabeled kallikrein mixed with rat plasma showed two peaks, that is small peak (Rf = 1.0), and main peak (RF = 0.5). The most of radiolabeled kallikrein was bound to plasma protein and only five per cent was in free form. Furthermore, the binding of radiolabeled kallikrein to plasma protein was interfered by the addition of active kallikrein. These results suggest the possibility of existence of kallikrein binding protein in plasma.

  17. Unleashing the therapeutic potential of human kallikrein-related serine proteases.

    Science.gov (United States)

    Prassas, Ioannis; Eissa, Azza; Poda, Gennadiy; Diamandis, Eleftherios P

    2015-03-01

    Tissue kallikreins are a family of fifteen secreted serine proteases encoded by the largest protease gene cluster in the human genome. In the past decade, substantial progress has been made in characterizing the natural substrates, endogenous inhibitors and in vivo functions of kallikreins, and studies have delineated important pathophysiological roles for these proteases in a variety of tissues. Thus, kallikreins are now considered attractive targets for the development of novel therapeutics for airway, cardiovascular, tooth, brain, skin and neoplastic diseases. In this Review, we discuss recent advances in our understanding of the physiological functions and pathological implications of kallikrein proteases, and highlight progress in the identification of kallikrein inhibitors, which together are bringing us closer to therapeutically targeting kallikreins in selected disease settings.

  18. The Molecular Characterization of the Kinin Transcript and the Physiological Effects of Kinins in the Blood-Gorging Insect Rhodnius prolixus

    Science.gov (United States)

    The dramatic feeding-related activities of the Chagas' disease vector, Rhodnius prolixus are under neurohormonal regulation of serotonin and various neuropeptides. One such family of neuropeptides, the insect kinins, possess diuretic, digestive and myotropic activities in many insects. In this study...

  19. Calibrated kallikrein generation in human plasma

    DEFF Research Database (Denmark)

    Biltoft, D; Sidelmann, J J; Olsen, L F

    2016-01-01

    OBJECTIVES: The physiological role of the contact system remains inconclusive. No obvious clinical complications have been observed for factor XII (FXII), prekallikrein (PK), or high molecular weight kininogen deficiencies even though the contact system in vitro is associated with coagulation...

  20. Kinin Peptides Enhance Inflammatory and Oxidative Responses Promoting Apoptosis in a Parkinson’s Disease Cellular Model

    Directory of Open Access Journals (Sweden)

    Anna Niewiarowska-Sendo

    2016-01-01

    Full Text Available Kinin peptides ubiquitously occur in nervous tissue and participate in inflammatory processes associated with distinct neurological disorders. These substances have also been demonstrated to promote the oxidative stress. On the other hand, the importance of oxidative stress and inflammation has been emphasized in disorders that involve the neurodegenerative processes such as Parkinson’s disease (PD. A growing number of reports have demonstrated the increased expression of kinin receptors in neurodegenerative diseases. In this study, the effect of bradykinin and des-Arg10-kallidin, two representative kinin peptides, was analyzed with respect to inflammatory response and induction of oxidative stress in a PD cellular model, obtained after stimulation of differentiated SK-N-SH cells with a neurotoxin, 1-methyl-4-phenylpyridinium. Kinin peptides caused an increased cytokine release and enhanced production of reactive oxygen species and NO by cells. These changes were accompanied by a loss of cell viability and a greater activation of caspases involved in apoptosis progression. Moreover, the neurotoxin and kinin peptides altered the dopamine receptor 2 expression. Kinin receptor expression was also changed by the neurotoxin. These results suggest a mediatory role of kinin peptides in the development of neurodegeneration and may offer new possibilities for its regulation by using specific antagonists of kinin receptors.

  1. Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

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    Chong-Yu Zhang

    2015-02-01

    Full Text Available Recent evidence suggests that the human kallikrein 7 (KLK7 is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa and 92 with benign prostate hyperplasia (BPH were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57% benign cases showed positive staining for KLK7 and 23 of 116 (19.83% malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001. The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

  2. Kallikrein and Renin in the Membrane Fractions of the Rat Kidney.

    Science.gov (United States)

    1980-05-23

    and Renin _____ ___ i.;? - 2 SUMMARY Plasma membrane (P-H) and endoplasmic reticulum (ER) enriched fractions were isolated from the homogenized rat...The inhibitor of proteases, p-methylsulfonylfluoride inhibited 77-80% all kallikrein preparations at 3 w*1 concentration . Activation of renin Renin ...fold although only at a concentration 5-10 times higher than used with kallikrein. The relative rate of activation of renin in the ER fraction was

  3. Construction and Identification of Human Tissue Kallikrein Gene Eukaryotic Expressing Vector

    Institute of Scientific and Technical Information of China (English)

    DAI Yong; PENG Wujian; LI Tiyuan; DU Hong; SUN Wenxue; CHEN Deheng; XU Zhuojia

    2007-01-01

    To clone and sequence the human tissue kallikrein gene of Chinese, and to construct eukaryotic expression recombinant of KK, total RNA was extracted from human pancreas and human tissue kallikrein gene cDNA was amplified by PCR after reverse-transcription by using Oligo(dT)primer. The original kallikrein cDNA was recovered and filled with Klenow enzyme and inserted into KS plasmid. After restriction endonuclease digestion, KK cDNA was sequenced by ABI 377 analyzer.Then the KKgene was amplified from pBluescript KSKK and inserted into pcDNA3. A sequence comparison showed that the cloned kallikrein gene was only one nucleotide different from that reported in the Genbank. The coding amino acid was Asp in the Genbank gene, while the coding amino acid of Chinese kallikrein gene was Asn. The KK cDNA fragment was inserted into the eukaryotic expression vector pcDNA3. The cloned kallikrein gene and the pcDNA3KK can be used for further study in gene therapy...

  4. Copy number variants in the kallikrein gene cluster.

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    Pernilla Lindahl

    Full Text Available The kallikrein gene family (KLK1-KLK15 is the largest contiguous group of protease genes within the human genome and is associated with both risk and outcome of cancer and other diseases. We searched for copy number variants in all KLK genes using quantitative PCR analysis and analysis of inheritance patterns of single nucleotide polymorphisms. Two deletions were identified: one 2235-bp deletion in KLK9 present in 1.2% of alleles, and one 3394-bp deletion in KLK15 present in 4.0% of alleles. Each deletion eliminated one complete exon and created out-of-frame coding that eliminated the catalytic triad of the resulting truncated gene product, which therefore likely is a non-functional protein. Deletion breakpoints identified by DNA sequencing located the KLK9 deletion breakpoint to a long interspersed element (LINE repeated sequence, while the deletion in KLK15 is located in a single copy sequence. To search for an association between each deletion and risk of prostate cancer (PC, we analyzed a cohort of 667 biopsied men (266 PC cases and 401 men with no evidence of PC at biopsy using short deletion-specific PCR assays. There was no association between evidence of PC in this cohort and the presence of either gene deletion. Haplotyping revealed a single origin of each deletion, with most recent common ancestor estimates of 3000-8000 and 6000-14 000 years for the deletions in KLK9 and KLK15, respectively. The presence of the deletions on the same haplotypes in 1000 Genomes data of both European and African populations indicate an early origin of both deletions. The old age in combination with homozygous presence of loss-of-function variants suggests that some kallikrein-related peptidases have non-essential functions.

  5. Complement, Kinins, and Hereditary Angioedema: Mechanisms of Plasma Instability when C1 Inhibitor is Absent.

    Science.gov (United States)

    Kaplan, Allen P; Joseph, Kusumam

    2016-10-01

    Plasma of patients with types I and II hereditary angioedema is unstable if incubated in a plastic (i.e., inert) vessel at 37 °C manifested by progressively increasing formation of bradykinin. There is also a persistent low level of C4 in 95 % of patients even when they are symptomatic. These phenomena are due to the properties of the C1r subcomponent of C1, factor XII, and the bimolecular complex of prekallikrein with high molecular weight kininogen (HK). Purified C1r auto-activates in physiologic buffers, activates C1s, which in turn depletes C4. This occurs when C1 inhibitor is deficient. The complex of prekallikrein-HK acquires an inducible active site not present in prekallikrein which in Tris-type buffers cleaves HK stoichiometrically to release bradykinin, or in phosphate buffer auto-activates to generate kallikrein and bradykinin. Thus immunologic depletion of C1 inhibitor from factor XII-deficient plasma (phosphate is the natural buffer) auto-activates on incubation to release bradykinin. Normal C1 inhibitor prevents this from occurring. During attacks of angioedema, if factor XII auto-activates on surfaces, the initial factor XIIa formed converts prekallikrein to kallikrein, and kallikrein cleaves HK to release bradykinin. Kallikrein also rapidly activates most remaining factor XII to factor XIIa. Additional cleavages convert factor XIIa to factor XIIf and factor XIIf activates C1r enzymatically so that C4 levels approach zero, and C2 is depleted. There is also a possibility that kallikrein is generated first as a result of activation of the prekallikrein-HK complex by heat shock protein 90 released from endothelial cells, followed by kallikrein activation of factor XII.

  6. Activation of the kinin B1 receptor attenuates melanoma tumor growth and metastasis.

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    Patricia Dillenburg-Pilla

    Full Text Available Melanoma is a very aggressive tumor that does not respond well to standard therapeutic approaches, such as radio- and chemotherapies. Furthermore, acquiring the ability to metastasize in melanoma and many other tumor types is directly related to incurable disease. The B1 kinin receptor participates in a variety of cancer-related pathophysiological events, such as inflammation and angiogenesis. Therefore, we investigated whether this G protein-coupled receptor plays a role in tumor progression. We used a murine melanoma cell line that expresses the kinin B1 receptor and does not express the kinin B2 receptor to investigate the precise contribution of activation of the B1 receptor in tumor progression and correlated events using various in vitro and in vivo approaches. Activation of the kinin B1 receptor in the absence of B2 receptor inhibits cell migration in vitro and decreases tumor formation in vivo. Moreover, tumors formed from cells stimulated with B1-specific agonist showed several features of decreased aggressiveness, such as smaller size and infiltration of inflammatory cells within the tumor area, higher levels of pro-inflammatory cytokines implicated in the host anti-tumor immune response, lower number of cells undergoing mitosis, a poorer vascular network, no signs of invasion of surrounding tissues or metastasis and increased animal survival. Our findings reveal that activation of the kinin B1 receptor has a host protective role during murine melanoma tumor progression, suggesting that the B1 receptor could be a new anti-tumor GPCR and provide new opportunities for therapeutic targeting.

  7. Evolution of the plasma and tissue kallikreins, and their alternative splicing isoforms.

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    Vassiliki Lila Koumandou

    Full Text Available Kallikreins are secreted serine proteases with important roles in human physiology. Human plasma kallikrein, encoded by the KLKB1 gene on locus 4q34-35, functions in the blood coagulation pathway, and in regulating blood pressure. The human tissue kallikrein and kallikrein-related peptidases (KLKs have diverse expression patterns and physiological roles, including cancer-related processes such as cell growth regulation, angiogenesis, invasion, and metastasis. Prostate-specific antigen (PSA, the product of the KLK3 gene, is the most widely used biomarker in clinical practice today. A total of 15 KLKs are encoded by the largest contiguous cluster of protease genes in the human genome (19q13.3-13.4, which makes them ideal for evolutionary analysis of gene duplication events. Previous studies on the evolution of KLKs have traced mammalian homologs as well as a probable early origin of the family in aves, amphibia and reptilia. The aim of this study was to address the evolutionary and functional relationships between tissue KLKs and plasma kallikrein, and to examine the evolution of alternative splicing isoforms. Sequences of plasma and tissue kallikreins and their alternative transcripts were collected from the NCBI and Ensembl databases, and comprehensive phylogenetic analysis was performed by Bayesian as well as maximum likelihood methods. Plasma and tissue kallikreins exhibit high sequence similarity in the trypsin domain (>50%. Phylogenetic analysis indicates an early divergence of KLKB1, which groups closely with plasminogen, chymotrypsin, and complement factor D (CFD, in a monophyletic group distinct from trypsin and the tissue KLKs. Reconstruction of the earliest events leading to the diversification of the tissue KLKs is not well resolved, indicating rapid expansion in mammals. Alternative transcripts of each KLK gene show species-specific divergence, while examination of sequence conservation indicates that many annotated human KLK isoforms

  8. Kinin B1 receptors contributes to acute pain following minor surgery in humans

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    Brahim Jaime S

    2010-02-01

    Full Text Available Abstract Background Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the

  9. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  10. The Mosquito Aedes aegypti (L.) leucokinin Receptor is a Multiligand Receptor for the three Aedes kinins

    Science.gov (United States)

    2004-09-07

    peptide ( MNP ), probably a corticotropin- releasing factor-like peptide (diuresin), is released from the head (Petzel et al ., 1985, 1987). In the...meal (Petzel et al ., 1985). The MNP (and cAMP) regulates the transcellular transport of Na + while the Aedes kinins increase the...µl Superscript™ II reverse transcriptase (200 U). Reaction was mixed and incubated at 42 °C for 50 min. For enzyme inactivation incubation was at 70

  11. Deletion of Kinin B2 Receptor Alters Muscle Metabolism and Exercise Performance.

    Directory of Open Access Journals (Sweden)

    Felipe C G Reis

    Full Text Available Metabolic syndrome is a cluster of metabolic risk factors such as obesity, diabetes and cardiovascular diseases. Mitochondria is the main site of ATP production and its dysfunction leads to decreased oxidative phosphorylation, resulting in lipid accumulation and insulin resistance. Our group has demonstrated that kinins can modulate glucose and lipid metabolism as well as skeletal muscle mass. By using B2 receptor knockout mice (B2R-/- we investigated whether kinin action affects weight gain and physical performance of the animals. Our results show that B2R-/- mice are resistant to high fat diet-induced obesity, have higher glucose tolerance as well as increased mitochondrial mass. These features are accompanied by higher energy expenditure and a lower feed efficiency associated with an increase in the proportion of type I fibers and intermediary fibers characterized by higher mitochondrial content and increased expression of genes related to oxidative metabolism. Additionally, the increased percentage of oxidative skeletal muscle fibers and mitochondrial apparatus in B2R-/- mice is coupled with a higher aerobic exercise performance. Taken together, our data give support to the involvement of kinins in skeletal muscle fiber type distribution and muscle metabolism, which ultimately protects against fat-induced obesity and improves aerobic exercise performance.

  12. The inhibition of kallikrein-bradykinin pathway may be useful in the reduction of allergic reactions during honeybee venom immunotherapy

    Directory of Open Access Journals (Sweden)

    Ervin Ç. Mingomataj

    2009-05-01

    Full Text Available "nVenom immunotherapy (VIT protects patients with hymenoptera venom anaphylaxis from subsequent potentially life-threatening reactions. The most important side effects during VIT are systemic anaphylactic reactions (SAR, which are more prevalent during honeybee VIT. Despite the demonstrated diversity with regard to venom compounds, previous publications did not mention the plausible reason that can justify the difference of SAR frequency between honeybee and wasps. On the other hand, pre-treatment with H1-blocking antihistamines reduces the frequency and intensity of local and mild systemic anaphylactic reactions during VIT, but not appropriately moderate adverse reactions such as abdominal pain or angioedematous reactions, which can occur more prevalently also during honeybee VIT. In contrast to hymenoptera venom (HV anaphylaxis, these symptoms are very common during hereditary angioedema (HAE. In addition, in some patients who repeatedly experienced anaphylactic reactions during hyposensitization with HV are reported significantly lower renin, angiotensinogen I, and angiotensinogen II plasma levels. These facts may indicate that during honeybee VIT could be occurred a defective implication of renin-angiotensin system. This may be possible, because among hymenoptera, only the HV contains the antigen melittin, a potent kallikrein activator. These effects during honeybee VIT are similar to the HAE, because melittin-induced kallikrein activation on the first hand, as well as the implication of complement classical pathway during HAE on the second one, can lead both to increased bradykinin (BK secretion, plasma extravasation, and therefore to the occurrence of angioedema and abdominal symptoms. Consequently, the clinical effectiveness of BK receptor and generator blockers such as icatibant, ecallantide or NPC 18884, shown recently during the treatment of HAE attacks and acetic acid-induced abdominal constrictions in mice, may lead to the hypothesis

  13. The solution structure of the kallikrein-related peptidases inhibitor SPINK6

    NARCIS (Netherlands)

    Jung, Sascha; Fischer, Jan; Spudy, Björn; Kerkow, Tim; Sönnichsen, Frank D; Xue, Li; Bonvin, Alexandre M J J; Goettig, Peter; Magdolen, Viktor; Meyer-Hoffert, Ulf; Grötzinger, Joachim

    2016-01-01

    Kallikrein-related peptidases (KLKs) are crucial for epidermal barrier function and are involved in the proteolytic regulation of the desquamation process. Elevated KLK levels were reported in atopic dermatitis. In skin, the proteolytic activity of KLKs is regulated by specific inhibitors of the ser

  14. Yohimbine increases submaxillary kallikrein release into the saliva in dogs: evidence for alpha 2-adrenoceptor-mediated inhibition of cholinergic pathways.

    Science.gov (United States)

    Girolami, J. P.; Bascands, J. L.; Pécher, C.; Berlan, M.; Montastruc, J. L.; Montastruc, P.

    1991-01-01

    1. The effects of the alpha 2-adrenoceptor antagonist, yohimbine (0.5 mg kg-1, i.v.) on basal, sympathetic and parasympathetic stimulation-induced submaxillary kallikrein release were investigated in the anaesthetized dog. Kallikrein was measured by its kininogenase activity before and after trypsin activation which also allowed a study of the proportion of active to total enzyme. 2. Yohimbine induced a rapid, three fold increase in basal kallikrein release correlated with an increase in salivary flow rate which lasted for 60 min following injection. 3. Sectioning the chorda tympani did not affect basal kallikrein release but abolished yohimbine-induced rise in salivary kallikrein secretion. 4. Parasympathetic stimulation alone induced a 3 to 4 fold increase in basal kallikrein release correlated with an increase in salivary flow rate. Yohimbine induced a significant additional increase in parasympathetic-stimulated kallikrein release. 5. When the cervical sympathetic nerve was sectioned the basal kallikrein release decreased by 30 to 40%. 6. Sympathetic stimulation alone also induced a 3 to 4 fold increase in basal kallikrein. This was not correlated with the salivary flow and unaffected by yohimbine. 7. The results indicate that yohimbine increases submaxillary kallikrein release into the saliva by inhibition of presynaptic alpha 2-adrenoceptors located on the chorda tympani nerve endings. PMID:1849766

  15. A C-terminal Aldehyde Analog of the Insect Kinins Inhibits Diuresis in the Housefly

    Science.gov (United States)

    2006-09-21

    p e p t i d e s 2 8 ( 2 0 0 7 ) 1 4 6 – 1 5 2A C-terminal aldehyde analog of the insect kinins inhibits diuresis in the housefly Ronald J. Nachman a...secretion in crickets, but shows inhibition of both in vitro and in vivo diuresis in the housefly. R-LK-CHO reduced the total amount of urine voided over 3 h...to stimulate Malpighian tubule fluid secretion [2,25]. In the housefly, muscakinin has been implicated in the control of diuresis in response to

  16. Improvement of skin wound healing in diabetic mice by kinin B2 receptor blockade.

    Science.gov (United States)

    Desposito, Dorinne; Chollet, Catherine; Taveau, Christopher; Descamps, Vincent; Alhenc-Gelas, François; Roussel, Ronan; Bouby, Nadine; Waeckel, Ludovic

    2016-01-01

    Impaired skin wound healing is a major medical problem in diabetic subjects. Kinins exert a number of vascular and other actions limiting organ damage in ischaemia or diabetes, but their role in skin injury is unknown. We investigated, through pharmacological manipulation of bradykinin B1 and B2 receptors (B1R and B2R respectively), the role of kinins in wound healing in non-diabetic and diabetic mice. Using two mouse models of diabetes (streptozotocin-induced and db/db mice) and non-diabetic mice, we assessed the effect of kinin receptor activation or inhibition by subtype-selective pharmacological agonists (B1R and B2R) and antagonist (B2R) on healing of experimental skin wounds. We also studied effects of agonists and antagonist on keratinocytes and fibroblasts in vitro. Levels of Bdkrb1 (encoding B1R) and Bdkrb2 (encoding B2R) mRNAs increased 1-2-fold in healthy and wounded diabetic skin compared with in non-diabetic skin. Diabetes delayed wound healing. The B1R agonist had no effect on wound healing. In contrast, the B2R agonist impaired wound repair in both non-diabetic and diabetic mice, inducing skin disorganization and epidermis thickening. In vitro, B2R activation unbalanced fibroblast/keratinocyte proliferation and increased keratinocyte migration. These effects were abolished by co-administration of B2R antagonist. Interestingly, in the two mouse models of diabetes, the B2R antagonist administered alone normalized wound healing. This effect was associated with the induction of Ccl2 (encoding monocyte chemoattractant protein 1)/Tnf (encoding tumour necrosis factor α) mRNAs. Thus stimulation of kinin B2 receptor impairs skin wound healing in mice. B2R activation occurs in the diabetic skin and delays wound healing. B2R blockade improves skin wound healing in diabetic mice and is a potential therapeutic approach to diabetic ulcers. © 2016 Authors; published by Portland Press Limited.

  17. Development and applications of a radioimmunoassay to human plasma kallikrein; Desenvolvimento e aplicacoes de um radioimunoensaio para a calicreina plasmatica humana

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Roselane

    1986-12-31

    A radioimmunoassay to human plasma kallikrein (Hu PK) was developed using specific antibodies against the purified activates enzyme. The antiserum showed identity in the precipitation, double immuno-diffusion, immobility, immuno-electrophoresis, using as normal plasma as purified kallikrein. The protein {sup 125} I-kallikrein was prepared by chloramine-t method and presented homogeneity, stability, immunoactivity and high specific activity, so that a sensitive assay was assured. 193 refs., 19 figs., 4 tabs.

  18. Human plasma kallikrein and tissue kallikrein binding to a substrate based on the reactive site of a factor Xa inhibitor isolated from Bauhinia ungulata seeds.

    Science.gov (United States)

    Oliva, M L; Andrade, S A; Batista, I F; Sampaio, M U; Juliano, M; Fritz, H; Auerswald, E A; Sampaio, C A

    1999-12-01

    Kunitz type Bauhinia ungulata factor Xa inhibitor (BuXI) was purified from B. ungulata seeds. BuXI inactivates factor Xa and human plasma kallikrein (HuPK) with Ki values of 18.4 and 6.9 nM, respectively. However, Bauhinia variegata trypsin inhibitor (BvTI) which is 70% homologous to BuXI does not inhibit factor Xa and is less efficient on HuPK (Ki = 80 nM). The comparison between BuXI and BvTI reactive site structure indicates differences at Met59, Thr66 and Met67 residues. The hydrolysis rate of quenched fluorescence peptide substrates based on BuXI reactive site sequence, Abz-VMIAALPRTMFIQ-EDDnp (leading peptide), by HuPK and porcine pancreatic kallikrein (PoPK) is low, but hydrolysis is enhanced with Abz-VMIAALPRTMQ-EDDnp, derived from the leading peptide shortened by removing the dipeptide Phe-Ileu from the C-terminal portion, for HuPK (Km = 0.68 microM, k(cat)/Km = 1.3 x 10(6) M(-1) s(-1)), and the shorter substrate Abz-LPRTMQ-EDDnp is better for PoPK (Km = 0.66 microM, k(cat)/Km = 2.2 x 10(3) M(-1) s(-1)). The contribution of substrate methionine residues to HuPK and PoPK hydrolysis differs from that observed with factor Xa. The determined Km and k(cat) values suggest that the substrates interact with kallikreins the same as an enzyme and inhibitor interacts to form complexes.

  19. Kinin B2 receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE in mice

    Directory of Open Access Journals (Sweden)

    Bader Michael

    2008-11-01

    Full Text Available Abstract Background Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B1 and B2. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS, occurring not only in multiple sclerosis (MS but also in experimental autoimmune encephalomyelitis (EAE. We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. The aim of the present study was to evaluate the relevance of B2 receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG35–55-induced EAE in mice. Methods In order to evaluate the role of B2 receptor in the cerebral microvasculature we used wild-type (WT and kinin B2 receptor knockout (B2-/- mice subjected to MOG35–55-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B2-/- and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. The expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA. Results Clinical parameters of disease were reduced in B2-/- mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B2-/- mice when compared to WT. Conclusion Our results suggest that B2 receptors have two major effects in the control of EAE severity: (i B2 regulates the expression of chemokines, including CCL2 and CCL5, and (ii B2 modulates leukocyte recruitment and inflammatory lesions in the CNS.

  20. Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP.

    Science.gov (United States)

    Ottaiano, Tatiana F; Andrade, Sheila S; de Oliveira, Cleide; Silva, Mariana C C; Buri, Marcus V; Juliano, Maria A; Girão, Manoel J B C; Sampaio, Misako U; Schmaier, Alvin H; Wlodawer, Alexander; Maffei, Francisco H A; Oliva, Maria Luiza V

    2017-04-01

    Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin αIIbβ3 through interactions with the KGD/KGE sequence motif in huPK. Integrin αIIbβ3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS(473), ERK1/2, and p38 MAPK, and to Ca(2+) release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and αIIbβ3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  1. Biostable insect kinin analogs reduce blood meal and disrupt ecdysis in the blood-gorging Chagas’ disease vector, Rhodnius prolixus

    Science.gov (United States)

    Rhodnius prolixus is a blood-gorging hemipteran that takes blood meals that are approximately 10 times its body weight. This blood meal is crucial for growth and development and is needed to ensure a successful molt into the next instar. Kinins are a multifunctional family of neuropeptides which hav...

  2. Eco-Friendly Insecticide Discovery via Peptidomimetics: Design, Synthesis, and Aphicidal Activity of Novel Insect Kinin Analogues.

    Science.gov (United States)

    Zhang, Chuanliang; Qu, Yanyan; Wu, Xiaoqing; Song, Dunlun; Ling, Yun; Yang, Xinling

    2015-05-13

    Insect kinin neuropeptides are pleiotropic peptides that are involved in the regulation of hindgut contraction, diuresis, and digestive enzyme release. They share a common C-terminal pentapeptide sequence of Phe(1)-Xaa(2)-Yaa(3)-Trp(4)-Gly(5)-NH2 (where Xaa(2) = His, Asn, Phe, Ser, or Tyr; Yaa(3) = Pro, Ser, or Ala). Recently, the aphicidal activity of insect kinin analogues has attracted the attention of researchers. Our previous work demonstrated that the sequence-simplified insect kinin pentapeptide analogue Phe-Phe-[Aib]-Trp-Gly-NH2 could retain good aphicidal activity and be the lead compound for the further discovery of eco-friendly insecticides which encompassed a broad array of biochemicals derived from micro-organisms and other natural sources. Using the peptidomimetics strategy, we chose Phe-Phe-[Aib]-Trp-Gly-NH2 as the lead compound, and we designed and synthesized three series, including 31 novel insect kinin analogues. The aphicidal activity of the new analogues against soybean aphid was determined. The results showed that all of the analogues exhibited aphicidal activity. Of particular interest was the analogue II-1, which exhibited improved aphicidal activity with an LC50 of 0.019 mmol/L compared with the lead compound (LC50 = 0.045 mmol/L) or the commercial insecticide pymetrozine (LC50 = 0.034 mmol/L). This suggests that the analogue II-1 could be used as a new lead for the discovery of potential eco-friendly insecticides.

  3. The Single Kinin Receptor Signals to Separate and Independent Physiological Pathways in Malpighian Tubules of the Yellow Fever Mosquito

    Science.gov (United States)

    2010-06-10

    oscillations disappear in the presence of kinins (Fig. 2) which are known to activate nifedipine-sensitive Ca2+ channels in the basolateral membrane of...glycosylation sites of the rat luteinizing hormone receptor required for ligand binding. J Biol Chem 270: 21722-21728, 1995. 29 / 29 69. Zubrzak P

  4. Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice.

    Science.gov (United States)

    Grastilleur, Sébastien; Mouledous, Lionel; Bedel, Jerome; Etcheverry, Jonathan; Bader, Michael; Girolami, Jean-Pierre; Fourcade, Olivier; Frances, Bernard; Minville, Vincent

    2013-03-01

    Postoperative pain management is a clinical challenge that can be complicated by opioid-induced hyperalgesia (OIH). Kinin receptors could mediate both the acute and chronic phases of inflammation and pain. A few recent studies suggest that dynorphin A could maintain neuropathic pain by activating the bradykinin (BK) receptor. Thus, the effect of a single administration of sufentanil (a μ-opioid receptor agonist) was investigated in a model of carrageenan-induced inflammatory pain using three strains of mice, i.e., knockout mice for one kinin receptor, B1R or B2R (B1KO, B2KO), and wild-type C57/BL6J mice (WT) treated with either a B1R (R954) or a B2R antagonist (HOE140) or a KKS inhibitor (aprotinin). Pain was assessed and compared between the different groups using two behavioral tests exploring mechanical (von Frey filaments) and thermal (Hargreaves test) sensitivity. Pretreatment with sufentanil induced a sustained increase in pain sensitivity with a delayed return to baseline values characterizing an OIH in carrageenan-injected mice only. Sufentanil-induced OIH was not observed in B2KO but persisted in B1KO and was blunted by aprotinin and the B2R antagonist only. Collectively, our data indicate that the B2R receptor and BK synthesis or availability are essential peripheral steps in the mechanism leading to OIH in a pain context.

  5. Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Wille

    2001-01-01

    Full Text Available The present study was performed to: (a evaluate the effects of kinin B1 (Sar{D-Phe8}-des-Arg9-BK; 10 nmol/kg and B2 (bradykinin (BK; 10 nmol/kg receptor agonists on plasma extravasation in selected rat tissues; (b determine the contribution of a lipopolysaccharide (LPS (100 μ g/kg to the effects triggered by B1 and B2 agonists; and (c characterize the selectivity of B1 ({Leu8}desArg9-BK; 10 nmol/kg and B2 (HOE 140; 10 nmol/kg antagonists as inhibitors of this kinin-induced phenomenon. B1 and B2 agonists were shown to increase plasma extravasation in the duodenum, ileum and also in the urinary bladder of the rat. LPS pretreatment enhanced the plasma extravasation mediated only by the B1 agonist in the duodenum, ileum, trachea, main and segmentar bronchi. These effects were prevented by the B1. but not the B2 antagonist. In normal rats, the B2 antagonist inhibited the effect of B2 agonist in all the tissues analyzed. However, in LPS-treated rats, the B2 antagonist was ineffective in the urinary bladder.

  6. Captopril augments acetylcholine-induced bronchial smooth muscle contractions in vitro via kinin-dependent mechanisms.

    Science.gov (United States)

    Agrawal, Naman; Akella, Aparna; Deshpande, Shripad B

    2016-06-01

    Angiotensin converting enzyme (ACE) inhibitors therapy is aassociated with bothersome dry cough as an adverse effect. The mechanisms underlying this adverse effect are not clear. Therefore, influence of captopril (an ACE inhibitor) on acetylcholine (ACh)-induced bronchial smooth muscle contractions was investigated. Further, the mechanisms underlying the captopril-induced changes were also explored. In vitro contractions of rat bronchial smooth muscle to cumulative concentrations of ACh were recorded before and after exposure to captopril. Further, the involvement of kinin and inositol triphosphate (IP₃) pathways for captopril-induced alterations were explored. ACh produced concentration-dependent (5-500 µM) increase in bronchial smooth muscle contractions. Pre-treatment with captopril augmented the ACh-induced contractions at each concentration significantly. Pre-treatment with aprotinin (kinin synthesis inhibitor) or heparin (inositol triphosphate, IP₃-inhibitor), blocked the captopril-induced augmentation of bronchial smooth muscle contractions evoked by ACh. Further, captopril-induced augmentation was absent in calcium-free medium. These results suggest that captopril sensitizes bronchial smooth muscles to ACh-induced contractions. This sensitization may be responsible for dry cough associated with captopril therapy.

  7. Differential regulation of collagen secretion by kinin receptors in cardiac fibroblast and myofibroblast

    Energy Technology Data Exchange (ETDEWEB)

    Catalán, Mabel; Smolic, Christian [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Contreras, Ariel [Instituto Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile (Chile); Ayala, Pedro; Olmedo, Ivonne; Copaja, Miguel; Boza, Pía; Vivar, Raúl; Avalos, Yennifer [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Lavandero, Sergio [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Instituto Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile (Chile); Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX (United States); Velarde, Victoria [Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago (Chile); Díaz-Araya, Guillermo, E-mail: gadiaz@ciq.uchile.cl [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile)

    2012-06-15

    Kinins mediate their cellular effects through B1 (B1R) and B2 (B2R) receptors, and the activation of B2R reduces collagen synthesis in cardiac fibroblasts (CF). However, the question of whether B1R and/or B2R have a role in cardiac myofibroblasts remains unanswered. Methods: CF were isolated from neonate rats and myofibroblasts were generated by an 84 h treatment with TGF-β1 (CMF). B1R was evaluated by western blot, immunocytochemistry and radioligand assay; B2R, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and cyclooxygenases 1and 2 (COX-1, and COX-2) were evaluated by western blot; intracellular Ca{sup +2} levels were evaluated with Fluo-4AM; collagen secretion was measured in the culture media using the picrosirius red assay kit. Results: B2R, iNOS, COX-1 and low levels of B1R but not eNOS, were detected by western blot in CF. Also, B1R, B2R, and COX-2 but not iNOS, eNOS or COX-1, were detected by western blot in CMF. By immunocytochemistry, our results showed lower intracellular B1R levels in CF and higher B1R levels in CMF, mainly localized on the cell membrane. Additionally, we found B1R only in CMF cellular membrane through radioligand displacement assay. Bradykinin (BK) B2R agonist increased intracellular Ca{sup 2+} levels and reduced collagen secretion both in CF and CMF. These effects were blocked by HOE-140, and inhibited by L-NAME, 1400W and indomethacin. Des-Arg-kallidin (DAKD) B1R agonist did not increase intracellular Ca{sup 2+} levels in CF; however, after preincubation for 1 h with DAKD and re-stimulation with the same agonist, we found a low increase in intracellular Ca{sup 2+} levels. Finally, DAKD increased intracellular Ca{sup 2+} levels and decreased collagen secretion in CMF, being this effect blocked by the B1R antagonist des-Arg9-Leu8-kallidin and indomethacin, but not by L-NAME or 1400 W. Conclusion: B1R, B2R, iNOS and COX-1 were expressed differently between CF and CMF, and collagen secretion was

  8. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.

    Science.gov (United States)

    Hofman, Zonne L M; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C Erik

    2016-08-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. However, several observations in patients with HAE are difficult to explain from a pathogenic model claiming a local activation process at the site of the angioedema attack. Therefore we postulate an alternative model for angioedema attacks in patients with HAE, which assumes a systemic, fluid-phase activation of the contact system to generate BK and its breakdown products. Interaction of these peptides with endothelial receptors that are locally expressed in the affected tissues rather than with receptors constitutively expressed by the endothelium throughout the whole body explains that such a systemic activation process results in local manifestations of an attack. In particular, BK receptor 1, which is induced on the endothelium by inflammatory stimuli, such as kinins and cytokines, meets the specifications of the involved receptor. The pathogenic model discussed here also provides an explanation for why angioedema can occur at multiple sites during an attack and why HAE attacks respond well to modest increases of circulating C1INH activity levels because inhibition of fluid-phase Factor XIIa and kallikrein requires lower C1INH levels than inhibition of activator-bound factors.

  9. The angiotensin II type 1 receptor antagonist Losartan binds and activates bradykinin B2 receptor signaling

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Olsen, Kristine Boisen; Erikstrup, Niels;

    2011-01-01

    The angiotensin II type 1 receptor (AT1R) blocker (ARB) Losartan has cardioprotective effects during ischemia-reperfusion injury and inhibits reperfusion arrhythmias -effects that go beyond the benefits of lowering blood pressure. The renin-angiotensin and kallikrein-kinin systems are intricately...

  10. Panicolytic-like action of bradykinin in the dorsal periaqueductal gray through μ-opioid and B2-kinin receptors.

    Science.gov (United States)

    Sestile, Caio César; Maraschin, Jhonatan Christian; Gama, Vanessa Scalco; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida

    2017-09-01

    A wealth of evidence has shown that opioid and kinin systems may control proximal defense in the dorsal periaqueductal gray matter (dPAG), a critical panic-associated area. Studies with drugs that interfere with serotonin-mediated neurotransmission suggest that the μ-opioid receptor (MOR) synergistically interacts with the 5-HT1A receptor in the dPAG to inhibit escape, a panic-related behavior. A similar inhibitory effect has also been reported after local administration of bradykinin (BK), which is blocked by the non-selective opioid receptor antagonist naloxone. The latter evidence, points to an interaction between BK and opioids in the dPAG. We further explored the existence of this interaction through the dPAG electrical stimulation model of panic. We also investigated whether intra-dPAG injection of captopril, an inhibitor of the angiotensin-converting enzyme (ACE) that also degrades BK, causes a panicolytic-like effect. Our results showed that intra-dPAG injection of BK inhibited escape performance in a dose-dependent way, and this panicolytic-like effect was blocked by the BK type 2 receptor (B2R) antagonist HOE-140, and by the selective MOR antagonist CTOP. Conversely, the panicolytic-like effect caused by local administration of the selective MOR agonist DAMGO was antagonized by pre-treatment with either CTOP or HOE-140, indicating cross-antagonism between MOR and B2R. Finally, intra-dPAG injection of captopril also impaired escape in a dose-dependent way, and this panicolytic-like effect was blocked by pretreatment with HOE-140, suggesting mediation by endogenous BK. The panicolytic-like effect of captopril indicates that the use of ACE inhibitors in the clinical management of panic disorder may be worth exploring. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Caveolin-1-Mediated Expression and Secretion of Kallikrein 6 in Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Rebecca S. Henkhaus

    2008-02-01

    Full Text Available Kallikreins are secreted proteases that may play a functional role and/or serve as a serum biomarker for the presence or progression of certain types of cancers. Kallikrein 6 (KLK6 has been shown to be upregulated in several types of cancers, including colon. The aims of this study were to elucidate pathways that influence KLK6 gene expression and KLK6 protein secretion in the HCT116 human colon cancer cells. Our data indicate a central role for caveolin-1 (CAV-1, the main structural protein of caveolae, in both KLK6 gene expression and protein secretion. Sucrose gradient subcellular fractionation reveals that CAV-1 and KLK6 colocalize to lipid raft domains in the plasma membrane of HCT116 cells. Furthermore, we show that CAV-1, although it does not directly interact with the KLK6 molecule, enhances KLK6 secretion from the cells. Deactivation of CAV-1, through SRC-mediated phosphorylation, decreased KLK6 secretion. We also demonstrate that, in colon cancer cells, CAV-1 increased the amount of phosphorylated AKT in cells by inhibiting the activity of the AKT-negative regulators PP1 and PP2A. This study demonstrates that proteins such as CAV-1 and AKT, which are known to be altered in colon cancer, affect KLK6 expression and KLK6 secretion.

  12. Evaluation of human tissue kallikrein-related peptidases 6 and 10 expression in early gastroesophageal adenocarcinoma.

    Science.gov (United States)

    Grin, Andrea; Samaan, Sara; Tripathi, Monika; Rotondo, Fabio; Kovacs, Kalman; Bassily, Mena N; Yousef, George M

    2015-04-01

    Kallikreins are a family of serine proteases that are linked to malignancy of different body organs with potential clinical utility as tumor markers. In this study, we investigated kallikrein-related peptidase 6 (KLK6) and KLK10 expression in early gastroesophageal junction adenocarcinoma and Barrett esophagus (BE) with and without dysplasia. Immunohistochemistry revealed significantly increased KLK6 expression in early invasive cancer compared with dysplastic (P = .009) and nondysplastic BE (P = .0002). There was a stepwise expression increase from metaplasia to dysplasia and invasive tumors. Significantly higher KLK10 was seen in dysplastic lesions compared with metaplasia but not between dysplastic lesions and invasive cancers. KLK6 staining intensity was increased at the invasive front (P = .006), suggesting its role in tumor invasiveness. Neither KLK6 nor KLK10 was significantly associated with other prognostic markers, including depth of invasion, indicating their potential as independent biomarkers. Our results should be interpreted with caution due to limited sample size. There was a significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect. We then compared KLK6 and KLK10 messenger RNA expression between metaplastic and cancerous tissues in an independent data set of esophageal carcinoma from The Cancer Genome Atlas. KLK6 and KLK10 may be useful markers and potential therapeutic targets in gastroesophageal junction tumors.

  13. Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses.

    Directory of Open Access Journals (Sweden)

    Ana Carolina Monteiro

    2007-11-01

    Full Text Available Although the concept that dendritic cells (DCs recognize pathogens through the engagement of Toll-like receptors is widely accepted, we recently suggested that immature DCs might sense kinin-releasing strains of Trypanosoma cruzi through the triggering of G-protein-coupled bradykinin B2 receptors (B2R. Here we report that C57BL/6.B2R-/- mice infected intraperitoneally with T. cruzi display higher parasitemia and mortality rates as compared to B2R+/+ mice. qRT-PCR revealed a 5-fold increase in T. cruzi DNA (14 d post-infection [p.i.] in B2R-/- heart, while spleen parasitism was negligible in both mice strains. Analysis of recall responses (14 d p.i. showed high and comparable frequencies of IFN-gamma-producing CD4+ and CD8+ T cells in the spleen of B2R-/- and wild-type mice. However, production of IFN-gamma by effector T cells isolated from B2R-/- heart was significantly reduced as compared with wild-type mice. As the infection continued, wild-type mice presented IFN-gamma-producing (CD4+CD44+ and CD8+CD44+ T cells both in the spleen and heart while B2R-/- mice showed negligible frequencies of such activated T cells. Furthermore, the collapse of type-1 immune responses in B2R-/- mice was linked to upregulated secretion of IL-17 and TNF-alpha by antigen-responsive CD4+ T cells. In vitro analysis of tissue culture trypomastigote interaction with splenic CD11c+ DCs indicated that DC maturation (IL-12, CD40, and CD86 is controlled by the kinin/B2R pathway. Further, systemic injection of trypomastigotes induced IL-12 production by CD11c+ DCs isolated from B2R+/+ spleen, but not by DCs from B2R-/- mice. Notably, adoptive transfer of B2R+/+ CD11c+ DCs (intravenously into B2R-/- mice rendered them resistant to acute challenge, rescued development of type-1 immunity, and repressed TH17 responses. Collectively, our results demonstrate that activation of B2R, a DC sensor of endogenous maturation signals, is critically required for development of acquired

  14. Tickling stimulation causes the up-regulation of the kallikrein family in the submandibular gland of the rat.

    Science.gov (United States)

    Yamamuro, Takuya; Hori, Miyo; Nakagawa, Yoshimi; Hayashi, Takashi; Sakamoto, Shigeko; Ohnishi, Junji; Takeuchi, Shino; Mihara, Yuko; Shiga, Takashi; Murakami, Kazuo; Urayama, Osamu

    2013-01-01

    We recently showed that tactile stimulation (tickling) accompanied by positive emotion altered the expression of many genes in the rat hypothalamus (Hori et al., 2009 [15]). In this study, the effect of repeated tickling on gene expressions of the rat salivary gland was examined. After 4-week stimulation, several genes of the kallikrein (Klk) family were remarkably up-regulated and the alpha-amylase (amylase) gene was down-regulated in DNA microarray analysis. In quantitative analysis using real-time PCR of the submandibular gland of the rats tickled for 2 weeks, mRNAs of Klk1, Klk2 (Klk1c2, Tonin), Klk7 (Klk1l), Klk1b3 (Nerve growth factor, gamma), Klk1c10, Klks3 (Klk1c9) and GK11 were significantly 2-5-fold increased among 18 members of the Klk gene family examined and the submandibular amylase was decreased compared with the lightly touched and untouched control rats. In immunoblot analysis the increase in Klk7 protein was observed in the whole cell lysate fraction of the submandibular gland. In immunohistochemical analysis with anti-Klk7 polyclonal antibody, the immunostain was increased in duct cells of the submandibular gland of the tickled rat when compared with the lightly touched and untouched control rats. These results suggest that tactile sensory processing in the central nervous system affects the gene expression in the peripheral tissue probably via hormonal and/or autonomic neural activities. Submandibular Klks may be biochemical markers indicating positive emotional states.

  15. Vascular angiotensin II type 2 receptor attenuates atherosclerosis via a kinin/NO-dependent mechanism.

    Science.gov (United States)

    Takata, Hiroki; Yamada, Hiroyuki; Kawahito, Hiroyuki; Kishida, Sou; Irie, Daisuke; Kato, Taku; Wakana, Noriyuki; Miyagawa, Sonoko; Fukui, Kensuke; Matsubara, Hiroaki

    2015-06-01

    The angiotensin II (Ang II) type 1 receptor exerts pro-atherogenic action by augmenting oxidative stress, whereas the Ang II type 2 receptor (AT2)-mediated effect on atherosclerosis remains controversial. AT2 transgenic (AT2-Tg) mice, which overexpress AT2 in their vascular smooth muscle cells, were crossed with apoE-deficient (apoE(-/-)) mice to generate AT2 transgenic apoE(-/-) mice (AT2-Tg/apoE(-/-)). A subpressor dose of Ang II infusion exaggerated atherosclerosis development in apoE(-/-) mice, which was markedly suppressed in AT2-Tg/apoE(-/-) mice. Inhibitors of nitric oxide (NO) synthase (L-NAME) or bradykinin type 2 receptor completely abolished AT2-mediated anti-atherogenic actions. The vascular cell adhesion molecule-1 expression levels and degree of monocyte/macrophage accumulation in the intima were also considerably reduced in AT2-Tg/apoE(-/-) mice; these phenomena were completely reversed by L-NAME treatment. Ang II infusion significantly enhanced the accumulation of dihydroethidium-positive mononuclear cells in the intima and mRNA expression levels of Nox2, a phagocytic cell-type NADPH oxidase subunit in apoE(-/-) mice, which was completely inhibited in AT2-Tg/apoE(-/-) mice. Vascular AT2 stimulation exerts anti-atherogenic actions in an endothelial kinin/NO-dependent manner, and its anti-oxidative effect is likely to be exerted by inhibiting the accumulation of superoxide-producing mononuclear leukocytes. © The Author(s) 2013.

  16. Effect of pancreatic kallikrein combined with magnesium sulfate therapy on disease severity of patients with severe preeclampsia

    Institute of Scientific and Technical Information of China (English)

    Yi Yang

    2016-01-01

    Objective:To study the clinical effect of pancreatic kallikrein combined with magnesium sulfate therapy on severe preeclampsia.Methods: A total of 47 patients with severe preeclampsia treated in our hospital from May 2013 to October 2015 were retrospectively analyzed, patients who received pancreatic kallikrein combined with magnesium sulfate therapy were selected as observation group, patients who received magnesium sulfate therapy were selected as control group, and then blood pressure level, renal function, uterine artery and umbilical artery blood flow state, and hypoxia indexes in serum and placenta were compared between two groups.Results: After treatment, systolic pressure and diastolic pressure levels as well as serum CysC level and 24 h urine protein level of observation group were significantly lower than those of control group, the uterine artery and umbilical artery S/D and PI were significantly lower than those of control group, PIGF and NO levels in serum as well as Xiap and Survivin levels in placenta were significantly higher than those of control group, and sVEGFR1 level in serum as well as Caspase-3 and Caspase-7 levels in placenta was significantly lower than those of control group.Conclusions:Pancreatic kallikrein combined with magnesium sulfate therapy can alleviate the disease severity, lower blood pressure and vascular resistance, and improve renal function and the apoptosis caused by placental hypoxia in patients with severe preeclampsia.

  17. Induction of salivary kallikreins by the diet containing a sweet-suppressive peptide, gurmarin, in the rat.

    Science.gov (United States)

    Yamada, Ayako; Nakamura, Yuki; Sugita, Daigo; Shirosaki, Shinya; Ohkuri, Tadahiro; Katsukawa, Hideo; Nonaka, Kazuaki; Imoto, Toshiaki; Ninomiya, Yuzo

    2006-07-28

    Gymnema sylvestre (gymnema) contains gurmarin that selectively inhibits responses to sweet substances in rodents. The present study investigated possible interaction between gurmarin and the submandibular saliva in rats fed diet containing gymnema. Electrophoretic analyses demonstrated that relative amounts of two proteins in the saliva clearly increased in rats fed the gymnema diet. However, rats previously given section of the bilateral glossopharyngeal nerve showed no such salivary protein induction. Analyses of amino acid sequence indicate that two proteins are rat kallikrein 2 (rK2) and rat kallikrein 9 (rK9). rK2 and rK9, a family of serine proteases, have a striking resemblance of cleavage site in the protein substrates. Interestingly, gurmarin possesses comparable residues with those rK2 and rK9 prefer. The kallikreins significantly inhibited immunoreaction between gurmarin and antigurmarin antiserum. These results suggest that rK2 and rK9 increased by chemosensory information for the gymnema diet via the glossopharyngeal nerve might cleave gurmarin or at least cause specific binding with it.

  18. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

    Science.gov (United States)

    Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

    2014-05-01

    The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis.

  19. Kinin B1 receptor antagonists inhibit diabetes-induced hyperalgesia in mice.

    Science.gov (United States)

    Gabra, Bichoy H; Sirois, Pierre

    2003-02-01

    Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with vascular permeability changes leading to many complications including nephropathy, retinopathy, neuropathy, hypertension and hyperalgesia. The bradykinin B(1) receptors (BKB(1)-R) were recently found to be upregulated alongside the development of type 1 diabetes and to be involved in its complications. Kinins are important mediators of a variety of biological effects including cardiovascular homeostasis, inflammation and nociception. In the present study, we studied the effect of a selective BKB(1)-R agonist desArg(9)-BK (DBK) and two selective receptor antagonists, the R-715 (Ac-Lys-[D-beta Nal(7), Ile(8)] desArg(9)-BK) and the R-954 (Ac-Orn-[Oic(2), alphaMe Phe(5), D-beta Nal(7), Ile(8)] desArg(9)-BK) on diabetic hyperalgesia. Type 1 diabetes was induced in male CD-1 mice via a single injection of streptozotocin (STZ, 200mg/kg, i.p.), one week before the test. Nociception, a measure of hyperalgesia, was assessed using the plantar stimulation (Hargreaves) and the tail-immersion tests. The induction of type 1 diabetes provoked a significant hyperalgesic activity in diabetic mice, causing an 11% decrease in plantar stimulation reaction time and 13% decrease in tail-immersion reaction time, compared to normal mice. Following acute administration of R-715 (100-600 microg/kg, i.p.), or R-954 (50-400 microg/kg, i.p.), the STZ-induced hyperalgesic activity was blocked in a dose-dependent manner and the hot plate and tail-immersion latencies of diabetic mice returned to normal values observed in control healthy mice. In addition, the acute administration of DBK (400 microg/kg, i.p.) significantly potentiated diabetes-induced hyperalgesia, an effect that was totally reversed by R-715 (1.6-2.4 mg/kg, i.p.) and R-954 (0.8-1.2mg/kg, i.p.). These results provide further evidence for the implication of the BKB(1)-R in type 1 diabetic hyperalgesia and suggest a novel

  20. Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

    Directory of Open Access Journals (Sweden)

    Talbot Sébastien

    2012-01-01

    Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p

  1. Recombinant adeno-associated virus-mediated human kallikrein gene therapy protects against hypertensive target organ injuries through inhibiting cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jiang-tao YAN; Tao WANG; Dao-wen WANG

    2009-01-01

    Aim: Overexpression of human tissue kallikrein (HK), mediated by recombinant adeno-associated virus (rAAV), decreased blood pres-sure in spontaneous hypertensive rats (SHRs) and reduced injury to the heart, aorta and kidney. In this study, we used both an in vivo animal model and in vitro cell culture system to investigate whether rAAV-rnediated HK gene therapy protects against organ damage by inhibiting cell apoptosis. Methods: rAAV encoding HK(rAAV-HK) or LacZ(rAAV-lacZ) were delivered as a control to spontaneously hypertensive rats (SHRs) and cultured human embryonic kidney (HEK) 293 cells. Results: Treatment with rAAV-HK decreased cell apoptosis in the target organs of SHRs and also inhibited lipopolysaccharide (LPS)-in-duced HEK 293 apoptosis. The rAAV-HK delivery system also increased the levels of apoptosis-inhibiting proteins bcl-2 and bcl-x_L, and decreased the level of Bax and the activity of caspase 3, two promoters of apoptosis. In addition to its role in the inhibition of apopto-sis, rAAV-HK also activated the cell survival and proliferation signaling pathways ERK1/2 and PI3K/AKT. Conclusion: rAAV-mediated HK gene delivery has multiple therapeutic possibilities for treating hypertension, not only by decreasing blood pressure, but also by directly inhibiting end-organ damage.

  2. Increased anxiety-like behavior in neuropsin (kallikrein-related peptidase 8) gene-deficient mice.

    Science.gov (United States)

    Horii, Yoichiro; Yamasaki, Nobuyuki; Miyakawa, Tsuyoshi; Shiosaka, Sadao

    2008-06-01

    Neuropsin (kallikrein-related peptidase 8) is concentrated in the hippocampus, amygdala, olfactory bulb, and prefrontal cortex. Earlier studies showed that protease deficiency causes a significant impairment of early-phase long-term potentiation in the Schaffer collateral pathway and hippocampus-dependent memory in the Y maze and Morris water maze (Z. Chen et al., 1995; A. Hirata et al., 2001; H. Tamura et al., 2006). In addition to neuropsin's participation in the hippocampal memory, amygdalar and cortical localization of the gene suggests extrahippocampal behavioral function, and the authors therefore examined neuropsin-deficient mice, including tests of sensory motor reflex, open field, light-dark transition, Rota-Rod, elevated plus-maze, hot plate, startle response-prepulse inhibition, Porsolt forced swim, Barnes maze, eight-arm radial maze, and contextual and cued fear conditioning tests. Here, the authors found increased anxiety in neuropsin-deficient mice, suggesting the involvement of this protease in emotional responses. (Copyright) 2008 APA, all rights reserved.

  3. Functional characterization of the human-specific (type Ⅱ)form of kallikrein 8, a gene involved in learning and memory

    Institute of Scientific and Technical Information of China (English)

    Zhi-xiang Lu; Qin Huang; Bing Su

    2009-01-01

    Kallikrein 8 (KLK8) is a serine protease functioning in the central nervous system, and essential in many aspects of neuronal activities. Sequence comparison and gene expression analysis among diverse primate species identified a human-specific splice form of KLK8 (type Ⅱ) with preferential expression in the human brain, which may contribute to the origin of human cognition. To gain insights into the physiological and biochemical role of this novel form, we conducted functional analyses of human type Ⅱ KLK8. Our results show that type Ⅱ KLK8 is abundantly expressed in human embryonic stem cells and in embryo brain samples, suggesting a potential role in embryogenesis. There are dramatic expression variations in different individuals and brain regions, which is a reflection of its dynamic role in neural activities. Furthermore, the transcription start site (TSS) of KLK8 is tissue-specific, with a brain-specific TSS found in humans indicating functional specialization. Our in vitro biochemical assay shows that there is a type Ⅱspecific intermediate protein form, although the processed end-point enzymes are the same for both type I and type ⅡKLK8, suggesting that the emergence of type 11 KLK8 in the human brain likely leads to functional modifications of KLK8.

  4. B2-kinin receptors in the dorsal periaqueductal gray are implicated in the panicolytic-like effect of opiorphin.

    Science.gov (United States)

    Sestile, Caio César; Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Santana, Rosangela Getirana; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida

    2017-08-07

    Reported results have shown that the pentapeptide opiorphin inhibits oligopeptidases that degrade brain neuropeptides, and has analgesic and antidepressant effects in experimental animals, without either tolerance or dependency after chronic administration. In a previous study we showed that opiorphin has a panicolytic-like effect in the dorsal periaqueductal gray (dPAG) electrical stimulation test (EST), mediated by the μ-opioid receptor (MOR). This study further analyzes the mechanism of opiorphin panicolytic action, using the EST and drug injection inside the dPAG. The obtained results showed that blockade of the 5-HT1A receptors with WAY-100635 did not change the escape-impairing effect of opiorphin, and combined injection of sub-effective doses of opiorphin and the 5-HT1A-agonist 8-OH-DPAT did not have a significant anti-escape effect. In contrast, the anti-escape effect of opiorphin was antagonized by pretreatment with the kinin B2 receptor blocker HOE-140, and association of sub-effective doses of opiorphin and bradykinin caused a significant anti-escape effect. The anti-escape effect of bradykinin was not affected by previous administration of WAY-100635. Therefore, the anti-escape effect of opiorphin in the dPAG seems to be mediated by endogenous bradykinin, acting on kinin B2 receptors, which previous results have shown to interact synergistically with MOR in the dPAG to restrain escape in two animal models of panic. Chemical compounds: Opiorphin (PubChem CID: 25195667); WAY100635 maleate salt (PubChem CID: 11957721); 8-OH-DPAT hydrobromide (PubChem CID: 6917794); Bradykinin (PubChem CID: 439201); HOE-140 (Icatibant) (PubChem CID: 6918173). Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The efficacy of pancreatic kallikrein treatment of early-onset preeclampsia and which impact of patient D-dimmer

    Institute of Scientific and Technical Information of China (English)

    Ying Yu; Min Liu

    2015-01-01

    Objective: To analyze the pancreatic kallikrein treatment of early-onset preeclampsia therapeutic effect and impact on patients D-dimer. Methods: 94 cases of early-onset pre-eclampsia patients were divided into the control group and the observation group. In the control group patients were treated with magnesium sulfate treatment. In the observation group patients were treated with pancreatic kallikrein based on the control group use of common treatment. Results: After treatment, D-dimer levels in serum in the observation group patients were lower than that of the control group, significant differences (P<0.01). After treatment, 24 h urine protein, random urine protein/creatinine ratio in urine in the observation group patients were lower than that of the control group, significant differences (P<0.01). The incidence of severe neonatal asphyxia was 4.26% in the observation group patients were lower than that of the control group was 29.79%, significant differences (P<0.01). After treatment, Pregnancy was prolonged (12.43±4.31) days, gestational age newborns (35.84±2.71) weeks, birth weight (2 564.21±507.19) g in the observation group patients were higher than that of the control group, significant differences (P<0.01). Conclusions: Pancreatic kallikrein treatment of early-onset preeclampsia can effectively improve the treatment, ameliorate the hypercoagulable state and renal function of the patients’ blood, extend the number of days of pregnancy, and reduce the incidence of severe neonatal asphyxia.

  6. Blood biomarker levels to aid discovery of cancer-related single-nucleotide polymorphisms: kallikreins and prostate cancer.

    Science.gov (United States)

    Klein, Robert J; Halldén, Christer; Cronin, Angel M; Ploner, Alexander; Wiklund, Fredrik; Bjartell, Anders S; Stattin, Pär; Xu, Jianfeng; Scardino, Peter T; Offit, Kenneth; Vickers, Andrew J; Grönberg, Henrik; Lilja, Hans

    2010-05-01

    Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding beta-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis that included sequencing of all coding, flanking, and 2 kb of putative promoter regions of all 15 kallikrein (KLK) genes spanning approximately 280 kb on chromosome 19q, we identified novel single-nucleotide polymorphisms (SNP) and genotyped 104 SNPs in 1,419 cancer cases and 736 controls in Cancer Prostate in Sweden 1, with independent replication in 1,267 cases and 901 controls in Cancer Prostate in Sweden 2. This verified prior associations of SNPs in KLK2 and in MSMB (but not in KLK3) with prostate cancer. Twelve SNPs in KLK2 and KLK3 were associated with levels of PSA forms or hK2 in plasma of control subjects. Based on our comprehensive approach, this is likely to represent all common KLK variants associated with these phenotypes. A T allele at rs198977 in KLK2 was associated with increased cancer risk and a striking decrease of hK2 levels in blood. We also found a strong interaction between rs198977 genotype and hK2 levels in blood in predicting cancer risk. Based on this strong association, we developed a model for predicting prostate cancer risk from standard biomarkers, rs198977 genotype, and rs198977 x hK2 interaction; this model had greater accuracy than did biomarkers alone (area under the receiver operating characteristic curve, 0.874 versus 0.866), providing proof in principle to clinical application for our findings.

  7. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...

  8. Kallikrein 4 and matrix metalloproteinase-20 immunoexpression in malignant, benign and infiltrative odontogenic tumors

    Science.gov (United States)

    Crivelini, Marcelo Macedo; Oliveira, Denise Tostes; de Mesquita, Ricardo Alves; de Sousa, Suzana Cantanhede Orsini Machado; Loyola, Adriano Motta

    2016-01-01

    Context: Matrix metalloproteinase-20 (MMP20) (enamelysin) and kallikrein 4 (KLK4) are enzymes secreted by ameloblasts that play an important role in enamel matrix degradation during amelogenesis. However, studies have shown that neoplastic cells can produce such enzymes, which may affect the tumor infiltrative and metastatic behaviors. Aims: The aim of this study is to assess the biological role of MMP20 and KLK4 in odontogenic tumors. Materials and Methods: The enzymes were analyzed immunohistochemically in ameloblastoma, adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor, keratocystic odontogenic tumor with or without recurrence and odontogenic carcinoma. Statistical Analysis Used: Clinicopathological parameters were statistically correlated with protein expression using the Fisher's exact test. Kruskal–Wallis and Wilcoxon-independent methods were used to evaluate the differences in median values. Results: Positive Immunoexpression was detected in all benign lesions, with a prevalence of 75–100% immunolabeled cells. Patients were predominantly young, Caucasian, female, with slow-growing tumors located in the mandible causing asymptomatic swelling. No KLK4 expression was seen in carcinomas, and the amount of MMP20-positive cells varied between 20% and 80%. Rapid evolution, recurrence and age >60 years characterized the malignant nature of these lesions. Conclusions: Data showed that KLK4 and MMP20 enzymes may not be crucial to tumoral infiltrative capacity, especially in malignant tumors, considering the diversity and peculiarity of these lesions. The significant immunoexpression in benign lesions, remarkably in AOT, is likely associated with differentiated tumor cells that can produce and degrade enamel matrix-like substances. This would be expected since the histogenesis of odontogenic tumors commonly comes from epithelium that recently performed a secretory activity in tooth formation. PMID:27601817

  9. Up-regulation and clinical significance of serine protease kallikrein 6 in colon cancer.

    Science.gov (United States)

    Kim, Jong-Tae; Song, Eun Young; Chung, Kyung-Sook; Kang, Min Ah; Kim, Jae Wha; Kim, Sang Jick; Yeom, Young Il; Kim, Joo Heon; Kim, Kyo Hyun; Lee, Hee Gu

    2011-06-15

    Kallikrein-related peptidase 6 (KLK6) encodes a trypsin-like serine protease that is up-regulated in several cancers, although the putative functions of KLK6 in cancer have not been elucidated. In the current study, overexpression of KLK6 was identified in colon cancer, and the possibility that KLK6 may be a suitable candidate as a tumor marker was examined. Messenger RNA (mRNA) transcript levels and protein up-regulation of KLK6 in colon cancer tissues was examined using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and clinicopathologic analyses. Cell proliferation, invasiveness, and antiapoptotic activity were determined in colon cancer cells that were transfected with small-interfering RNA (siRNA) of KLK6. KLK6 mRNA was up-regulated significantly in tumor tissues compared with nontumor regions. KLK6 protein was strongly expressed in adenocarcinomas but was not expressed in normal mucosa or in premalignant dysplastic lesions. Sera from patients with colon cancer revealed an increase in KLK6 secretion (0.25 μg/mL; P = .031) compared with noncancer cells (0.19 μg/mL). Clinicopathologic and immunohistochemical studies of 143 patients with colon cancer revealed a significant correlation between KLK6 expression and Dukes disease stage (P = .005). High KLK6 expression was associated significantly with shorter overall (P = .001) and recurrence-free survival (P = .001). The rates of proliferation and invasiveness were decreased by 50% in cells that were transfected with KLK6 siRNA. The overexpression of KLK6 led to decreased activity of the E-cadherin promoter. KLK6 was up-regulated significantly in tissues and sera from patients with colon cancer and was associated closely with a poor prognosis, suggesting that KLK6 may be used as a potential biomarker and a therapeutic target for colon cancer. Copyright © 2010 American Cancer Society.

  10. Quantification of Human Kallikrein-Related Peptidases in Biological Fluids by Multiplatform Targeted Mass Spectrometry Assays.

    Science.gov (United States)

    Karakosta, Theano D; Soosaipillai, Antoninus; Diamandis, Eleftherios P; Batruch, Ihor; Drabovich, Andrei P

    2016-09-01

    Human kallikrein-related peptidases (KLKs) are a group of 15 secreted serine proteases encoded by the largest contiguous cluster of protease genes in the human genome. KLKs are involved in coordination of numerous physiological functions including regulation of blood pressure, neuronal plasticity, skin desquamation, and semen liquefaction, and thus represent promising diagnostic and therapeutic targets. Until now, quantification of KLKs in biological and clinical samples was accomplished by enzyme-linked immunosorbent assays (ELISA). Here, we developed multiplex targeted mass spectrometry assays for the simultaneous quantification of all 15 KLKs. Proteotypic peptides for each KLK were carefully selected based on experimental data and multiplexed in single assays. Performance of assays was evaluated using three different mass spectrometry platforms including triple quadrupole, quadrupole-ion trap, and quadrupole-orbitrap instruments. Heavy isotope-labeled synthetic peptides with a quantifying tag were used for absolute quantification of KLKs in sweat, cervico-vaginal fluid, seminal plasma, and blood serum, with limits of detection ranging from 5 to 500 ng/ml. Analytical performance of assays was evaluated by measuring endogenous KLKs in relevant biological fluids, and results were compared with selected ELISAs. The multiplex targeted proteomic assays were demonstrated to be accurate, reproducible, sensitive, and specific alternatives to antibody-based assays. Finally, KLK4, a highly prostate-specific protein and a speculated biomarker of prostate cancer, was unambiguously detected and quantified by immunoenrichment-SRM assay in seminal plasma and blood serum samples from individuals with confirmed prostate cancer and negative biopsy. Mass spectrometry revealed exclusively the presence of a secreted isoform and thus unequivocally resolved earlier disputes about KLK4 identity in seminal plasma. Measurements of KLK4 in either 41 seminal plasma or 58 blood serum samples

  11. Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Chong-Yu Zhang; Yu Zhu; Wen-Bin Rui; Jun Dai; Zhou-Jun Shen

    2015-01-01

    Recent evidence suggests that the human kallikrein 7 (KLK7) is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein‑related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa) and 92 with benign prostate hyperplasia (BPH) were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT‑PCR) and western blot, kallikrein‑related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein‑related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57%) benign cases showed positive staining for KLK7 and 23 of 116 (19.83%) malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001). The expression level of kallikrein‑related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein‑related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein‑related peptidase 7 and KLK7 expression are down‑regulated in PCa and lower expression of kallikrein‑related peptidase 7 closely correlates with higher Gleason score and higher prostate‑specific antigen level.

  12. Highly sensitive automated chemiluminometric assay for measuring free human glandular kallikrein-2.

    Science.gov (United States)

    Klee, G G; Goodmanson, M K; Jacobsen, S J; Young, C Y; Finlay, J A; Rittenhouse, H G; Wolfert, R L; Tindall, D J

    1999-06-01

    Human glandular kallikrein (hK2) is a serine protease that has 79% amino acid identity with prostate-specific antigen (PSA). Both free hK2 and hK2 complexed to alpha1-antichymotrypsin (ACT) are present in the blood in low concentrations. We wished to measure hK2 in serum with limited contribution from hK2-ACT for the results. We developed an automated assay for hK2 with use of a select pair of monoclonal antibodies. The prototype assay was implemented on a Beckman Coulter ACCESS(R) analyzer. The detection limit of the assay was 1.5 ng/L, the "functional sensitivity" (day-to-day CV <15%) was <4 ng/L, cross-reactivity with PSA and PSA-ACT was negligible, and cross-reactivity with hK2-ACT was 2%. After surgical removal of prostate glands, serum hK2 was <7 ng/L and was <15 ng/L in most healthy women. The median serum concentration of hK2 in healthy men without prostate cancer was 26 ng/L. The median concentration of hK2 was 72 ng/L for men having prostate cancer with lower Gleason scores compared with 116 ng/L for men with more advanced cancer. The concentration of hK2 correlated weakly with PSA, with the mean hK2 concentrations generally 30- to 80-fold lower than PSA concentrations. The availability of a robust, high sensitivity automated assay for hK2 should facilitate further investigations of the role of hK2 measurements in the management of patients with prostate disease.

  13. The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Cannell, Elizabeth; Dornan, Anthony J.; Halberg, Kenneth Agerlin

    2016-01-01

    (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate...... that suppression of DH44 signalling improves desiccation tolerance of the intact fly. Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule......-specific LKR, suggesting interactions between DH44 and LK signalling pathways. Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also...

  14. The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster.

    Science.gov (United States)

    Cannell, Elizabeth; Dornan, Anthony J; Halberg, Kenneth A; Terhzaz, Selim; Dow, Julian A T; Davies, Shireen-A

    2016-06-01

    Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly. Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule-specific LKR, suggesting interactions between DH44 and LK signalling pathways. Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also, Malpighian tubule stellate cell-specific knockdown of LKR significantly reduced starvation tolerance, demonstrating a role for neuropeptide signalling during starvation stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. [Diagnosis of hereditary angioedema].

    Science.gov (United States)

    Bouillet, Laurence

    2015-01-01

    Hereditary angioedema is a rare disease, potentially life-threatening. It requires a specific treatment. Angioedema without wheals associated with abdominal attacks are very specific of this disease. Antigenemy and functional C1Inhibitor assays are necessary for the diagnosis. The hereditary angioedema with normal C1Inh (type III) is a diagnostic challenge. Bradykinin, secondary to kallikrein-kinin system activation is the key mediator of hereditary angioedema. Female are more symptomatic. Attacks can be induced by menstruations, pregnancies or contraceptive pills.

  16. Digestion of atopic allergens with trypsin α-chymotrypsin and pancreatic kallikrein, and influence of the allergens upon the proteolytic and esterolytic activity of these enzymes

    NARCIS (Netherlands)

    Berrens, L.

    1968-01-01

    The action of bovine trypsin, α-chymotrypsin and pancreatic kallikrein upon a number of atopic allergens has been studied by pH-stat measurements during short-term incubation. Most atopic allergens proved chemically resistant towards these enzymes. Graphs of enzyme susceptibility vs. the ratio of ex

  17. Synthetic peptides and fluorogenic substrates related to the reactive site sequence of Kunitz-type inhibitors isolated from Bauhinia: interaction with human plasma kallikrein.

    Science.gov (United States)

    Oliva, M L; Santomauro-Vaz, E M; Andrade, S A; Juliano, M A; Pott, V J; Sampaio, M U; Sampaio, C A

    2001-01-01

    We have previously described Kunitz-type serine proteinase inhibitors purified from Bauhinia seeds. Human plasma kallikrein shows different susceptibility to those inhibitors. In this communication, we describe the interaction of human plasma kallikrein with fluorogenic and non-fluorogenic peptides based on the Bauhinia inhibitors' reactive site. The hydrolysis of the substrate based on the B. variegata inhibitor reactive site sequence, Abz-VVISALPRSVFIQ-EDDnp (Km 1.42 microM, kcat 0.06 s(-1), and kcat/Km 4.23 x 10(4) M(-1) s(-1)), is more favorable than that of Abz-VMIAALPRTMFIQ-EDDnp, related to the B. ungulata sequence (Km 0.43 microM, kcat 0.00017 s(-1), and kcat/Km 3.9 x 10(2) M(-1) s(-1)). Human plasma kallikrein does not hydrolyze the substrates Abz-RPGLPVRFESPL-EDDnp and Abz-FESPLRINIIKE-EDDnp based on the B. bauhinioides inhibitor reactive site sequence, the most effective inhibitor of the enzyme. These peptides are competitive inhibitors with Ki values in the nM range. The synthetic peptide containing 19 amino acids based on the B. bauhinioides inhibitor reactive site (RPGLPVRFESPL) is poorly cleaved by kallikrein. The given substrates are highly specific for trypsin and chymotrypsin hydrolysis. Other serine proteinases such as factor Xa, factor XII, thrombin and plasmin do not hydrolyze B. bauhinioides inhibitor related substrates.

  18. Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    List, K; Jensen, Ole Nørregaard; Bugge, T H;

    2000-01-01

    kallikrein). The pro-uPA converting activity of the mGK-6 enzyme, as well as its ability to cleave a synthetic substrate for glandular kallikrein, was inhibited by the serine proteinase inhibitor leupeptin but not by other serine proteinase inhibitors such as aprotinin, antithrombin III, or alpha(1...... the cascade by activating pro-uPA. The urine from Plg -/- mice contained active two-chain uPA as well as a proteinase capable of activating exogenously added pro-uPA. The active component was purified and identified by mass spectrometry-based peptide mapping as mouse glandular kallikrein mGK-6 (true tissue...

  19. Kallikrein-8 Proteolytically Processes Human Papillomaviruses in the Extracellular Space To Facilitate Entry into Host Cells

    Science.gov (United States)

    Cerqueira, Carla; Samperio Ventayol, Pilar; Vogeley, Christian

    2015-01-01

    ABSTRACT The entry of human papillomaviruses into host cells is a complex process. It involves conformational changes at the cell surface, receptor switching, internalization by a novel endocytic mechanism, uncoating in endosomes, trafficking of a subviral complex to the Golgi complex, and nuclear entry during mitosis. Here, we addressed how the stabilizing contacts in the capsid of human papillomavirus 16 (HPV16) may be reversed to allow uncoating of the viral genome. Using biochemical and cell-biological analyses, we determined that the major capsid protein L1 underwent proteolytic cleavage during entry. In addition to a dispensable cathepsin-mediated proteolysis that occurred likely after removal of capsomers from the subviral complex in endosomes, at least two further proteolytic cleavages of L1 were observed, one of which was independent of the low-pH environment of endosomes. This cleavage occurred extracellularly. Further analysis showed that the responsible protease was the secreted trypsin-like serine protease kallikrein-8 (KLK8) involved in epidermal homeostasis and wound healing. Required for infection, the cleavage was facilitated by prior interaction of viral particles with heparan sulfate proteoglycans. KLK8-mediated cleavage was crucial for further conformational changes exposing an important epitope of the minor capsid protein L2. Occurring independently of cyclophilins and of furin that mediate L2 exposure, KLK8-mediated cleavage of L1 likely facilitated access to L2, located in the capsid lumen, and potentially uncoating. Since HPV6 and HPV18 also required KLK8 for entry, we propose that the KLK8-dependent entry step is conserved. IMPORTANCE Our analysis of the proteolytic processing of incoming HPV16, an etiological agent of cervical cancer, demonstrated that the capsid is cleaved extracellularly by a serine protease active during wound healing and that this cleavage was crucial for infection. The cleavage of L1 is one of at least four structural

  20. Pulmonary oedema producing toxin from Mesobuthus tamulus venom augments cardio-respiratory reflexes through B2 kinin receptors.

    Science.gov (United States)

    Alex, Anitha B; Akella, Aparna; Tiwari, Anil K; Deshpande, Shripad B

    2014-01-01

    The current study was undertaken to compare the effects of pulmonary oedema producing toxin (PO-Tx) isolated from Mesobuthus tamulus venom on cardio-respiratory reflexes with exogenously administered bradykinin (BK) and to delineate the type of BK receptors mediating these responses. Jugular venous injection of phenyldiguanide (PDG) in anaesthetized rats produced reflex bradycardia, hypotension and apnoea. The PDG-induced reflex was augmented (two folds) by PO-Tx. The pulmonary water content in PO-Tx treated group was also increased. The PO-Tx-induced reflex changes as well as pulmonary oedema were blocked by-Hoe-140 implicating the involvement of B2 kinin receptors. Exogenous BK also produced augmentation (two folds) of the PDG-induced reflexes and increased the pulmonary water content. The BK-induced augmentation was blocked by pre-treatment with des-Arg10 Hoe 140 (a B1 receptor antagonist) and Hoe 140 (B2 receptor antagonist). However, these antagonists did not prevent the development of BK-induced pulmonary oedema. Present results indicate that PO-Tx augmented the PDG-induced reflex responses similar to BK and the PO-Tx induced augmentation of reflexes is mediated through B2 receptors.

  1. Activity of human kallikrein-related peptidase 6 (KLK6) on substrates containing sequences of basic amino acids. Is it a processing protease?

    Science.gov (United States)

    Silva, Roberta N; Oliveira, Lilian C G; Parise, Carolina B; Oliveira, Juliana R; Severino, Beatrice; Corvino, Angela; di Vaio, Paola; Temussi, Piero A; Caliendo, Giuseppe; Santagada, Vincenzo; Juliano, Luiz; Juliano, Maria A

    2017-05-01

    Human kallikrein 6 (KLK6) is highly expressed in the central nervous system and with elevated level in demyelinating disease. KLK6 has a very restricted specificity for arginine (R) and hydrolyses myelin basic protein, protein activator receptors and human ionotropic glutamate receptor subunits. Here we report a previously unreported activity of KLK6 on peptides containing clusters of basic amino acids, as in synthetic fluorogenic peptidyl-Arg-7-amino-4-carbamoylmethylcoumarin (peptidyl-ACC) peptides and FRET peptides in the format of Abz-peptidyl-Q-EDDnp (where Abz=ortho-aminobenzoic acid and Q-EDDnp=glutaminyl-N-(2,4-dinitrophenyl) ethylenediamine), in which pairs or sequences of basic amino acids (R or K) were introduced. Surprisingly, KLK6 hydrolyzed the fluorogenic peptides Bz-A-R(↓)R-ACC and Z-R(↓)R-MCA between the two R groups, resulting in non-fluorescent products. FRET peptides containing furin processing sequences of human MMP-14, nerve growth factor (NGF), Neurotrophin-3 (NT-3) and Neurotrophin-4 (NT-4) were cleaved by KLK6 at the same position expected by furin. Finally, KLK6 cleaved FRET peptides derived from human proenkephalin after the KR, the more frequent basic residues flanking enkephalins in human proenkephalin sequence. This result suggests the ability of KLK6 to release enkephalin from proenkephalin precursors and resembles furin a canonical processing proteolytic enzyme. Molecular models of peptides were built into the KLK6 structure and the marked preference of the cut between the two R of the examined peptides was related to the extended conformation of the substrates. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Roles of kallikrein-2 biomarkers (free-hK2 and pro-hK2 for predicting prostate cancer progression-free survival

    Directory of Open Access Journals (Sweden)

    Anatilde Gonzalez Guerrico

    2017-07-01

    Full Text Available Free human kallikrein 2 (free-hK2 and hK2 pro-form (pro-hK2 have been found to be increased in tumor tissues and serum from patients with prostate cancer. We established semiautomatic assays for free-hK2 and pro-hK2 using a research version of the Beckman Coulter ACCESS2 system. Serum samples from a cohort of 189 men undergoing radical prostatectomy for known high-risk disease were assayed for Prostate-Specific Antigen (PSA, free-PSA, free-hK2, and pro-hK2. Univariate Cox regression and multivariate models were used to predict both Gleason scores and progression-free survival (PFS. Free-hk2 levels ≥80 ng/L were predictive of both Gleason scores ≥7 ( p = 0.04 and PFS ( p = 0.03. PSA ≥8.0 µg/L also was predictive of PFS ( p = 0.02. However, neither % free-PSA nor pro-hK2, when treated as continuous or cutoff variables were associated with Gleason score or PFS. Multivariable models showed that clinical stage T1c versus T2/T3, Gleason score ≥7, and PSA ≥8.0 µg/L or clinical stage T1c versus T2/T3, Gleason scores ≥7, and free-hK2 ≥80 ng/L were among the best models predicting PFS. Both free-hK2 and PSA in conjunction with clinical stage and Gleason score are good predictors of PFS in prostate cancer.

  3. Human kallikrein 5 as a novel prognostic biomarker for triple-negative breast cancer: tissue expression analysis and relationship with disease course.

    Science.gov (United States)

    Yang, F; Li, J Y; Yin, Q N; Yang, K; Dong, S N; Bai, L J; Liu, P; Tong, X W

    2015-08-14

    The purposes of this study were to analyze the expression and distribution of human kallikrein 5 (hK5) in triple-negative breast cancer (TNBC) tissues, to establish a standard operating procedure (SOP) for its immunohistochemical assay, and to evaluate the possibility of hK5 being a prognostic biomarker for TNBC. Recombinant hK5 protein and specific antibody were prepared, and the expression and distribution of hK5 in TNBC tissues were detected using immunohistochemistry. An SOP for immunohistochemical staining of hK5 in TNBC tissues was established to allow automatic staining under optimized conditions. The resulting images were digitized for evaluation and statistical analysis via a human scoring system. Our results showed that expression of hK5 protein could predict the progression of TNBC. Pearson's chi-square test results showed that high hK5 expression in tumor stromal cells was significantly correlated with distal metastasis (P = 0.039). A high staining score for lymphocyte infiltration in tumor stroma was significantly correlated with low histological grade of tumor (P = 0.025). Univariate and multivariate Cox regression analyses verified that the staining score for hK5 in tumor stromal cells may be a biomarker for poor prognosis in TNBC patients (univariate HR = 2.289, 95%CI = 1.362-3.848, P = 0.002; multivariate HR = 2.105, 95%CI = 1.189-3.727, P = 0.011). In conclusion, the expression level of hK5 in tumor stromal cells is a promising biomarker for poor prognosis in TNBC. Patients with high histological grade are more prone to distal metastasis and aggressive tumor progression.

  4. Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model.

    Directory of Open Access Journals (Sweden)

    David Pépin

    Full Text Available Human tissue kallikreins (KLKs are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, little is known about the contributions of KLK5, 6 and 10 to ovarian cancer pathophysiology.In this study, a panel of 13 human ovarian cancer cell lines was screened by ELISA for secretion of KLK5, 6, 8, 10, 13, and 14. The ES-2 cell line, devoid of these kallikreins, was transfected with expression vectors of KLK5, 6 and 10 individually or in pairs. Co-expression of KLK5, 6 and 10 was correlated with lessened aggressivity of ovarian cancer cell lines as defined by reduced colony formation in soft agar and tumorigenicity in nude mice. ES-2 clones overexpressing KLK5, 10/5, 10/6, 5/6 made significantly fewer colonies in soft agar. When compared to control mice, survival of mice injected with ES-2 clones overexpressing KLK10, 10/5, 10/6, 5/6 was significantly longer, while KLK6 was shorter. All groups displaying a survival advantage also differed quantitatively and qualitatively in their presentation of ascites, with both a reduced incidence of ascites and an absence of cellular aggregates within those ascites. The survival advantage conferred by KLK10 overexpression could be recapitulated with the exogenous administration of a recombinant KLK10. In conclusion, these findings indicate that KLK5, 6 and 10 may modulate the progression of ovarian cancer, and interact together to alter tumour pathophysiology. Furthermore, results support the putative role of KLK10 as a tumour suppressor and suggest it may hold therapeutic potential in ovarian cancer.

  5. Effects on peritoneal proteolysis and hemodynamics by high doses of methyl-prednisolone in experimental acute pancreatitis.

    Science.gov (United States)

    Ruud, T E; Aasen, A O; Røise, O; Lium, B; Pillgram-Larsen, J; Stadaas, J O

    1986-01-01

    Acute pancreatitis was induced in 15 anesthetized pigs by injection of Na-taurocholate into the pancreatic duct. Seven animals were pretreated with methyl-prednisolone sodium succinate 30 mg/kg intravenously. Using chromogenic peptide substrate assays, values of trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and arterial pressure (AP) were regularly monitored before and during a six hour observation period. In acute untreated pancreatitis a 40% reduction of PKK levels was found paralleled by an increased KK activity and a reduction of KKI capacity. High TRY levels were found in several animals. The mortality rate was 63%. The pretreated animals all survived. CO and AP were significantly less reduced than in the untreated animals. Components of the plasma kallikrein-kinin system and TRY in the exudate remained mainly unchanged. Methyl-prednisolone given as pretreatment significantly improves hemodynamic parameters and increases the survival rate. Methyl-prednisolone suppresses generation of trypsin activity and activation of the plasma kallikrein-kinin system in the peritoneal exudate which may be of significant importance to the outcome.

  6. Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer

    DEFF Research Database (Denmark)

    Ulmert, David; Vickers, Andrew J; Scher, Howard I

    2012-01-01

    The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase...... of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon(®)), a novel GnRH antagonist....

  7. A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden

    Directory of Open Access Journals (Sweden)

    Scardino Peter T

    2008-07-01

    Full Text Available Abstract Background Prostate-specific antigen (PSA is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2 could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model and age, PSA and digital rectal exam (the 'clinical' model were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57% and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy.

  8. Tissue Kallikrein Reverses Insulin Resistance and Attenuates Nephropathy in Diabetic Rats by Activation of PI3 kinase/Akt and AMPK Signaling Pathways

    OpenAIRE

    Yuan, Gang; Deng, Juanjuan; Wang, Tao; Zhao, Chunxia; Xu, Xizheng; Wang, Peihua; Voltz, James W.; Edin, Matthew L.; Xiao, Xiao; Chao, Lee; Chao, Julie; Zhang, Xin A.; Zeldin, Darryl C.; Wang, Dao Wen

    2007-01-01

    We previously reported that intravenous delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. In the current study, we evaluated the potential of a recombinant adeno-associated viral vector expressing the HK cDNA (rAAV·HK) as a sole, long term therapy to correct insulin resistance and prevent renal damage in streptozotocin-induced type-2 diabetic rats. Administration of streptozotocin i...

  9. Clinical significance of human kallikrein 12 gene expression in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    En-Hao Zhao; Zhi-Yong Shen; Hua Liu; Xin Jin; Hui Cao

    2012-01-01

    AIM:To investigate whether the expression of kallikrein 12 (KLK12) is related to the development of gastric cancer (GC) and to determine the role of KLK12 in gastric cancer cells growth,invasion and migration.METHODS:Between September 2007 and March 2008,133 patients with histologically confirmed GC were recruited for the study.Expression of KLK12 was detected in samples from GC patients by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry.The relationship between KLK12 protein expression and clinicopathological features of GC was analyzed.The difference in 5-year survival rates between the high KLK12 protein expression group and the low KLK12 expression group was compared.Additionally,the expression of KLK12 was examined in various human GC cell lines,including MKN-28,SGC-7901 and MKN-45.Small interfering RNA (siRNA) was used to inhibit KLK12 expression in MKN-45 cells.Cell clones stably transfected with KLK12 siRNA were tested for KLK12 expression by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting.Furthermore,a series of functional assays were performed in this study to assess the biological features of transfected cells.Cell proliferation was assessed using the methylthiazolyltetrazoliumassay.Finally,cell migration and invasion were assessed using transwell chamber assays.RESULTS:Of the 133 GC patients induded in the study,126 (94.7%) showed a higher expression level of KLK12 mRNA when compared to noncancerous tissue specimens.Expression of KLK12 mRNA was significantly higher in GC tissues than in normal tissue (P < 0.001).KLK12 protein expression was detected in 96 of 133 (72.2%) GC samples with moderate or strong staining primarily in the cytoplasm.In contrast,negative immunostaining for KLK12 protein was observed in the corresponding normal gastric mucosal tissue.Overexpression of KLK12 protein was significantly associated with lymph node metastasis (P =0

  10. Kallikrein-Related Peptidase 5 Contributes to H3N2 Influenza Virus Infection in Human Lungs.

    Science.gov (United States)

    Magnen, Mélia; Gueugnon, Fabien; Guillon, Antoine; Baranek, Thomas; Thibault, Virginie C; Petit-Courty, Agnès; de Veer, Simon J; Harris, Jonathan; Humbles, Alison A; Si-Tahar, Mustapha; Courty, Yves

    2017-08-15

    Hemagglutinin (HA) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating HAs of seasonal influenza A viruses (IAVs) in humans. This study focuses on human KLK1 and KLK5, 2 of the 15 serine proteases known as the kallikrein-related peptidases (KLKs). We find that their mRNA expression in primary human bronchial cells is stimulated by IAV infection. Both enzymes cleaved recombinant HA from several strains of the H1 and/or H3 virus subtype in vitro, but only KLK5 promoted the infectivity of A/Puerto Rico/8/34 (H1N1) and A/Scotland/20/74 (H3N2) virions in MDCK cells. We assessed the ability of treated viruses to initiate influenza in mice. The nasal instillation of only the KLK5-treated virus resulted in weight loss and lethal outcomes. The secretion of this protease in the human lower respiratory tract is enhanced during influenza. Moreover, we show that pretreatment of airway secretions with a KLK5-selective inhibitor significantly reduced the activation of influenza A/Scotland/20/74 virions, providing further evidence of its importance. Differently, increased KLK1 secretion appeared to be associated with the recruitment of inflammatory cells in human airways regardless of the origin of inflammation. Thus, our findings point to the involvement of KLK5 in the proteolytic activation and spread of seasonal influenza viruses in humans.IMPORTANCE Influenza A viruses (IAVs) cause acute infection of the respiratory tract that affects millions of people during seasonal outbreaks every year. Cleavage of the hemagglutinin precursor by host proteases is a critical step in the life cycle of these viruses. Consequently, host proteases that activate HA can be considered promising targets for the development of new antivirals

  11. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice.

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    Martins-Olivera, Bruno Tadeu; Almeida-Reis, Rafael; Theodoro-Júnior, Osmar Aparecido; Oliva, Leandro Vilela; Neto Dos Santos Nunes, Natalia; Olivo, Clarice Rosa; Vilela de Brito, Marlon; Prado, Carla Máximo; Leick, Edna Aparecida; Martins, Mílton de Arruda; Oliva, Maria Luiza Vilela; Righetti, Renato Fraga; Tibério, Iolanda de Fátima Lopes Calvo

    2016-01-01

    Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD). However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI) to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group) or saline (SAL group) and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups). At day 28, the following analyses were performed: (I) lung mechanics, (II) exhaled nitric oxide (ENO), (III) bronchoalveolar lavage fluid (BALF), and (IV) lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

  12. Regulation of acid-sensing ion channel 1a function by tissue kallikrein may be through channel cleavage.

    Science.gov (United States)

    Su, Jingjing; Tang, Yuping; Liu, Ling; Zhou, Houguang; Dong, Qiang

    2011-02-18

    Recently, we have demonstrated that serine protease tissue kallikrein (TK) can protect cortical neurons against ischemia-acidosis/reperfusion-induced injury, and that this effect might be mediated by acid-sensing ion channels (ASICs). However, little is known about how TK regulates the function of ASICs. Here we provided evidence that the regulation of ASIC1a function by TK was probably correlated with its cleavage. High concentration of TK (3μM) partially cleaved the extracellular loop of ASIC1a, followed by a marked decrease of LDH release and an increase of cell survival at pH 6.2. Pretreatment with a protease inhibitor aprotinin inhibited the cleavage of ASIC1a and prevented functional regulation by TK. However, the cleavage of ASIC2a, which was not functionally modified by TK, was not observed. Therefore, we propose that the limited proteolysis of extracellular loop within ASIC1a might be one of the potential regulatory mechanisms of ASIC1a function by TK. © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Kallikrein 4 and amelogenesis imperfecta%激肽释放酶4与釉质发生不全

    Institute of Scientific and Technical Information of China (English)

    王光平; 李明霞; 刘建国

    2013-01-01

      激肽释放酶4(KLK4)在釉质发生的转换期和成熟早期大量表达,水解基质蛋白,降低牙釉蛋白与羟磷灰石的结合,促进釉质晶体的生长和矿化。如果其基因突变或缺失,将导致釉质发生不全。本文就KLK4的结构、KLK4的表达与生物学功能、 KLK4的调控因子、 KLK4与釉质发生不全等研究进展作一综述。%  Kallikrein 4(KLK4) is a protease expressed during the transition and maturation stages of dental enamel formation. KLK4 can degrade enamel proteins, reduce enamel proteins combination to hydroxyapatite, and promote the enamel crystals growth and mineralization. KLK4 mutations or defects cause hypomaturation amelogenesis im-perfecta. This article reviewed the structure, expression, functions, regulatory factors of KLK4 and its effect on amelogenesis imperfecta.

  14. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI Attenuates Elastase-Induced Emphysema in Mice

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    Bruno Tadeu Martins-Olivera

    2016-01-01

    Full Text Available Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD. However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group or saline (SAL group and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups. At day 28, the following analyses were performed: (I lung mechanics, (II exhaled nitric oxide (ENO, (III bronchoalveolar lavage fluid (BALF, and (IV lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

  15. Kallikrein transduced mesenchymal stem cells protect against anti-GBM disease and lupus nephritis by ameliorating inflammation and oxidative stress.

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    Yajuan Li

    Full Text Available Previously we have shown that kallikreins (klks play a renoprotective role in nephrotoxic serum induced nephritis. In this study, we have used mesenchymal stem cells (MSCs as vehicles to deliver klks into the injured kidneys and have measured their therapeutic effect on experimental antibody induced nephritis and lupus nephritis. Human KLK-1 (hKLK1 gene was transduced into murine MSCs using a retroviral vector to generate a stable cell line, hKLK1-MSC, expressing high levels of hKLK1. 129/svj mice subjected to anti-GBM induced nephritis were transplanted with 10(6 hKLK1-MSCs and hKLK1 expression was confirmed in the kidneys. Compared with vector-MSCs injected mice, the hKLK1-MSCs treated mice showed significantly reduced proteinuria, blood urea nitrogen (BUN and ameliorated renal pathology. Using the same strategy, we treated lupus-prone B6.Sle1.Sle3 bicongenic mice with hKLK1-MSCs and demonstrated that hKLK1-MSCs delivery also attenuated lupus nephritis. Mechanistically, hKLK1-MSCs reduced macrophage and T-lymphocyte infiltration into the kidney by suppressing the expression of inflammation cytokines. Moreover, hKLK1 transduced MSCs were more resistant to oxidative stress-induced apoptosis. These findings advance genetically modified MSCs as potential gene delivery tools for targeting therapeutic agents to the kidneys in order to modulate inflammation and oxidative stress in lupus nephritis.

  16. Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside view of their role and clinical significance.

    Science.gov (United States)

    Linardoutsos, Dimitrios; Gazouli, Maria; Machairas, Anastasios; Bramis, Ioannis; Zografos, Georgios C

    2014-01-01

    Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a family of 15 homologous serine proteases, participating in numerous processes of normal physiology. Considering the irreversible impact of proteases on substrates, the tissue-dependent regulation of KLKs activity becomes crucial for their beneficial role in normal homeostasis. Moreover, KLKs expression is strongly regulated at the transcriptional and post-transcriptional level by steroid hormones and miRNAs, respectively. Deregulation of KLKs expression, secretion and/or activation has been observed in most human malignancies and there is a trend to identify their role in the multi-complex process of cancer development. The identification of extracellular matrix (ECM) proteins, cell-surface receptors, cell-surface adhesion molecules and growth factors among substrates, clearly support the driving role of KLK abnormal expression and function during tumorigenesis and cancer progression. KLKs have also clinical utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer. In this review, we tried to summarize the existing literature about the role of KLKs in gastrointestinal cancers as well as to emphasize their clinical significance for patients' prognosis.

  17. Tissue kallikrein reverses insulin resistance and attenuates nephropathy in diabetic rats by activation of phosphatidylinositol 3-kinase/protein kinase B and adenosine 5'-monophosphate-activated protein kinase signaling pathways.

    Science.gov (United States)

    Yuan, Gang; Deng, Juanjuan; Wang, Tao; Zhao, Chunxia; Xu, Xizheng; Wang, Peihua; Voltz, James W; Edin, Matthew L; Xiao, Xiao; Chao, Lee; Chao, Julie; Zhang, Xin A; Zeldin, Darryl C; Wang, Dao Wen

    2007-05-01

    We previously reported that iv delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. In the current study, we evaluated the potential of a recombinant adeno-associated viral vector expressing the HK cDNA (rAAV-HK) as a sole, long-term therapy to correct insulin resistance and prevent renal damage in streptozotocin-induced type-2 diabetic rats. Administration of streptozotocin in conjunction with a high-fat diet induced systemic hypertension, diabetes, and renal damage in rats. Delivery of rAAV-HK resulted in a long-term reduction in blood pressure, and fasting plasma insulin was significantly lower in the rAAV-HK group than in the control group. The expression of phosphatidylinositol 3-kinase p110 catalytic subunit and the levels of phosphorylation at residue Thr-308 of Akt, insulin receptor B, and AMP-activated protein kinases were significantly decreased in organs from diabetic animals. These changes were significantly attenuated after rAAV-mediated HK gene therapy. Moreover, rAAV-HK significantly decreased urinary microalbumin excretion, improved creatinine clearance, and increased urinary osmolarity. HK gene therapy also attenuated diabetic renal damage as assessed by histology. Together, these findings demonstrate that rAAV-HK delivery can efficiently attenuate hypertension, insulin resistance, and diabetic nephropathy in streptozotocin-induced diabetic rats.

  18. Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation

    Science.gov (United States)

    Oliveira, Victoria Regina da Silva; Toniolo, Elaine Flamia; Feliciano, Regiane dos Santos; da Silva Jr., José Antonio; Zamuner, Stella Regina

    2016-01-01

    Background Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv), as well as the mechanisms involved was investigated. Methodology/Principal Findings Bmv (1 μg) was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT) was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT. Conclusion/Significance These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites. PMID:27749899

  19. The renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure is not dependent on enhanced kinin activity.

    Science.gov (United States)

    Nabokov, A; Amann, K; Gassmann, P; Schwarz, U; Orth, S R; Ritz, E

    1998-01-01

    Angiotensin-converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of glomerulosclerosis both in experimental models of uraemia and in patients with renal failure. It has not been documented, however, whether this is due to a decrease in angiotensin II generation or is a consequence of elevated local level of bradykinin. Morphometric investigation of renal tissue was performed in 5/6 nephrectomized (SNx) rats, i.e. untreated or treated with the ACE inhibitor ramipril (SNx-RAM), the B2 kinin receptor antagonist HOE 140 (SNx-HOE), or a combination of both (SNx-RAM + HOE) over 8 weeks. A further group of SNx received delayed treatment with ramipril from week 5 onward (SNx-RAMD). In addition, a sham-operated (SHAM) control group was studied. Systolic blood pressure was significantly lower in both SNx-RAM and SNx-RAM + HOE groups compared to (untreated) SNx. The glomerulosclerosis index (GSI) was substantially higher in the (untreated) SNx group (0.24 +/- 0.04) vs SHAM (0.02 +/- 0.01). A significantly higher GSI was found in the SNx-HOE group (0.45 +/- 0.08) as compared to (untreated) SNx. However, in the SNx-RAM, SNx-RAM + HOE, and SNx-RAMD groups, the GSI was lowered to a similar extent (0.1 +/- 0.02, 0.09 +/- 0.02, and 0.07 +/- 0.01 respectively). In addition, a concomitant attenuation of tubulointerstitial damage was noted in all the above groups. Increased kinin activity does not appear to play a major role in the renoprotective effect of ACE inhibitors in the remnant kidney model.

  20. Complement C1 esterase inhibitor levels linked to infections and contaminated heparin-associated adverse events.

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    Zhao-Hua Zhou

    Full Text Available Activation of kinin-kallikrein and complement pathways by oversulfated-chondroitin-sulfate (OSCS has been linked with recent heparin-associated adverse clinical events. Given the fact that the majority of patients who received contaminated heparin did not experience an adverse event, it is of particular importance to determine the circumstances that increase the risk of a clinical reaction. In this study, we demonstrated by both the addition and affinity depletion of C1inh from normal human plasma, that the level of C1inh in the plasma has a great impact on the OSCS-induced kallikrein activity and its kinetics. OSCS-induced kallikrein activity was dramatically increased after C1inh was depleted, while the addition of C1inh completely attenuated kallikrein activity. In addition, actual clinical infection can lead to increased C1inh levels. Plasma from patients with sepsis had higher average levels of functional C1inh and decreased OSCS-induced kallikrein activity. Lastly, descriptive data on adverse event reports suggest cases likely to be associated with contaminated heparin are inversely correlated with infection. Our data suggest that low C1inh levels can be a risk factor and high levels can be protective. The identification of risk factors for contact system-mediated adverse events may allow for patient screening and clinical development of prophylaxis and treatments.

  1. Modulation of the proteolytic cascade systems by high dose corticosteroids.

    Science.gov (United States)

    Aasen, A O; Ruud, T E; Pillgram-Larsen, J; Röise, O; Stadaas, J

    1985-01-01

    The effects of high-dose corticosteroids (HDC) on activities within the proteolytic cascade systems were studied in vitro and in vivo using chromogenic peptide substrate assays. In in vitro experiments 20 mg methylprednisolone sodium succinate (Solu-Medrol) per ml plasma significantly inhibited activation of plasma prekallikrein, prothrombin and plasminogen and reduced functional plasma kallikrein inhibition, antithrombin and antiplasmin activities. The effects of HDC on activities within these proteolytic cascade systems were further evaluated in experimental acute pancreatitis in pigs. Acute pancreatitis was induced by injection of Na-taurocholate into the pancreatic duct. Seven test animals received methylprednisolone sodium succinate 30 mg per kg intravenously for 30 minutes before the induction of pancreatitis as pretreatment. Eight animals remained untreated. Trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and mean arterial pressure (MAP) were monitored regularly before and during a 6 hour observation period. During untreated pancreatitis a reduction of PKK levels of about 40% were found, paralleled by an increased KK activity and a reduction of KKI capacity. Several of the animals experienced high TRY activities. The mortality rate was 63% (5 out of 8 animals). In the pretreated groups, all animals survived the observation period. CO and MAP were significantly less reduced than the untreated group at 6 hours. HDC was also found to reduce significantly plasma kallikrein activities in the peritoneal exudate compared with untreated animals. No changes in TRY activities were found in pretreated animals. Furthermore, plasma prekallikrein and functional plasma kallikrein inhibition values in the exudate were elevated significantly in HDC treated animals compared with untreated animals.

  2. Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent [Nα-Bodipy]-des-Arg9-bradykinin

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    Gaudreau Pierrette

    2009-03-01

    Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines, bacterial endotoxins and hyperglycaemia-induced oxidative stress. In animal models of diabetes, it contributes to pain polyneuropathy. This study aims at defining the cellular localization of B1R in thoracic spinal cord of type 1 diabetic rats by confocal microscopy with the use of a fluorescent agonist, [Nα-Bodipy]-des-Arg9-BK (BdABK and selective antibodies. Methods Diabetes was induced by streptozotocin (STZ; 65 mg/kg, i.p.. Four days post-STZ treatment, B1R expression was confirmed by quantitative real-time PCR and autoradiography. The B1R selectivity of BdABK was determined by assessing its ability to displace B1R [125I]-HPP-desArg10-Hoe140 and B2R [125I]-HPP-Hoe 140 radioligands. The in vivo activity of BdABK was also evaluated on thermal hyperalgesia. Results B1R was increased by 18-fold (mRNA and 2.7-fold (binding sites in the thoracic spinal cord of STZ-treated rats when compared to control. BdABK failed to displace the B2R radioligand but displaced the B1R radioligand (IC50 = 5.3 nM. In comparison, IC50 values of B1R selective antagonist R-715 and B1R agonist des-Arg9-BK were 4.3 nM and 19 nM, respectively. Intraperitoneal BdABK and des-Arg9-BK elicited dose-dependent thermal hyperalgesia in STZ-treated rats but not in control rats. The B1R fluorescent agonist was co-localized with immunomarkers of microglia, astrocytes and sensory C fibers in the spinal cord of STZ-treated rats. Conclusion The induction and up-regulation of B1R in glial and sensory cells of the spinal cord in STZ-diabetic rats reinforce the idea that kinin B1R is an important target for drug development in pain processes.

  3. Comparison of gene expression of mitogenic kinin path in adherent and non-adherent CD 34-stem cells using oligonucleotide microarrays.

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    Krzysztof Machaj

    2008-02-01

    Full Text Available One of the more interesting cells present in the umbilical cord blood - as far as their potential clinical use is concerned - are stem cells not presenting the CD34 antigen. These are the pluripotential cells with their biological properties similar to mesenchymal stem cells, with the ability to differentiate into such tissue types as bone, cartilage, nervous (to some extent, glia and muscle. The authors compared the activity of genes coding the proteins in mitogenic signal paths activated by kinin receptors using oligonucleotide microarrays in adherent and non-adherent CD 34- cells derived from umbilical cord blood. In the linear regression model with a 95% prognosis area for differentiating genes outside this area, the following genes were selected: c-jun (present in 3 isoforms and c-fos. The fos and jun genes create the AP-1 transcriptive factor which regulates the expression of genes taking part in numerous cellular processes, including the cell cycle and mitosis. The obtained results shed some light on the molecular processes behind the MSC proliferation and are a starting point for further studies on the mesenchymal stem cell biology.

  4. Recombinant adeno-associated virus-mediated human kallikrein gene therapy prevents high-salt diet-induced hypertension without effect on basal blood pressure

    Institute of Scientific and Technical Information of China (English)

    Jiang-tao YAN; Tao WANG; Juan LI; Xiao XIAO; Dao-wen WANG

    2008-01-01

    Aim: To investigate the effects of the expression of human kallikrein (HK) on basal level blood pressure and high-salt diet-induced hypertension. Methods: We delivered the recombinant adeno-associated viral (rAAV)-mediated HK (rAAV-HK) gene and rAAV-LacZ (as the control) to normal, adult Sprague-Dawley rats. The animals were administered a normal diet in the first 4 weeks, followed by a high-salt diet. The expression of HK in the rats was assessed by ELISA and RT-PCR. Blood pressure and Na~ and K~ urinary excretion were monitored. Results: Under the normal diet, no obvious changes in blood pressure and Na+ and K+ urinary excretion were observed. When the high-salt diet was administered, sys-tolic blood pressure in the control animals receiving rAAV-LacZ increased from 122.3±1. 13 mmHg to a stable 142.4±1.77 mmHg 8 weeks after the high-salt diet. In contrast, there was no significant increase in the blood pressure in the rAAV-HK-treated group, in which the blood pressure remained at 121.9±1.73 mmHg. In the rAAV-HK-treated group, Na+ and K+ urinary excretion were higher compared to those of the control group. The morphological analysis showed that HK delivery remarkably protected against renal damage induced by a high-salt intake. Conclusion: Our study indicates that rAAV-mediated human tissue kallikrein gene delivery is a potentially safe method for the long-term treatment of hypertension. More importantly, it could be applied in the salt-sensitive population to prevent the occurrence of hypertension.

  5. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat

    OpenAIRE

    Mehrangiz Khanmoradi; Seyyed Ali Mard; Nahid Aboutaleb; Malihe Nobakht; Masoud Mahmoudian

    2014-01-01

    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion inj...

  6. Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14.

    Science.gov (United States)

    de Veer, Simon J; Swedberg, Joakim E; Parker, Edward A; Harris, Jonathan M

    2012-04-01

    An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.

  7. Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor.

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    Ulf Meyer-Hoffert

    Full Text Available Kallikreins-related peptidases (KLKs are serine proteases and have been implicated in the desquamation process of the skin. Their activity is tightly controlled by epidermal protease inhibitors like the lympho-epithelial Kazal-type inhibitor (LEKTI. Defects of the LEKTI-encoding gene serine protease inhibitor Kazal type (Spink5 lead to the absence of LEKTI and result in the genodermatose Netherton syndrome, which mimics the common skin disease atopic dermatitis. Since many KLKs are expressed in human skin with KLK5 being considered as one of the most important KLKs in skin desquamation, we proposed that more inhibitors are present in human skin. Herein, we purified from human stratum corneum by HPLC techniques a new KLK5-inhibiting peptide encoded by a member of the Spink family, designated as Spink9 located on chromosome 5p33.1. This peptide is highly homologous to LEKTI and was termed LEKTI-2. Recombinant LEKTI-2 inhibited KLK5 but not KLK7, 14 or other serine proteases tested including trypsin, plasmin and thrombin. Spink9 mRNA expression was detected in human skin samples and in cultured keratinocytes. LEKTI-2 immune-expression was focally localized at the stratum granulosum and stratum corneum at palmar and plantar sites in close localization to KLK5. At sites of plantar hyperkeratosis, LEKTI-2 expression was increased. We suggest that LEKTI-2 contributes to the regulation of the desquamation process in human skin by specifically inhibiting KLK5.

  8. Tissue kallikrein induces SH-SY5Y cell proliferation via epidermal growth factor receptor and extracellular signal-regulated kinase1/2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Zhengyu [Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040 (China); Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437 (China); Yang, Qi; Cui, Mei; Liu, Yanping [Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040 (China); Wang, Tao; Zhao, Hong [Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437 (China); Dong, Qiang, E-mail: qiang_dong163@163.com [Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040 (China)

    2014-03-28

    Highlights: • TK promotes EGFR phosphorylation in SH-SY5Y cells. • TK activates ERK1/2 and p38 phosphorylation in SH-SY5Y cells. • TK mediates SH-SY5Y cell proliferation via EGFR and ERK1/2 pathway. - Abstract: Tissue kallikrein (TK) is well known to take most of its biological functions through bradykinin receptors. In the present study, we found a novel signaling pathway mediated by TK through epidermal growth factor receptor (EGFR) in human SH-SY5Y cells. We discovered that TK facilitated the activation of EGFR, extracellular signal-regulated kinase (ERK) 1/2 and p38 cascade. Interestingly, not p38 but ERK1/2 phosphorylation was severely compromised in cells depleted of EGFR. Nevertheless, impairment of signaling of ERK1/2 seemed not to be restricted to EGFR phosphorylation. We also observed that TK stimulation could induce SH-SY5Y cell proliferation, which was reduced by EGFR down-regulation or ERK1/2 inhibitor. Overall, our findings provided convincing evidence that TK could mediate cell proliferation via EGFR and ERK1/2 pathway in vitro.

  9. 组织激肽释放酶家族在胰腺癌中的研究进展%Kallikrein-related peptidases in pancreatic cancer: expression and significance

    Institute of Scientific and Technical Information of China (English)

    郑苏丽; 熊光冰; 曹喆; 杨刚; 张太平

    2016-01-01

    Pancreatic cancer is a one of the most malignant digestive cancer.Because the lack of effective methods for early diagnosis,most patients have been ineligible for surgical resection when diagnosed.Kallikrein family is a group of serine proteases,because of its ability to decompose the extracellular matrix proteins,it may be closely related to the invasion and metastasis of various cancers.And some members of kallikrein family may become cancer diagnostic biomarkers.This paper reviews all the recent articles about kallikrein family study in pancreatic cancer.%胰腺癌是一种恶性程度极高的消化道恶性肿瘤.因其缺乏有效的早期诊断方法,多数患者确诊时已无法进行根治性手术.激肽释放酶家族是一组丝氨酸蛋白酶,因其具有分解细胞外基质蛋白的能力,可能与多种癌症的侵袭和转移密切相关,并有可能成为多种癌症诊断的生物标志物.本文回顾了近年来激肽释放酶基因家族研究中与胰腺癌有关的文章,对激肽释放酶家族成员在胰腺癌中的表达及意义进行综述.

  10. The kallikrein-related peptidase 13 (KLK13) gene is substantially up-regulated after exposure of gastric cancer cells to antineoplastic agents.

    Science.gov (United States)

    Florou, Dimitra; Mavridis, Konstantinos; Scorilas, Andreas

    2012-12-01

    Gastric cancer constitutes one of the most common neoplasms globally. Kallikrein-related peptidases have attracted interest as potential tumor markers and future targets for novel cancer therapeutics. We have recently reported KLK13 clinical importance as a favorable prognostic biomarker for gastric cancer patients' survival. By aiming to explore how the molecular profile of KLK13 is modified in stomach cancer cells treated with antineoplastic drugs, we examined, for the first time, the mRNA alterations of this gene following gastric cancer cells' exposure to the prominent chemotherapeutic substances epirubicin, oxaliplatin, or methotrexate. The antiproliferative effects of these agents, on AGS cells' growth, were determined by the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide and trypan blue assays. Total RNA, isolated from the harvested cells, was reverse-transcribed to cDNA. KLK13 levels were quantified via real-time PCR using the SYBR Green chemistry. The relative changes of KLK13 expression were calculated with the comparative C (t) (2(-ddCt)) method. Distinct KLK13 profiles resulted from AGS cells' incubation with epirubicin or methotrexate for 24, 36, and 48 h. KLK13 expression increased in a time-dependent manner up to 5.70 times (for epirubicin) or 5.76 times (for methotrexate) at 48 h compared with the corresponding untreated cells. According to our results, KLK13 expression is implicated in the molecular pathways that are triggered after administration of anticancer agents on gastric cancer cells. Moreover, our data support the possibility that KLK13 may be exploited as a future molecular predictor of gastric cancer cells' response to chemotherapy.

  11. Association of Polymorphism rs198977 in Human Kallikrein-2 Gene (KLK2 with Susceptibility of Prostate Cancer: A Meta-Analysis.

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    Lishan Wang

    Full Text Available To assess the association of polymorphism rs198977 in the human kallikrein-2 gene (KLK2 and risk of prostate cancer (PCa.Two investigators independently searched the PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library and Chinese National Knowledge Infrastructure (CNKI. Pooled odds ratios (ORs and 95% confidence intervals (95% CIs for rs198977 and PCa were calculated in a fixed-effects model (the Mantel-Haenszel method and a random-effects model (the DerSimonian and Laird method when appropriate.Six studies met the inclusion criteria in this meta-analysis, which included 5859 PCa cases and 4867 controls. Overall, rs198977 was associated with the PCa risk (TT+CT vs. CC, pooled OR = 1.163, 95% CI = 1.076-1.258, P-value <0.0001. When stratified by ethnicity, significant association was observed in Caucasian samples under both allele comparison (T vs. C, pooled OR = 1.152, 95% CI = 1.079-1.229, P-value <0.0001 and dominant model (TT+CT vs. CC, pooled OR = 1.197, 95% CI = 1.104-1.297, P-value <0.0001. In the overall analysis, a comparably significant increase in the frequency of allele T for rs198977 was detected between cases and controls in Caucasian.This meta-analysis suggests that rs198977 of KLK2 was associated with susceptibility of PCa in Caucasian and the allele T might increase the risk of PCa in Caucasian.

  12. Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvβ3 expression.

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    Shen Shen Fu

    Full Text Available BACKGROUND: Human tissue kallikrein (hTK plays an essential role in the physiological and pathological mechanisms of blood vessels. This study aimed to determine whether angiogenesis induced by endothelial progenitor cells (EPCs transduced with the adenovirus-mediated hTK gene could improve blood flow in rat hindlimb ischemia in vivo and to establish a promising mechanism in vitro. METHODS: EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK-transduced EPCs or Ad/GFP-transduced EPCs were administered to Wister rats with hindlimb ischemia through therapeutic neovascularization. Muscular capillary density (MCD, blood flow (BF, and the number of myofibers were measured at days 7, 14, and 21 after treatment. Expressions of integrin αvβ3 and endothelial nitric oxide synthase (eNOS were detected on the surface of EPCs. RESULTS: MCD, BF, and the number of myofibers in rats with Ad/hTK-transduced EPCs remarkably increased at day 21 after treatment compared with rats with Ad/GFP-transduced EPCs or the control group (P<0.01. Expressions of integrin αvβ3 and eNOS protein on the surface of EPCs also increased in rats with Ad/hTK-transduced EPCs. The levels of integrin αvβ3 expression were reduced by PI3K and eNOS blockade, and the inhibitor of integrin αvβ3 abrogated the migration and adhesion of hTK-transduced EPCs (P<0.05. CONCLUSION: hTK gene delivery in vivo improves the natural angiogenic response to ischemia. The ability of hTK gene-transduced EPCs can be enhanced in vitro, in which integrin αvβ3 plays a role in the process.

  13. Micro-RNA analysis of renal biopsies in human lupus nephritis demonstrates up-regulated miR-422a driving reduction of kallikrein-related peptidase 4.

    Science.gov (United States)

    Krasoudaki, Eleni; Banos, Aggelos; Stagakis, Elias; Loupasakis, Konstantinos; Drakos, Elias; Sinatkas, Vaios; Zampoulaki, Amalia; Papagianni, Aikaterini; Iliopoulos, Dimitrios; Boumpas, Dimitrios T; Bertsias, George K

    2016-10-01

    Aberrancies in gene expression in immune effector cells and in end-organs are implicated in lupus pathogenesis. To gain insights into the mechanisms of tissue injury, we profiled the expression of micro-RNAs in inflammatory kidney lesions of human lupus nephritis (LN). Kidney specimens were from patients with active proliferative, membranous or mixed LN and unaffected control tissue. Micro-RNAs were quantified by TaqMan Low Density Arrays. Bioinformatics was employed to predict gene targets, gene networks and perturbed signaling pathways. Results were validated by transfection studies (luciferase assay, real-time PCR) and in murine LN. Protein expression was determined by immunoblotting and immunohistochemistry. Twenty-four micro-RNAs were dysregulated (9 up-regulated, 15 down-regulated) in human LN compared with control renal tissue. Their predicted gene targets participated in pathways associated with TGF-β, kinases, NF-κB, HNF4A, Wnt/β-catenin, STAT3 and IL-4. miR-422a showed the highest upregulation (17-fold) in active LN and correlated with fibrinoid necrosis lesions (β = 0.63, P = 0.002). In transfection studies, miR-422a was found to directly target kallikrein-related peptidase 4 (KLK4) mRNA. Concordantly, KLK4 mRNA was significantly reduced in the kidneys of human and murine LN and correlated inversely with miR-422a levels. Immunohistochemistry confirmed reduced KLK4 protein expression in renal mesangial and tubular epithelial cells in human and murine LN. KLK4, a serine esterase with putative renoprotective properties, is down-regulated by miR-422a in LN kidney suggesting that, in addition to immune activation, local factors may be implicated in the disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  14. Involvement of DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP Pathways in Human Tissue Kallikrein 1 Protecting Erectile Function in Aged Rats

    Science.gov (United States)

    Tang, Zhe; Rao, Ke; Wang, Tao; Chen, Zhong; Wang, Shaogang; Liu, Jihong; Wang, Daowen

    2017-01-01

    Our previous studies had reported that Human Tissue Kallikrein 1 (hKLK1) preserved erectile function in aged transgenic rats, while the detailed mechanism of hKLK1 protecting erectile function in aged rats through activation of cGMP and cAMP was not mentioned. To explore the latent mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 18 months old and divided into four groups: young WTR (yWTR) as the control, aged WTR (aWTR), aged TGR (aTGR) and aged TGRs with HOE140 (aTGRH). Erectile function of all rats was evaluated by cavernous nerve electrostimulation method and measured by the ratio of intracavernous pressure/ mean arterial pressure (ICP/MAP) in rats. Expression levels of cAMP and cGMP were assessed, and related signaling pathways were detected by western blot, immunohistochemistry and RT-PCR. Our experiment results showed erectile function of the aWTR group and aTGRH group was lower compared with those of other two groups. Also, expression levels of cAMP and cGMP were significantly lower than those of other two groups. Moreover, expressions of related signaling pathways including DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP were also downregulated in the corpus cavernosum of rats in aWTR group. Our finding revealed hKLK1 played a protective role in age-related ED. The DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP pathways that were linked to the mechanism hKLK1 could increase the levels of cGMP and cAMP, which might provide novel therapy targets for age-related ED. PMID:28103290

  15. Spatio-temporal expression of MMP-2, MMP-9 and tissue kallikrein in uteroplacental units of the pregnant guinea-pig (Cavia porcellus

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    Rey Sergio

    2007-07-01

    Full Text Available Abstract Background In humans trophoblast invasion and vascular remodeling are critical to determine the fate of pregnancy. Since guinea-pigs share with women an extensive migration of the trophoblasts through the decidua and uterine arteries, and a haemomonochorial placenta, this species was used to evaluate the spatio-temporal expression of three enzymes that have been associated to trophoblast invasion, MMP-2, MMP-9 and tissue kallikrein (K1. Methods Uteroplacental units were collected from early to term pregnancy. MMP-2, MMP-9 and K1 were analysed by immunohistochemistry and Western blot. The activities of MMP-2 and MMP-9 were assessed by gelatin zymography. Results Immunoreactive MMP-2, MMP-9 and K1 were detected in the subplacenta, interlobar and labyrinthine placenta, syncytial sprouts and syncytial streamers throughout pregnancy. In late pregnancy, perivascular or intramural trophoblasts expressed the three enzymes. The intensity of the signal in syncytial streamers was increased in mid and late pregnancy for MMP-2, decreased in late pregnancy for MMP-9, and remained stable for K1. Western blots of placental homogenates at days 20, 40 and 60 of pregnancy identified bands with the molecular weights of MMP-2, MMP-9 and K1. MMP-2 expression remained constant throughout gestation. In contrast, MMP-9 and K1 attained their highest expression during midgestation. Placental homogenates of 20, 40 and 60 days yielded bands of gelatinase activity that were compatible with MMP-2 and MMP-9 activities. ProMMP-2 and MMP-9 activities did not vary along pregnancy, while MMP-2 and MMP-9 increased at 40 and 40–60 days respectively. Conclusion The spatio-temporal expression of MMPs and K1 supports a relevant role of these proteins in trophoblast invasion, vascular remodeling and placental angiogenesis, and suggests a functional association between K1 and MMP-9 activation.

  16. Amelioration of cardiac function and activation of anti-inflammatory vasoactive peptides expression in the rat myocardium by low level laser therapy.

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    Martha Trindade Manchini

    Full Text Available Low-level laser therapy (LLLT has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI. However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS and Kallikrein-Kinin System (KKS vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO generation.

  17. Interference of kallikrein 1b26 (klk1b26 translation by microRNA specifically expressed in female mouse submandibular glands: an additional mechanism for sexual dimorphism of klk1b26 protein in the glands

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    Kurihara Kinji

    2011-11-01

    Full Text Available Abstract Background Mouse kallikrein 1b26 (klk1b26 protein is more abundant in male submandibular glands (SMGs than in female ones. This sexual dimorphism has been thought to be due to increased mRNA synthesis stimulated by androgen. However, the klk1b26 protein level in female SMG is far less than that expected from the mRNA level, suggesting an additional mechanism for down-regulation of klk1b26 expression in female SMGs. Methods We examined the effects of small non-coding RNAs in mouse SMGs on in vitro translation of klk1b26 using a reticulocyte lysate system and reverse transcription (RT-PCR for klk1b26 mRNA. Statistical analyses were performed with a computer package (Microsoft Excel. Results The microRNA (miRNA preparation from female SMGs, but not male SMGs, interfered with the in vitro translation of the klk1b26 protein and inhibited the RT-PCR for klk1b26 mRNA with forward primers targeting its 5'-terminal region (between the 15th and 40th nucleotide from the 5'-terminal. The miRNA preparation from castrated mouse SMGs showed the inhibitory effect on the klk1b26 translation, but that from a 5α-dihydrotestosterone-treated female mouse SMGs did not. Synthetic miRNAs (miR-325 and miR-1497a, which have partial complementarity with klk1b26 mRNA at its 5'-terminal region (15th to 40th nucleotide position from the 5'-terminal, also interfered with the in vitro klk1b26 translation. When the female miRNA preparation was incubated with a 30-nucleotide-long single-strand oligoDNA (named [15th-44th]ssDNA, whose sequence corresponded to the 15th to 44th position from the 5'-terminal of klk1b26 mRNA prior to the addition into the in vitro translation system, the inhibitory effect of the miRNA preparation on klk1b26 translation disappeared, while [15th-44th]ssDNA itself had no effect on the translation. Preincubation of the miRNA preparation with another single-strand DNA ([169th-198th]ssDNA, whose sequence corresponded with 169th to 198th position

  18. Ecallantide is a novel treatment for attacks of hereditary angioedema due to C1 inhibitor deficiency

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    Farkas H

    2011-05-01

    Full Text Available Henriette Farkas, Lilian Varga3rd Department of Internal Medicine, Semmelweis University, Budapest, HungaryAbstract: Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor protein is a rare disease, characterized by paroxysms of edema formation in the subcutis and in the submucosa. Edema can cause obstruction of the upper airway, which may lead to suffocation. Prompt elimination of edema is necessary to save patients from this life-threatening condition. Essentially, these edematous attacks are related to the activation of the kinin-kallikrein system and the consequent release of bradykinin. Ecallantide (known as DX-88 previously, a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. This is the only agent approved recently by the FDA for all localizations of edematous HAE attacks. Its advantages include no risk of viral contamination, high selectivity, very rapid onset of action, good tolerability, and straightforward subcutaneous administration. Owing to the risk of anaphylaxis, ecallantide should be administered by a health care professional. A postmarketing survey to improve risk-assessment and risk-minimization has been launched. The results of these studies may lead to the approval of ecallantide for self-administration.Keywords: hereditary angioedema, C1-inhibitor deficiency, treatment, bradykinin, kallikrein inhibitor, subcutaneous administration

  19. Periodontal hastalıklar ile erken yaşlarda görülen ateroskleroza bağlı koroner hastalıklar arasındaki ilişkinin değerlendirilmesi

    OpenAIRE

    KARAGÖZ, Şükran

    2011-01-01

    Bu çalışmada erken yaşta (?50 yaş) koroner arter hastalığı (KAH) tanısı almış olan kişilerle aterosklerotik kardiyovasküler hastalığı olmayanlar arasında bazı periodontal parametreler ve bazı kan tahlili parametreleri bakımından kıyaslama yaparak, periodontal hastalık gibi enflamatuvar bir durumun erken yaşlarda ortaya çıkışı ile erken yaşlarda KAH gelişimi arasındaki olası ilişkinin değerlendirilmesi amaçlanmıştır.Çalışmamızda KAH tanısı almış, yaşları 31-50 arasında (or...

  20. Clinical observation on effect of pancreatic kallikrein unite zinc gluconate on asthenozoospermia%胰激肽原酶联合葡萄糖酸锌片治疗弱精子症的临床研究

    Institute of Scientific and Technical Information of China (English)

    檀大羡; 谢伟; 刘琼东; 李征

    2012-01-01

    Objective To investigate the clinical efficacy of pancreatic kallikrein unite zinc gluconate tablets in treatment of asthenozoospermia. Methods Seventy asthenozoospermia cases were randomly divided into treatment group (40 cases) and control group(30 cases). The treatment group were given pancreatic kallikrein and zinc gluconate tablets and those in the control group were treated with adenosine triphosphate tablets (ATP) and vitamin £ capsules for a course of 3 months. The semen volume,sperm concentration,total activity and the percentage of progressive motility were compared before and after treatment. Results The total effective rate in treatment group and control group were 70.0% and 43.3% respectively,showing significant difference between two groups (P<0.05).There were no significant differences in semen volume and sperm concentration before and after treatment,Whereas the sperm total activity and the percentage of progressive motility before and after treatment in each group and between two groups after treatment were significantly different(P<0.05). Conclusion Pancreatic kallikrein unite zinc gluconate is effective in treatment of asthenospermia.%目的 探讨胰激肽原酶联合葡萄糖酸锌片治疗弱精子症的临床疗效.方法 将70例弱精子症患者随机分为治疗组(40例)对照组(30例).治疗组服用胰激肽原酶和葡萄糖酸锌片,对照组服用三磷酸腺苷片(ATP)和维生素E胶丸,两组治疗时间均为3个月.比较两组治疗前后精液量、精子浓度、总活力、前向运动精子百分率的变化情况.结果 治疗组总有效率为70.0%,对照组为43.3%,两组治疗后比较差异有统计学意义(P<0.05);治疗后精液量、精子浓度治疗前后差异无统计学意义(P>0.05),而总活力、前向运动精子百分率各组治疗前后及两组治疗后比较差异有统计学意义(P<0.05).结论 应用胰激肽原酶联合葡萄糖酸锌片治疗弱精子症有一定的疗效.

  1. Role of endothelial dysfunction in the pathogenesis of diabetic retinopathy in patients with type 2 diabetes

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    I. V. Vorobyeva

    2014-07-01

    Full Text Available The reason for the progressive vision reduction at diabetes mellitus (DM is diabetic retinopathy (DR. When type 2 diabetes combined with hypertension (Ht, it increases the risk of vision loss by 25 times. In the pathogenesis of DR is important to endothelial dysfunction and a variety of biochemical processes (an excess of intracellular sorbitol, non-enzymatic glycation of proteins, oxidative stress. there is a decrease in generation vasodilating factors, nitric oxide, with a simultaneous increase of endothelin, which causes vasoconstriction. Key processes underlying the development of DR, such as increased vascular permeability, edema, neovasculariza- tion, inflammation and associated with the effects of kallikrein-kinin system. In the pathogenesis of DR can be involved independent intraocular renin-angiotensin system, which is an important mediator of angiogenesis and increased vascular permeability. Damage to the endothelium of retinal vessels leads to ischemia of the retina. there is growth and development of newly formed blood vessels, which may provoke recurrent bleeding.

  2. Factor XII-Driven Inflammatory Reactions with Implications for Anaphylaxis

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    Lysann Bender

    2017-09-01

    Full Text Available Anaphylaxis is a life-threatening allergic reaction. It is triggered by the release of pro-inflammatory cytokines and mediators from mast cells and basophils in response to immunologic or non-immunologic mechanisms. Mediators that are released upon mast cell activation include the highly sulfated polysaccharide and inorganic polymer heparin and polyphosphate (polyP, respectively. Heparin and polyP supply a negative surface for factor XII (FXII activation, a serine protease that drives contact system-mediated coagulation and inflammation. Activation of the FXII substrate plasma kallikrein leads to further activation of zymogen FXII and triggers the pro-inflammatory kallikrein–kinin system that results in the release of the mediator bradykinin (BK. The severity of anaphylaxis is correlated with the intensity of contact system activation, the magnitude of mast cell activation, and BK formation. The main inhibitor of the complement system, C1 esterase inhibitor, potently interferes with FXII activity, indicating a meaningful cross-link between complement and kallikrein–kinin systems. Deficiency in a functional C1 esterase inhibitor leads to a severe swelling disorder called hereditary angioedema (HAE. The significance of FXII in these disorders highlights the importance of studying how these processes are integrated and can be therapeutically targeted. In this review, we focus on how FXII integrates with inflammation and the complement system to cause anaphylaxis and HAE as well as highlight current diagnosis and treatments of BK-related diseases.

  3. [Efficacy of magnetolaser therapy of patients with an inflammatory form of chronic abacterial prostatitis].

    Science.gov (United States)

    Kogan, M I; Shangichev, A V; Belousov, I I

    2010-01-01

    To assess efficacy of magnetolaser therapy (KAP-ELM-01 Andro-Gin unit) in the treatment of inflammatory chronic abacterial prostatitis (ICAP), 68 ICAP patients were divided into 2 groups. Group 1 patients (n = 33) received standard therapy. Group 2 patients received standard therapy plus magnetolaser (ML) therapy. The effect was assessed by the symptoms scale and indices of kallirrein-kinin system. After treatment pain relieved by 36,9%, on the average, in group 1 and by 63.1% in group 2. Lower urinary tract symptoms regressed insignificantly in both groups: by 4.8% and 7.1%, respectively. Quality of life improved by 27.6 and 65.5%, respectively. Kallikrein activity in prostatic secretion remained high in both groups. A 21.7% rise (p prostatic secretion normalized in group 2. Total activity of serin proteinases lowered in both groups (p prostatic secretion. ML therapy is more effective.

  4. Skin Barrier Function Is Not Impaired and Kallikrein 7 Gene Polymorphism Is Frequently Observed in Korean X-linked Ichthyosis Patients Diagnosed by Fluorescence in Situ Hybridization and Array Comparative Genomic Hybridization.

    Science.gov (United States)

    Lee, Noo Ri; Yoon, Na Young; Jung, Minyoung; Kim, Ji-Yun; Seo, Seong Jun; Wang, Hye-Young; Lee, Hyeyoung; Sohn, Young Bae; Choi, Eung Ho

    2016-08-01

    X-linked ichthyosis (XLI) is a recessively inherited ichthyosis. Skin barrier function of XLI patients reported in Western countries presented minimally abnormal or normal. Here, we evaluated the skin barrier properties and a skin barrier-related gene mutation in 16 Korean XLI patients who were diagnosed by fluorescence in situ hybridization and array comparative genomic hybridization analysis. Skin barrier properties were measured, cytokine expression levels in the stratum corneum (SC) were evaluated with the tape stripped specimen from skin surface, and a genetic test was done on blood. XLI patients showed significantly lower SC hydration, but normal basal trans-epidermal water loss and skin surface pH as compared to a healthy control group. Histopathology of ichthyosis epidermis showed no acanthosis, and levels of the pro-inflammatory cytokines in the corneal layer did not differ between control and lesional/non-lesional skin of XLI patients. Among the mutations in filaggrin (FLG), kallikrein 7 (KLK7), and SPINK5 genes, the prevalence of KLK7 gene mutations was significantly higher in XLI patients (50%) than in controls (0%), whereas FLG and SPINK5 prevalence was comparable. Korean XLI patients exhibited unimpaired skin barrier function and frequent association with the KLK7 gene polymorphism, which may differentiate them from Western XLI patients.

  5. Regulation of bradykinin B2-receptor expression by oestrogen

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    Madeddu, Paolo; Emanueli, Costanza; Varoni, Maria Vittoria; Demontis, Maria Piera; Anania, Vittorio; Gorioso, Nicola; Chao, Julie

    1997-01-01

    Tissue kallikrein is overexpressed in the kidney of female rats, this sexual dimorphism being associated with a greater effect of early blockade of bradykinin B2-receptors on female blood pressure phenotype. We evaluated the effect of ovariectomy and oestradiol benzoate (50 μg kg−1 every two days for two weeks) on the vasodepressor response to intra-arterial injection of bradykinin (150–900 ng kg−1) and on the expression of bradykinin B2-receptors.Ovariectomy reduced the magnitude of the vasodepressor response to bradykinin and unmasked a secondary vasopressor effect. Oestrogen replacement restored the vasodepressor response to bradykinin in ovariectomized rats.The vasodepressor responses to sodium nitroprusside (3–18 μg kg−1), acetylcholine (30–600 ng kg−1), desArg9-bradykinin (150–900 ng kg−1) or prostaglandin E2 (30–600 ng kg−1) were significantly reduced by ovariectomy. Oestrogen restored to normal the responses to desArg9-bradykinin, acetylcholine and prostaglandin E2, but not that to sodium nitroprusside.B2-receptor mRNA levels were decreased by ovariectomy in the aorta and kidney and they were restored to normal levels by oestrogen. Neither ovariectomy nor oestradiol affected receptor expression in the heart and uterus.These results indicate that oestrogen regulates B2-receptor gene expression and function. Since kinins exert a cardiovascular protective action, reduction in their vasodilator activity after menopause might contribute to the increased risk of pathological cardiovascular events. Conversely, the cardioprotective effects of oestrogen replacement might be, at least in part, mediated by activation of the kallikrein-kinin system. PMID:9283715

  6. Ecallantide is a novel treatment for attacks of hereditary angioedema due to C1 inhibitor deficiency.

    Science.gov (United States)

    Farkas, Henriette; Varga, Lilian

    2011-01-01

    Hereditary angioedema (HAE) resulting from the deficiency of the C1 inhibitor protein is a rare disease, characterized by paroxysms of edema formation in the subcutis and in the submucosa. Edema can cause obstruction of the upper airway, which may lead to suffocation. Prompt elimination of edema is necessary to save patients from this life-threatening condition. Essentially, these edematous attacks are related to the activation of the kinin-kallikrein system and the consequent release of bradykinin. Ecallantide (known as DX-88 previously), a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. This is the only agent approved recently by the FDA for all localizations of edematous HAE attacks. Its advantages include no risk of viral contamination, high selectivity, very rapid onset of action, good tolerability, and straightforward subcutaneous administration. Owing to the risk of anaphylaxis, ecallantide should be administered by a health care professional. A postmarketing survey to improve risk-assessment and risk-minimization has been launched. The results of these studies may lead to the approval of ecallantide for self-administration.

  7. Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive.

    Directory of Open Access Journals (Sweden)

    Antoine eHuart

    2015-02-01

    Full Text Available Background: Renal tubulointerstitial fibrosis is the pathological hallmark of chronic kidney disease. Currently, inhibitors of the renin angiotensin system (RAS remain the sole therapy in human displaying antifibrotic properties. Further antifibrotic molecules are needed. We have recently reported that the delayed blockade of the bradykinin B1 receptor (B1R reduced the development of fibrosis in two animal models of renal fibrosis. The usefulness of new drugs also resides in outperforming the gold standards and eventually being additive or complementary to existing therapies. Methods: In this study we compared the efficacy of a B1R antagonist (B1Ra with that of an angiotensin type 1 receptor antagonist (AT1a in the unilateral ureteral obstruction (UUO model of renal fibrosis and determined whether bi-therapy presented higher efficacy than any of the drugs alone. Results: B1R antagonism was as efficient as the gold-standard AT1a treatment. However bitherapy did not improve the antifibrotic effects at the protein level. We sought for the reason of the absence of this additive effect by studying the expression of a panel of genes involved in the fibrotic process. Interestingly, at the molecular level the different drugs targeted different players of fibrosis that, however, in this severe model did not result in improved reduction of fibrosis at the protein level. Conclusions: As the B1R is induced specifically in the diseased organ and thus potentially displays low side effects it might be an interesting alternative in cases of poor tolerability to RAS inhibitors.

  8. Ateroskleroz ile il-1α (interleukin-1α -889 c/t gen polimorfizmi arasındaki ilişkinin araştırılması

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    Hasan Başçil

    2014-06-01

    Full Text Available Amaç. Genetik ve çevresel faktörler arasındaki ilişki sonucu ortaya çıkan kardiyovasküler hastalıkların gelişiminde inflamasyon anahtar rol oynamaktadır. İnterlökin-1α (IL-1α nın proinflamasyon regülasyonunda önemli rolü vardır. Bu çalışmada IL-1α-889 C/T polimorfizmi ile ateroskleroz arasındaki ilişkinin araştırılması amaçlanmıştır. Yöntem. Bu çalışma popülasyonu 117 hasta (Grup I ve 117 sağlıklı (Grup II bireyden oluşmuştur. Grup I ve Grup II deki bireylerin genomik DNA’sı izole edildi. IL-1α genotipleri rastgele seçilen örneklerden direkt dizi analizi yapılarak doğrulandı. Bulgular. Grup I 78 erkek ve 39 kadın bireyden, Grup II ise 49 erkek ve 68 kadın bireyden oluşmaktadır. Grup I bireylerin yaş ortalaması 61,06; Grup II bireylerin yaş ortalaması ise 59,47’dir. Grup I’de 43 bireyde, Grup II’de ise 28 bireyde yüksek kolesterol (total kolesterol>200 mg/dL bulundu. Grup I’de 62 bireyde, Grup II’de 51 bireyde sigara içiciliği bulundu. Grup I’de 81 bireyde yüksek tansiyon ( sistolik kan basıncı>140 mmHg ve/veya diyastolik kan basıncı >90 mmHg, 42 bireyde diyabet, Grup II’de 32 bireyde yüksek tansiyon, 41 bireyde diyabet bulundu. Aterosklerotik Grup I’de CC genotip taşıyan bireyler grubun %54,70’ini, CT genotip taşıyan bireyler %35,04’nü ve TT genotip taşıyan bireyler ise %10,25’ini oluşturmaktadır. Grup II’de ise bu oranlar CC genotip taşıyanlarda %59,82; CT genotip taşıyanlarda %30,76 ve TT genotip taşıyanlarda %9,40 olarak saptanmıştır. IL-1α polimorfizmi için C allel frekansı Grup II’de %75,21 ve Grup I’de %72,22’dir. T allel frekansı dağılımı Grup II’de %24,78 ve Grup I’de ise %27,77’dir. Sonuç. Koroner Arter hastalığı olan Grup I ile, kontrol grubu olan Grup II arasında yaş, cinsiyet dağılımı, hipertansiyon ve hiperkolesterolemi açısından istatistiksel olarak anlamlı bir ilişki saptanm

  9. Ders çalışma becerileri ile akademik risk alma arasındaki ilişkinin kanonik korelasyon ile incelenmesi [An investigation of the relationship between study skills and academic risk taking with canonical correlation

    Directory of Open Access Journals (Sweden)

    Mustafa İLHAN

    2013-10-01

    Full Text Available Bu araştırmada ders çalışma becerileri ile akademik risk alma arasındaki ilişkinin incelenmesi amaçlanmıştır. Bu amaca uygun olarak araştırmada ilişkisel tarama modeli kullanılmıştır. Araştırmanın çalışma grubunu, 2011-2012 Öğretim Yılı Güz Dönemi’nde Siirt Üniversitesi Eğitim Fakültesi’nde öğrenim gören 221 üniversite öğrencisi oluşturmaktadır. Araştırmada öğrencilerin ders çalışma becerilerini ölçmek için Bay, Tuğluk ve Gençdoğan (2004 tarafından geliştirilen “Ders Çalışma Becerileri Ölçeği” kullanılmıştır. Öğrencilerin akademik risk alma davranışlarını ölçmek amacıyla ise Clifford (1991 tarafından geliştirilen ve Korkmaz (2002 tarafından Türkçe’ye uyarlanan “Akademik Risk Alma Ölçeği” kullanılmıştır. Araştırmada motivasyon, zaman yönetimi ve sınava hazırlanma-sınav kaygısı yönetimi değişkenlerinden oluşan ders çalışma becerileri veri seti ile başarısızlık sonrası olumsuzluk eğilimi, güç işlemleri tercih etme eğilimi, başarısızlık sonrası yeniden toparlanma ve etkin olma eğilimi ve ödev yapmama eğilimi değişkenlerinden oluşan akademik risk alma veri seti arasındaki ilişki kanonik korelasyon analizi ile incelenmiştir. Kanonik korelasyon analizi sonucunda, ders çalışma becerileri ve akademik risk alma arasında anlamlı ilişki tespit edilmiş ve veri setleri arasında paylaşılan ortak varyansın % 29.5 olduğu saptanmıştır.

  10. 分泌性蛋白hk10在眼睑基底细胞癌中的表达%The study of human kallikrein 10 expession in eyelid basal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    王大庆; 罗清礼

    2012-01-01

    目的:研究在眼睑基底细胞癌(basal cell carcinoma,BCC)中NES1基因的分泌蛋白(human kallikrein 10,hk10)的表达情况,并分析其表达与表型之间的关系,从蛋白水平上研究NES1在BCC的发生发展过程中的作用.方法:采用免疫组化的方法检测hk10在31例眼睑BCC中表达情况,并分析其表达与表型之间的关系,采用Image-Pro Plus5.0图像分析系统对免疫组化结果进行扫描,定量分析hk10在不同组眼睑BCC中的表达.结果:免疫组化结果显示hk10主要表达在细胞浆中,呈棕黄色.在正常眼睑上皮组织中,hk10主要分布在上皮各层的鳞状上皮细胞胞浆中,靠近基底细胞层表达稍强;BCC原发组与BCC复发组在平均光密度上无显著性差异(P>0.05),在累积光密度(IOD)上,二者的差异具有统计学意义,BCC原发组具有较强的表达.结论:hk10在正常眼睑上皮组织中高表达,在眼睑基底细胞癌(BCC)中,hk10明显表达下调;NES1阳性表达细胞的减少,可能在眼睑BCC的复发中起一定作用;NES1作为一种新的抑癌基因,其可以作为眼睑BCC的肿瘤分子标记.

  11. The role of bovine high-molecular-weight (HMW) kininogen in contact-mediated activation of bovine factor XII: interaction of HMW kininogen with kaolin and plasma prekallikrein.

    Science.gov (United States)

    Ikari, N; Sugo, T; Fujii, S; Kato, H; Iwanaga, S

    1981-06-01

    Previous studies from our laboratories (Sugo et al. (1980) Biochemistry 19, 3215-3220) have shown that bovine high-molecular-weight (HMW) kininogen remarkably accelerates the kaolin-mediated activation of Factor XII in the presence of prekallikrein, and that both fragment 1.2 and the light chain regions located in the COOH terminal half of the kininogen molecule are essential for the activation. In the present study, we demonstrate that the accelerating effect of HMW kininogen is mediated through its adsorption on the kaolin surface through the fragment 1.2 region and its complex formation with prekallikrein through the light chain region. The evidence is as follows: 1. HMW kininogen radio-labeled with 125I was adsorbed on kaolin and the adsorption was inhibited by the prior treatment of kaolin with fragment 1.2, fragment 1.2-light chain, kinin-free protein or HMW kininogen, but not with kinin- and fragment 1.2-free protein, light chain or low molecular-weight (LMW) kininogen. 2. The complex formation of HMW kininogen with prekallikrein in bovine plasma or in the purified system was examined by gel-filtration on a column of Sephacryl S-200 In bovine plasma, prekallikrein was eluted in the same fraction as HMW kininogen, showing an apparent molecular weight of 250,000, whereas purified prekallikrein was eluted in the fraction corresponding to an apparent molecular weight of 100,000. When purified prekallikrein was mixed with purified HMW kininogen in a mol ratio of 1 to 2, all prekallikrein was found to be associated with HMW kininogen. Furthermore, purified prekallikrein mixed with kininogen derivatives, such as kinin- and fragment 1.2-free protein, fragment 1.2-light chain or light chain, was eluted in the higher molecular weight fraction. HMW kininogen did not form a complex with prekallikrein. Using the same technique, it was shown that kinin- and fragment 1.2-free protein forms a complex not only with prekallikrein but also with kallikrein.

  12. THE ACTIVITY OF PROTEOLYTIC ENZYMES AND THEIR INHIBITORS IN THE SECRETION OF THE PROSTATE IN ITS BENIGN HYPERPLASIA AND CANCER

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    M. I. Kogan

    2011-01-01

    Full Text Available Background. Prostate-specific antigen is the most commonly used serum marker for the early detection of prostate cancer (PC. However, the specificity of the test is low and accounts for about 20%. The study of the regulatory functions of proteinases and their inhibitors in carcinogenesis is promising in terms of developing methods for the early cancer diagnosis.Objective: to analyze impaired proteolytic processes in the secretion of the prostate in its benign hyperplasia (BPH and PC, by determining the key indicators of the kallikrein-kinin and renin-angiotensin systems and the activity of leukocyte elastase in the prostatic secretion.Subjects and methods. Group 1 included 20 patients with PC (mean age 62.7±2.3 years. Group 2 comprised 20 men with BPH (mean age 62.2±1.4 years. A control group consisted of 20 healthy men (mean age 35.6±4.5 years. The prostatic secretions from the patients of all the groups were used to estimate the indicators of proteolytic systems: kallikrein activity, prekallikrein levels, the inhibitory activity of α1-proteinase inhibitor (α1-PI, and α2-macroglobulin (α2-MG, and the activity of angiotensin-converting enzyme (ACE and elastase and elastase-like activity.Results. Comparative analysis of the specific features of impaired proteolytic processes during benign and malignant prostate processes indicated that in PC the prostatic secretion showed a 39.2% increase in the activity of kallikrein (p < 0.001 and a 41.3% reduction in that of ACE (p < 0.001 as compared to those in BPH, which seems to reflect a decrease in prostatic secretion angiotensin II levels. PC is characterized by a drastic rise in the inhibitory potential of prostatic secretion; for the prostatic secretion activities of α1-PI and α2-MG are 56.9 (p < 0.001 and 96.8% (p < 0.001 respectively, higher than those in BPH. There are 2 statistically significant criteria for PC diagnosis: the activity of kallikrein and ACE with 75.0% specificity and 66

  13. 尤瑞克林对大鼠局灶性脑缺血再灌注损伤后APE/Ref-1表达的影响%Effect of Urinary kallikrein on the expression of apurinic apyrimidinic endonuclease/redox factor 1(APE/Ref-1) in cerebral tissue of rats subjected to cerebral ischemic-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    王言理; 陈晓兵; 许锁; 刘克喜; 石远峰

    2014-01-01

    ObjectiveTo investigate the effect of Urinary kallikrein on the expression of apurinic apyrimidinic endonuclease/redox factor 1 (APE/Ref-1) in rats which were subjected to reperfusion after middle cerebral artery occlusion (MCAO) for two hours. To explore the protective mechanism of Urinary kallikrein against ischemic/reperfusion brain injury.Methods 54 male Sprague-Dawley rats were randomly divided into three groups with 18 mice each group: control group (Con group), ischemic/reperfusion group (Model group), ischemic/reperfusion plus Urinary kallikrein group (URK group). Six rats from each group randomly selected were respectively subjected to the detection of APE/Ref-1 positive cell count in CA1 region of hippocampus by immunohistochernistry, the detection of cerebral infarct volume by TTC staining and the detection of the expression of protein APE/Ref-1 in hippocampus by Western blot.ResultsCompared with Con group, the levels of protein of expression of APE/Ref-1 in hippocampus significantly decreased (P<0.05), with the APE/Ref-1 positive cell count in CA3 region of hippocampus significantly lower (P<0.05), Urinary kallikreincan increase the protein of expression of APE/Ref-1 and the APE/Ref-1 positive cell count in CA1 region of hippocampus, but lower than that of Con group, Urinary kallikrein can decrease thecerebral infarct volume induced by the reperfusion after middle cerebral occlusion (MCAO).ConclusionUrinary kallikreincan increase the protein of expression of APE/Ref-1 after focal cerebral ischemia/reperfusion, that may be the other protective mechanism of Urinary kallikrein against ischemic/reperfusion brain injury.%目的:探讨尤瑞克林对大鼠局造性脑缺血再灌注损伤(I/R)后无嘌呤/无嘧啶核酸内切酶/氧化还原因子1(APE/Ref-1)表达的影响,进一步探讨尤瑞克林脑保护作用的机制。方法健康成年雄性SD大鼠54只,采用随机数字表法分为3组:空白对照组(Con组)(n=18),

  14. Correlation between Tissue Kallikrein and the Severity of Cerebral Ischemic Stroke%组织激肽释放酶与缺血性脑卒中严重程度的相关性研究

    Institute of Scientific and Technical Information of China (English)

    冯忠; 汪立松; 王希佳

    2013-01-01

    Objective To explore the relationship between tissue kallikrein ( TK ) level and the severity of cerebral ischemic stroke ( CIS ). Methods A total of 324 patients visiting the Department of Neurology of our hospital during May 2009 to May 2012 were included in the study. They were divided into NIHSS ≤12 group ( n =238 ) and NIHSS > 12 group ( n = 86 ) according to the National Institute of Health Stroke Scale ( NIHSS ). The age, sex, medical history, and personal history were recorded, and BMI, blood fat, liver and kidney function, and TK level were measured. Correlation analysis was conducted on the influencing factors and multiple regression analysis was used to explore the relationship between the influencing factors and the severity of CIS. Results The TK level in the NIHSS > 12 group was significantly lower than that in the NIHSS ≤12 group ( P 12 group were significantly higher than that in the NIHSS ≤ 12 group ( P <0. 01 ). The NIHSS was negatively correlated with the TK level ( r = -0. 425 , P =0. 038 ), and positively correlated with levels of cholesterol ( r = 0. 356, P < 0. 01 ) and triglyceride ( r = 0. 277, P < 0. 01 ). Multiple regression analysis showed that the TK level was negatively correlated ( b = - 0. 735 , t = - 0. 861, P = 0. 021 ), and levels of cholesterol ( b = 1.102, t=3.221, P =0.036) and triglyceride ( b = 1. 116, t =4.216, P =0.042) were negatively correlated with the severity of CIS. Conclusion The levels of TK, cholesterol, and triglyceride may be correlated with the severity of CIS. The lower the TK level, and the higher the levels of cholesterol and triglyceride, the more severe the CIS is.%目的 探讨组织激肽释放酶(TK)与缺血性脑卒中(CIS)严重程度的关系.方法 选择2009年5月-2012年5月在我院神经内科就诊的CIS患者324例,根据美国国立卫生研究院卒中量表评分(NIHSS)将患者分为NIHSS≤12分组238例和NIHSS>12分组86例.详细记录患者的年龄

  15. 质谱技术鉴定组织型激肽释放酶脑相关蛋白的研究%Identification of the related proteins of tissue kallikrein in brain using mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    王伟; 高秀兰; 朱健; 徐兵; 苏敬敬

    2014-01-01

    Objective It is to identify the related proteins of tissue kallikrein( TK)in brain by mass spectrometry. Meth-ods TK plasmids with full-length or no signal peptide cDNA sequence were transfected into Neuro -2a cells. The membrane proteins in Neuro-2a cells were biotinylated and Co-immunoprecipitation analysis was used with rabbit anti-GFP antibody. Then the streptavidin,horseradish peroxidase conjugate proteins specifically recognized biotinylation of proteins. Secondly,the purified TK protein and liquid supernatant from rat brain tissue were mixed and Co-immunoprecipitation analysis was used with rabbit anti-TK antibody and IgG. SDS -PAGE electrophoresis was carried out for silver staining. The differential proteins were separated for enzymolysis,mass spectrometry and subsequently data processing. The mRNA levels of differential proteins in cultured Neuro-2a cells after various concentrations of TK incubation were detected by RT-PCR. Results Two additional bands with molecular weights 64 kDa and 49 kDa,respectively,appeared in GFP-TK- full transfected group compared with GFP-TK-no and GFP transfected groups. The results from the action between the purified TK protein and liquid supernatant from rat brain tissue showed one additional band with anti-TK antibody. Its molecular weight was about 64 kDa. Nineteen dif-ferential proteins had been identified using mass spectrometry analysis. The mRNA levels of Homer1b/c and Flotllin-2 were up-regulated upon TK treatment in a concentration-dependent manner. Conclusion The molecular weights of TK-related pro-teins in brain were about from 40 to 65 kDa using mass spectrometry analysis. The function mechanism of TK in brain was probably associated with Homer1b/c and Flotillin-2.%目的:采用质谱技术鉴定组织型激肽释放酶( TK)的脑相关蛋白。方法将含全长、无信号肽的 TK基因质粒转染生物素标记 Neuro-2a细胞,细胞裂解液用兔源性抗 GFP抗体进行免疫共沉淀,特异性

  16. A Decade of Change: Recent Developments in Pharmacotherapy of Hereditary Angioedema (HAE).

    Science.gov (United States)

    Bork, Konrad

    2016-10-01

    Hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency (HAE-C1-INH) is a rare but medically significant disease that can be associated with considerable morbidity and mortality. Research into the pathogenesis of HAE-C1-INH has expanded greatly in the last six decades and has led to new clinical trials with novel therapeutic agents and treatment strategies. Mechanisms of pharmacotherapy include (a) supplementing C1-INH, the missing serine-protease inhibitor in HAE; (b) inhibiting the activation of the contact system and the uncontrolled release of proteases in the kallikrein-kinin system, by blocking the production/function of its components; (c) inhibiting the fibrinolytic system by blocking the production/function of its components; and (d) inhibiting the function of bradykinin at the endothelial level. Strategies for managing HAE-C1-INH are aimed at treating acute attacks, or preventing attacks, through the use of prophylactic treatment. Available agents for treating acute attacks include plasma-derived C1-INH concentrates, a recombinant C1-INH, a bradykinin B2 receptor antagonist, and a plasma kallikrein inhibitor. Long-term prophylactic treatments include attenuated androgens, plasma-derived C1-INH concentrates, and anti-fibrinolytics. Plasma-derived C1-INH and a bradykinin B2 receptor antagonist are already approved for self-administration at home. The number of management options for HAE-C1-INH has increased considerably within the past decade, thus helping to alleviate the burden of this rare disease.

  17. Dose dependence of endotoxin-induced activation of the plasma contact system: an in vitro study.

    Science.gov (United States)

    Roeise, O; Bouma, B N; Stadaas, J O; Aasen, A O

    1988-12-01

    The dose and time dependence of endotoxin-induced activation of the plasma contact system have been studied. Citrated pool plasma was incubated at 37 degrees C with endotoxin doses of 2.10(5), 2.10(6), 2.10(7), and 2.10(9) ng/l (lipopolysaccharide B, E. coli 026: B6, Difco Laboratories, Detroit, MI) for 24 hr. Samples for determination of components of the contact system were obtained prior to incubation and at 1, 2, 4, 6, 12, and 24 hr. Plasma kallikrein (KK) activity markedly increased at 12 hr in test plasma containing the highest dose of endotoxin (2.10(9) ng/l). Coincident with the elevated KK activity, reductions of both plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) were seen as assayed by chromogenic peptide substrate analyses. Also, functionally determined alpha 2-macroglobulin (alpha 2-M) and C1 inhibitor (C1INH) values were decreased, confirming the reduction of KKI values. Changes of Hageman factor (FXII), PKK, and high molecular weight kininogen (HMWK) values were also found at the same time point when assayed by immunochemical techniques. The same pattern of changes was seen in test plasma containing 2.10(7) and 2.10(6) ng/l of endotoxin. These changes, however, were less pronounced and not seen until 24 hr after beginning incubation. In control plasma and in plasma containing the lowest dose of endotoxin (2.10(5) ng/l), no changes were seen in any factors of the contact system. Our study shows that in vitro endotoxin-induced activation of the contact system is a slow process that is both time and dose dependent.

  18. Enhanced Ca(2+) response and stimulation of prostaglandin release by the bradykinin B2 receptor in human retinal pigment epithelial cells primed with proinflammatory cytokines.

    Science.gov (United States)

    Catalioto, Rose-Marie; Valenti, Claudio; Maggi, Carlo Alberto; Giuliani, Sandro

    2015-09-15

    Kallikrein, kininogen and kinin receptors are present in human ocular tissues including the retinal pigment epithelium (RPE), suggesting a possible role of bradykinin (BK) in physiological and/or pathological conditions. To test this hypothesis, kinin receptors expression and function was investigated for the first time in human fetal RPE cells, a model close to native RPE, in both control conditions and after treatment with proinflammatory cytokines. Results showed that BK evoked intracellular Ca(2+) transients in human RPE cells by activating the kinin B2 receptor. Pretreatment of the cells with TNF-α and/or IL-1β enhanced Ca(2+) response in a time- and concentration-dependent additive manner, whereas the potency of BK and that of the selective B2 receptor antagonist, fasitibant chloride, both in the nanomolar range, remained unaffected. Cytokines have no significant effect on cell number and viability and on the activity of other GPCRs such as the kinin B1, acetylcholine, ATP and thrombin receptors. Immunoblot analysis and immunofluorescence studies revealed that cytokines treatment was associated with an increase in both kinin B2 receptor and COX-2 expression and with the secretion of prostaglandin E1 and E2 into the extracellular medium. BK, through activation of the kinin B2 receptor, potentiated the COX-2 mediated prostaglandin release in cytokines-primed RPE cells while new protein synthesis and prostaglandin production contribute to the potentiating effect of cytokines on BK-induced Ca(2+) response. In conclusion, overall data revealed a cross-talk between the kinin B2 receptor and cytokines in human RPE in promoting inflammation, a key feature in retinal pathologies including diabetic retinopathy and macular edema.

  19. Bradykinin promotes migration and invasion of human immortalized trophoblasts

    Directory of Open Access Journals (Sweden)

    Lisboa Francisco

    2011-07-01

    Full Text Available Abstract Having demonstrated that the bradykinin B2 receptor (B2R is expressed in cells that participate in trophoblast invasion in humans and guinea-pigs, we investigated the role of bradykinin (BK on cell migration and invasion in the HTR-8/SVneo trophoblast cell line using wound healing and invasion assays. First, we documented that HTR-8/SVneo cells expressed kallikrein, B2R, B1R, MMP-2 and MMP-9 using immunocytochemistry. Incubation with BK (10.0 microMol/L for 18 hours increased the migration index 3-fold in comparison to controls or to cells preincubated with the B2R antagonist HOE-140. BK (10.0 microMol/L incubation yielded a similar number of proliferating and viable cells as controls, therefore the enhanced closure of the wound cannot be attributed to proliferating cells. Incubation with BK (10.0 microMol/L for 18 hours increased the invasion index 2-fold in comparison to controls or to cells preincubated with the antagonist of the B2R. Neither the B1R ligand Lys-des-Arg9 BK, nor its antagonist Lys-(des-Arg9-Leu8, modified migration and invasion. Further support for the stimulatory effect of B2R activation on migration and invasion is provided by the 3-fold increase in the number of filopodia per cell versus controls or cells preincubated with the B2R antagonist. Bradykinin had no effect on the cellular protein content of the B2R, nor the MMP-9 and MMP-2 gelatinase activity in the culture media varied after incubation with BK. This study adds bradykinin-acting on the B2R-to the stimuli of trophoblast migration and invasion, an effect that should be integrated to other modifications of the kallikrein-kinin system in normal and pathological pregnancies.

  20. Sexual hormones modulate compensatory renal growth and function

    Directory of Open Access Journals (Sweden)

    Pablo J. Azurmendi

    2013-12-01

    Full Text Available The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG that follows uninephrectomy (uNx is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50% while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

  1. The conversion of fibrinogen to fibrin at the surface of curliated Escherichia coli bacteria leads to the generation of proinflammatory fibrinopeptides.

    Science.gov (United States)

    Persson, Kristin; Russell, Wayne; Mörgelin, Matthias; Herwald, Heiko

    2003-08-22

    The inflammatory response to bacterial infection is the result of a complex interplay between bacterial products and host effector systems, such as the immune and complement systems. Here we show that Escherichia coli bacteria expressing fibrous surface proteins, known as curli, assemble and activate factors of the human coagulation cascade at their surface. As a result of this interaction, fibrinogen is converted to fibrin and fibrinogen-derived peptides, termed fibrinopeptides, are generated. The molecular mechanisms behind the bacteria-induced formation of fibrinopeptides were investigated and shown to be triggered by the activation of the contact system, also known as the kallikrein/kinin system or the intrinsic pathway of coagulation. Samples containing fibrinopeptides generated by the interaction between bacteria and plasma were injected into animals and the inflammatory response was monitored. We found that this treatment provoked an infiltration of white blood cells, and the induction of the proinflammatory cytokine MCP-1 at the inflamed site. Our results therefore demonstrate that activation of the coagulation system at the bacterial surface contributes to the pathophysiology of bacterial infectious diseases.

  2. Neurohumoral blood pressure regulation in lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Boscolo, P.; Carmignani, M.

    1988-06-01

    Previous human studies demonstrated that lead exposure may modify the metabolism of catecholamines and of hormones controlled by the hypothalamo-pituitary axis and may affect the kallikrein-kinin system. This paper reports unpublished data on the plasma renin activity of lead-exposed workers; these results are in agreement with those of previous human and experimental studies suggesting that the synthesis or release of renin is increased after short and moderate exposure to inorganic lead and reduced whenever the exposure is prolonged. Previous experimental investigations demonstrated that lead may act on the cardiovascular system, with effects on the renin-angiotensin system, on the reactivity to stimulation of peripheral catecholaminergic receptors, on sympathetic and vagal tone, and on reactivity to the stimulation of baroreceptors. This paper reports the results of a study on male Sprague-Dawley rats that received 0, 15, 30, and 60 ..mu..g/mL of lead in drinking water for 18 months. Blood pressure was increased in the rats receiving 30 and 60 ppm of lead; cardiac inotropism was augmented only in those receiving the higher dose of the metal, and heart rate was not modified. Cardiovascular responses to agonists indicated that lead exposure affects the renin-angiotensin system and induces sympathetic hyperactivity be acting on central and peripheral sympathetic junctions increasing the responsiveness to stimulation of ..cap alpha../sub 2/-adrenoreceptors and by increasing the reactivity to stimulation of cardiac and vascular ..beta..-adrenergic and dopaminergic receptors.

  3. Effects of endothelin on hemodynamics, prostaglandins, blood coagulation and renal function.

    Science.gov (United States)

    Schulz, E; Ruschitzka, F; Lueders, S; Heydenbluth, R; Schrader, J; Müller, G A

    1995-03-01

    The interaction of the endogenous vasoconstrictors endothelin (ET), angiotensin II (Ang II) and catecholamines with the kallikrein-kinin-, prostaglandin and renin-aldosterone systems in the pathogenesis of acute renal failure (ARF) is still to be defined. In 18 anesthesized pigs the influence of i.v. bolus applications of ET (2 micrograms/kg), Ang II (10 micrograms/kg) and norepinephrine (NE; 20 micrograms/kg) on hemodynamics, plasmatic coagulation and fibrinolysis system, prostaglandins and renal function was studied. ET induced a biphasic change in blood pressure, starting with an initial short-lasting reduction followed by a long-lasting elevation of systolic and diastolic blood pressure. Endothelin bolus resulted in a significant increase of 6-keto-PGF1 alpha, PGE2 and TXB2 plasma levels (P PKK) and factor VIII activity at the beginning. Finally a pronounced decrease of ATIII, FM and PKK occurred, indicating a consumptive coagulopathy. At the end of the experiment, elevated plasma renin activity and pCO2, significantly decreased creatinine clearance, blood pH, pO2, base excess, HCO3-, oxygen saturation (P < 0.01), a distinct glomerular proteinuria, and a final anuria were observated. These results reveal that ET activates the plasmatic coagulation system and induces an ARF accompanied by impairment of pulmonary function.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Impact of angiotensin and endothelin converting enzymes and related bradykinin on renal functions in L-NAME hypertensive rats

    Science.gov (United States)

    Omar, Ali Zainal; Maulood, Ismail M.

    2017-09-01

    The renin-angiotensin system (RAS), one of the most important hormonal systems, controls the kidney functions by regulating fluid volume, and electrolyte balance. The current study included the effects of kinin-kallikrein system (KKS) and its interaction with both angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE) on some of kidney function test parameters. In the present experiment, rats were divided into six groups, the first group was infused with normal saline, the second group was L-NG-Nitroarginine methyl ester (L-NAME) treated rats, third group was bradykinin (BK), forth group was captopril (ACEi), fifth group was phosphoramidon (ECEi), sixth group was a combination of BK with phosphoramidon. L-NAME was intravenously infused for one hour to develop systematic hypertension in male rats. After one hour of infusion, the results showed that L-NAME significantly increased serum creatinine. While, it decreased glomerular filtration rate (GFR), and K+ excretion rate. Moreover, BK increased packed cell volume PCV%, serum creatinine and K+ ion concentration. While, it reduced GFR, serum Ca+2 ion concentration, K+ and Na+ excretion rates. On the other hand, captopril infusion showed its effect by reduction in GFR, serum Ca+2 ion and electrolyte excretion rates. Phosphoramidon an ECEi dramatically reduced serum Ca+2 ion, but it increased pH, GFR and Ca+2 excretion rate. The results suggested that BK and Captopril each alone severely reduces GFR value. Interestingly, inhibition of ET-1 production via phosphoramidon could markedly elevate GFR values.

  5. Factor XII: a novel target for safe prevention of thrombosis and inflammation.

    Science.gov (United States)

    Kenne, E; Nickel, K F; Long, A T; Fuchs, T A; Stavrou, E X; Stahl, F R; Renné, T

    2015-12-01

    Plasma protein factor XII (FXII) activates the procoagulant and proinflammatory contact system that drives both the kallikrein-kinin system and the intrinsic pathway of coagulation. When zymogen FXII comes into contact with negatively charged surfaces, it auto-activates to the serine proteaseactivated FXII (FXIIa). Recently, various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, polyphosphate and nucleic acids. Murine models have established a central role of FXII in arterial and venous thrombosis. Despite its central function in thrombosis, deficiency in FXII does not impair haemostasis in animals and humans. In a preclinical cardiopulmonary bypass system in large animals, the FXIIa-blocking antibody 3F7 prevented thrombosis; however, in contrast to traditional anticoagulants, bleeding was not increased. In addition to its function in thrombosis, FXIIa initiates formation of the inflammatory mediator bradykinin. This mediator increases vascular leak, causes vasodilation, and induces chemotaxis with implications for septic, anaphylactic and allergic disease states. Therefore, targeting FXIIa appears to be a promising strategy for thromboprotection without associated bleeding risks but with anti-inflammatory properties.

  6. 前列腺癌组织中人腺体激肽释放酶2基因表达值与Gleason评分的相关性分析%Correlation of Gleason grading with human glandular kallikrein 2 gene expression value in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    毕学成; 何慧婵; 戴奇山; 邹钧; 韩兆冬; 梁宇翔; 叶永康; 曾国华; 钟惟德

    2008-01-01

    目的探讨人腺体激肽释放酶(hK)2基因表达值与前列腺癌的Gleason评分的相关性及临床意义.方法运用实时荧光定量(FQ)PCR方法检测40例已知Gleason评分前列腺癌病理组织中hK2的基因表达值.结果前列腺癌组织中hK2基因表达值在不同的Gleason评分中有差异,随Gleason评分值升高而升高.结论前列腺癌组织中hK2基因表达值与Gleason评分呈正相关;hK2有望成为前列腺癌早期诊断,恶性程度评估以及预后判断的重要指标.%Objective To investigate the correlation of human glandular kallikrein (hK)2 gene expression value with Gleason histologic grading and its clinical significance in prostate cancer. Methods hK2 gene expression of the cancer tissue was measured in 40 cases of prostate cancer. The Gleason histologic grading was based on histopathologic examination. Results The prostatic cancer hK2 gene expression values variated in different Gleason score. The hK2 gene expression values increased with the enhancement of Gleason scores. Conclusions The hK2 expression value is positively correlated with Gleason scores. The hK2 expression value may be an important indicator of the diagnosis, degree of malignancy and prognosis in prostate cancer.

  7. 尤瑞克林联合胞二磷胆碱治疗急性脑梗死100例的临床观察%Clinical observation of 100 cases of acute cerebral infarction of Kallikrein joint citicoline treatment

    Institute of Scientific and Technical Information of China (English)

    赵健

    2015-01-01

    Objective Observed rachlin joint citicoline treatment of acute cerebral infarction clinical efficacy of 100 cases and analyzed.Methods 100 patients were randomLy divided into two groups, the treatment group of 50 patients with a control group of 50 patients in the control group underwent conventional treatment, the treatment group Uribe clindamycin combined citicoline treatment, were treated for 21 days.Results The treatment group was more significant effect than the control group, 50 patients were cured in 8 cases, 30 cases markedly effective, 10 cases effective, the total efficiency of 96%.Conclusion Kallikrein joint citicoline clinical efficacy of treatment of acute cerebral infarction satisfaction, worthy of clinical application.%目的:观察尤瑞克林联合胞二磷胆碱治疗急性脑梗死100例的疗效并加以分析。方法将100例患者随机分为两组,治疗组50例与对照组50例,对照组行常规治疗,治疗组加用尤瑞克林联合胞二磷胆碱治疗,两组疗程均为21天。结果治疗组较对照组疗效更显著,50例患者中治愈8例,显效30例,有效10例,总有效率96%。结论尤瑞克林联合胞二磷胆碱治疗急性脑梗死的疗效满意,值得临床推广应用。

  8. First Report of Eurycoma longifolia Jack Root Extract Causing Relaxation of Aortic Rings in Rats

    Science.gov (United States)

    2016-01-01

    Although Eurycoma longifolia has been studied for erectile function, the blood pressure- (BP-) lowering effect has yet to be verified. Hence, this study aims at investigating the BP-lowering properties of the plant with a view to develop an antihypertensive agent that could also preserve erectile function. Ethanolic root extract was partitioned by hexane, dichloromethane (DCM), ethyl acetate, butanol, and water. The DCM fraction, found to be potent in relaxing phenylephrine- (PE-) precontracted rat aortic rings, was further purified by column chromatography. Subfraction DCM-II, being the most active in relaxing aortae, was studied for effects on the renin-angiotensin and kallikrein-kinin systems in aortic rings. The effect of DCM-II on angiotensin-converting enzyme (ACE) activity was also evaluated in vitro. Results showed that DCM-II reduced (p < 0.05) the contractions evoked by angiotensin I and angiotensin II (Ang II). In PE-precontracted rings treated with DCM-II, the Ang II-induced contraction was attenuated (p < 0.05) while bradykinin- (BK-) induced relaxation enhanced (p < 0.001). In vitro, DCM-II inhibited (p < 0.001) the activity of ACE. These data demonstrate that the vasodilatory effect of DCM-II appears to be mediated via inhibition of Ang II type 1 receptor and ACE as well as enhancement of Ang II type 2 receptor activation and BK activity.

  9. Insight into the interactive residues between two domains of human somatic Angiotensin-converting enzyme and Angiotensin II by MM-PBSA calculation and steered molecular dynamics simulation.

    Science.gov (United States)

    Guan, Shan-shan; Han, Wei-wei; Zhang, Hao; Wang, Song; Shan, Ya-ming

    2016-01-01

    Angiotensin-converting enzyme (ACE), a membrane-bound zinc metallopeptidase, catalyzes the formation of Angiotensin-II (AngII) and the deactivation of bradykinin in the renin-angiotensin-aldosterone and kallikrein-kinin systems. As a hydrolysis product of ACE, AngII is regarded as an inhibitor and displays stronger competitive inhibition in the C-domain than the N-domain of ACE. However, the AngII binding differences between the two domains and the mechanisms behind AngII dissociation from the C-domain are rarely explored. In this work, molecular docking, Molecular Mechanics/Poisson-Boltzmann Surface Area calculation, and steered molecular dynamics (SMD) are applied to explore the structures and interactions in the binding or unbinding of AngII with the two domains of human somatic ACE. Calculated free energy values suggest that the C-domain-AngII complex is more stable than the N-domain-AngII complex, consistent with available experimental data. SMD simulation results imply that electrostatic interaction is dominant in the dissociation of AngII from the C-domain. Moreover, Gln106, Asp121, Glu123, and Tyr213 may be the key residues in the unbinding pathway of AngII. The simulation results in our work provide insights into the interactions between the two domains of ACE and its natural peptide inhibitor AngII at a molecular level. Moreover, the results provide theoretical clues for the design of new inhibitors.

  10. Hereditary Angioedema and Gastrointestinal Complications: An Extensive Review of the Literature

    Directory of Open Access Journals (Sweden)

    Napoleon Patel

    2015-01-01

    Full Text Available Hereditary Angioedema (HAE is a rare autosomal dominant (AD disease characterized by deficient (type 1 or nonfunctional (type 2 C1 inhibitor protein. The disorder is associated with episodes of angioedema of the face, larynx, lips, abdomen, or extremities. The angioedema is caused by the activation of the kallikrein-kinin system that leads to the release of vasoactive peptides, followed by edema, which in severe cases can be life threatening. The disease is usually not diagnosed until late adolescence and patients tend to have frequent episodes that can be severely impairing and have a high incidence of morbidity. Gastrointestinal involvement represents up to 80% of clinical presentations that are commonly confused with other gastrointestinal disorders such as appendicitis, cholecystitis, pancreatitis, and ischemic bower. We present a case of an HAE attack presenting as colonic intussusception managed conservatively with a C1 esterase inhibitor. Very few cases have been reported in the literature of HAE presentation in this manner, and there are no reports of any nonsurgical management of these cases.

  11. Hereditary Angioedema and Gastrointestinal Complications: An Extensive Review of the Literature

    Science.gov (United States)

    Patel, Napoleon; Suarez, Lisbet D.; Kapur, Sakshi; Bielory, Leonard

    2015-01-01

    Hereditary Angioedema (HAE) is a rare autosomal dominant (AD) disease characterized by deficient (type 1) or nonfunctional (type 2) C1 inhibitor protein. The disorder is associated with episodes of angioedema of the face, larynx, lips, abdomen, or extremities. The angioedema is caused by the activation of the kallikrein-kinin system that leads to the release of vasoactive peptides, followed by edema, which in severe cases can be life threatening. The disease is usually not diagnosed until late adolescence and patients tend to have frequent episodes that can be severely impairing and have a high incidence of morbidity. Gastrointestinal involvement represents up to 80% of clinical presentations that are commonly confused with other gastrointestinal disorders such as appendicitis, cholecystitis, pancreatitis, and ischemic bower. We present a case of an HAE attack presenting as colonic intussusception managed conservatively with a C1 esterase inhibitor. Very few cases have been reported in the literature of HAE presentation in this manner, and there are no reports of any nonsurgical management of these cases. PMID:26339513

  12. Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with multiple virulence activities.

    Science.gov (United States)

    Imamura, Takahisa; Murakami, Yoji; Nitta, Hidetoshi

    2017-09-26

    Aeromonas sobria serine protease (ASP) is secreted from Aeromonas sobria, a pathogen causing gastroenteritis and sepsis. ASP resembles Saccharomyces cerevisiae Kex2, a member of the subtilisin family, and preferentially cleaves peptide bonds at the C-terminal side of paired basic amino acid residues; also accepting unpaired arginine at the P1 site. Unlike Kex2, however, ASP lacks an intramolecular chaperone N-terminal propeptide, instead utilizes the external chaperone ORF2 for proper folding, therefore, ASP and its homologues constitute a new subfamily in the subtilisin family. Through activation of the kallikrein/kinin system, ASP induces vascular leakage, and presumably causes edema and septic shock. ASP accelerates plasma clotting by α-thrombin generation from prothrombin, whereas it impairs plasma clottability by fibrinogen degradation, together bringing about blood coagulation disorder that occurs in disseminated intravascular coagulation, a major complication of sepsis. From complement C5 ASP liberates C5a that induces neutrophil recruitment and superoxide release, and mast cell degranulation, which are associated with pus formation, tissue injury and diarrhea, respectively. Nicked two-chain ASP also secreted from A. sobria is more resistant to inactivation by α2-macroglobulin than single-chain ASP, thereby raising virulence activities. Thus, ASP is a potent virulence factor and may participate in the pathogenesis of A. sobria infection.

  13. The interaction of AGT and NOS3 gene polymorphisms with conventional risk factors increases predisposition to hypertension.

    Science.gov (United States)

    Gatti, Renata R; Santos, Paula S; Sena, Angela A S; Marangoni, Karina; Araújo, Messias A; Goulart, Luiz R

    2013-12-01

    Renin-angiotensin and kallikrein-kinin systems are interconnected, regulating blood pressure homeostasis. We have demonstrated the interactions among polymorphisms of the angiotensinogen (AGT) and endothelial nitric oxide synthase (NOS3) genes and conventional risk factors affecting the hypertension occurrence. Individuals were recruited (n=192) and classified into hypertensive (HG; n=140) and normotensive (NG; n=52) groups. The genotypic distribution of the Met235Thr (AGT) and Glu298Asp (NOS3) polymorphisms demonstrated that both are independent risk factors of hypertension (p=0.02 and p=0.008, respectively). The concomitant presence of these polymorphisms in the HG group was significantly different (p=0.001) from the NG. Both gene polymorphisms presented an additive effect for the unfavourable alleles T and A, respectively, and 95% of the double mutant homozygotes were classified into the HG. Specific interactions among certain conventional factors and the presence of at least one unfavourable allele presented significant odds towards hypertension. Blood pressure homeostasis was affected by genetic polymorphisms conditioned by the T and A alleles of the AGT and NOS3 genes, respectively, which acted independently. However, their interaction with smoking, sedentariness, age and total cholesterol may have increased the predisposition to hypertension, which may explain most of the hypertension cases.

  14. Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    List, K; Jensen, O N; Bugge, T H

    2000-01-01

    The plasminogen activation (PA) system is involved in the degradation of fibrin and various extracellular matrix proteins, taking part in a number of physiological and pathological tissue remodeling processes including cancer invasion. This system is organized as a classical proteolytic cascade, ...

  15. Investigation of relationship between pedagogical formation program students’ personality traits and attitudes towards teaching professionPedagojik formasyon öğrencilerinin kişilik özellikleri ve öğretmenlik mesleğine yönelik tutumları arasındaki ilişkinin incelenmesi

    Directory of Open Access Journals (Sweden)

    Mustafa Uslu

    2013-09-01

    Full Text Available The aim of this study is assessment of the relationship between pedagogical formation program students’ attitudes personality traits and towards teaching profession. For this purpose, in order to determine students’ personality characteristics is used Adjective Based Personality Scale (ABPT which is developed by Bacanlı, İlhan ve Aslan (2009, in order to determine pedagogical formation program students’ attitudes towards teaching profession is used Attitude Scale of Teaching Profession which is developed by Çetin (2006. The working group containing 220 female and 137 male totally 357 students is composed of graduated students attending the pedagogic formation education in Selcuk University in the academic year of fall and spring in 2012-2013. According to the analyzed of the research is found a relationship between students ‘attitudes towards teaching profession and personality traits in terms of openness to experience, extraversion, agreeableness and conscientiousness, there is a meaningful and positive relation the level of .05. Özet Bu araştırmanın amacı; pedagojik biçimlenme programı öğrencilerinin kişilik özellikleri ile mesleğe yönelik tutumları arasındaki ilişkinin incelenmesidir. Bu amaç doğrultusunda öğrencilerin kişilik özelliklerini belirlemek için Bacanlı, İlhan ve Aslan (2009 tarafından geliştirilen “Sıfatlara Dayalı Kişilik Testi (SDKT”, formasyon öğrencilerinin mesleğe yönelik tutumlarını belirlemek amacı için ise, Çetin (2006 tarafından geliştirilen “Öğretmenlik Mesleğine Yönelik Tutum Ölçeği (ÖMTÖ” kullanılmıştır. Araştırma örneklemi Selçuk Üniversitesinde pedagojik formasyon eğitimine devam eden, 357 öğrenciden oluşmuştur (220 bayan, 137 erkek. Veriler 2012-2013 bahar ve güz döneminde, toplanmış ve analiz edilmiştir. Araştırmada yapılan istatistiksel analizler sonucunda kişilik özellikleri ve mesleğe yönelik tutum arasında d

  16. Examination of relationship between communication skills, burnout levels and life satisfaction levels of football coaches Futbol antrenörlerinin iletişim becerileri, tükenmişlik düzeyleri ve yaşam tatminleri arasındaki ilişkinin incelenmesi

    Directory of Open Access Journals (Sweden)

    Yakup Akif Afyon

    2013-06-01

    Full Text Available The purpose of this study is to examine the relationship between burnout levels, communication skills and life satisfaction levels of football coaches. A survey was applied to 120 football coaches who attended to Football Coach Development Seminar that was held in July 2012 in Muğla and 80 surveys were evaluated after removing 40 incorrect surveys. As a result, a negative relationship (r=-.293, p<,05 was determined between communication skills and emotional burnout levels of football coaches. A positive relationship (r=.280, p<,05 was found between coaches' life satisfaction levels and the variable of age and a negative relationship (r=-.275, p<,05 was found between coaches' life satisfaction levels and their education levels. In addition, a negative relationship (r=-.295, p<,05 was observed between football coaches' communication skills and life satisfaction levels. These results show us that the higher communication skills of coaches decrease their occupational burnout levels but increase their life satisfaction levels. Özet Bu çalışmanın amacı, futbol antrenörlerinin tükenmişlik düzeyleri, iletişim becerileri ve yaşam tatminleri arasındaki ilişkinin incelenmesidir. Muğla ilinde 2012 Temmuz ayında düzenlenen Futbol Antrenör Gelişim Seminerine katılan 120 antrenöre, anket uygulaması yapılmış, hatalı 40 anket çıkartılarak, 80 anket değerlendirmeye alınmıştır. Sonuç olarak; futbol antrenörlerinin iletişim becerileri ile duygusal tükenmişlik düzeyleri arasında negatif (r=-.293, p<,05 bir ilişki saptanmıştır. Antrenörlerin yaşam tatmin düzeyleri ile yaş değişkeni arasında pozitif (r=.280, p<,05, eğitim durumları arasında ise negatif bir ilişki (r=-.275, p<,05 bulunmuştur. Ayrıca futbol antrenörlerinin iletişim becerileri ile yaşam tatmin düzeyleri arasında negatif (r=-.295, p<,05 bir ilişki vardır. Bu sonuçlar bize, antrenörlerin iletişim becerilerinin yükseldikçe mesleki t

  17. The complement system in human cardiometabolic disease.

    Science.gov (United States)

    Hertle, E; Stehouwer, C D A; van Greevenbroek, M M J

    2014-10-01

    The complement system has been implicated in obesity, fatty liver, diabetes and cardiovascular disease (CVD). Complement factors are produced in adipose tissue and appear to be involved in adipose tissue metabolism and local inflammation. Thereby complement links adipose tissue inflammation to systemic metabolic derangements, such as low-grade inflammation, insulin resistance and dyslipidaemia. Furthermore, complement has been implicated in pathophysiological mechanisms of diet- and alcohol induced liver damage, hyperglycaemia, endothelial dysfunction, atherosclerosis and fibrinolysis. In this review, we summarize current evidence on the role of the complement system in several processes of human cardiometabolic disease. C3 is the central component in complement activation, and has most widely been studied in humans. C3 concentrations are associated with insulin resistance, liver dysfunction, risk of the metabolic syndrome, type 2 diabetes and CVD. C3 can be activated by the classical, the lectin and the alternative pathway of complement activation; and downstream activation of C3 activates the terminal pathway. Complement may also be activated via extrinsic proteases of the coagulation, fibrinolysis and the kinin systems. Studies on the different complement activation pathways in human cardiometabolic disease are limited, but available evidence suggests that they may have distinct roles in processes underlying cardiometabolic disease. The lectin pathway appeared beneficial in some studies on type 2 diabetes and CVD, while factors of the classical and the alternative pathway were related to unfavourable cardiometabolic traits. The terminal complement pathway was also implicated in insulin resistance and liver disease, and appears to have a prominent role in acute and advanced CVD. The available human data suggest a complex and potentially causal role for the complement system in human cardiometabolic disease. Further, preferably longitudinal studies are needed to

  18. Clinical effect of urinary kallikrein in the treatment of progressive cerebral infarction and its influence on hs-CRP%尤瑞克林治疗进展性脑梗死的临床疗效及对血清超敏 C-反应蛋白的影响

    Institute of Scientific and Technical Information of China (English)

    邱峥; 林力; 何必华

    2016-01-01

    目的探讨尤瑞克林在进展性脑梗死患者中的临床疗效及对血清超敏 C-反应蛋白(hs-CRP)的影响。方法92例进展性脑梗死患者采用数字表法随机分为观察组(n =46)与对照组(n =46),对照组给予常规治疗,观察组在对照组基础上加用尤瑞克林治疗,比较两组临床疗效及对血清 hs-CRP 的影响。结果观察组显效率为71.7%,有效率为89.1%,均显著高于对照组的43.5%与69.6%(χ2=7.5220、5.3727,P <0.05或 P <0.01);治疗后两组 hs-CRP 分别为(11.79±3.92)mmol/L 与(10.04±3.90)mmol/L,均显著低于治疗前的(13.48±3.89)mmol/L 与(13.54±3.93)mmol/L(t =4.2874、2.0755,P <0.05或 P <0.01),且治疗后观察组显著低于对照组(t =2.1465,P <0.05);治疗后两组 NIHSS 评分分别为(9.91±4.35)分与(6.82±4.32)分,均显著低于治疗前的(15.39±4.34)分与(15.43±4.37)分(t =6.0486、9.5032,均 P <0.01),且观察组显著优于对照组(t =3.4185,P <0.01);治疗后两组 Barthel 指数分别为(53.87±18.12)与(68.21±18.14),均显著高于治疗前的(34.35±18.08)与(34.42±18.11)(t =5.1721、8.9434,均 P <0.01),且观察组显著优于对照组(t =3.7933,P <0.01);两组治疗过程中均未见明显不良反应。结论尤瑞克林用于进展性脑梗死的治疗,能有效改善局部血流灌注,恢复神经功能损伤,提高患者生活能力,疗效确切,安全可靠,值得推广。%Objective To discuss the clinical effect of urinary kallikrein in the treatment of progressive cerebral infarction and its influence on hs -CRP.Methods 92 patients with progressive cerebral infarction were ran-domly divided into the observation group(n =46)and the control group(n =46)according to the

  19. Peritoneal lavage efficiently eliminates protease-alpha-2-macroglobulin complexes and components of the contact system from the peritoneal cavity in patients with severe acute pancreatitis.

    Science.gov (United States)

    Aasen, A O; Ruud, T E; Roeise, O; Bouma, B N; Stadaas, J O

    1989-01-01

    Trypsin (Try), plasma kallikrein (KK) and plasmin activities together with coagulation factor XII (F XII, Hageman factor), high-molecular-weight kininogen (HMWK), plasma prekallikrein (PKK), alpha 2-macroglobulin (alpha 2-M), C1 inhibitor (C1Inh), and functional plasma kallikrein inhibition (KKI) values were studied in peritoneal fluid and lavage taps of 9 patients with severe acute pancreatitis treated with peritoneal lavage. Both immunochemical methods and functional techniques based on chromogenic peptide substrate assays were used. In the exudate obtained before peritoneal lavage was performed, F XII was 52%, HMWK was 30%, PKK was 40%, alpha 2-M was 29% and C1Inh was 57% of standard plasma pool values, determined by immunochemical technique. Functional plasma KKI values were zero, whereas Try activities determined by chromogenic peptide substrate technique were markedly elevated in the exudate. Using a prepacked HR 10/30 Superose Tm 12 column (Pharmacia, Uppsala, Sweden) and chromogenic peptide substrate assays, Try and KK activities were detected in the alpha 2-M containing fractions of the peritoneal exudate demonstrating KK-alpha 2-M and Try-alpha 2-M complex formation. The peritoneal lavage procedure efficiently eliminated components of the contact system and protease activities. In the first lavage tap, Try activities were markedly reduced compared to values found in the exudate and concentrations of F XII, HMWK, PKK, alpha 2-M and C1Inh were all zero. In consecutive lavage taps Try values were also zero. The study shows that the lavage procedures efficiently clears the peritoneal cavity for protease-alpha 2-M complexes generated during acute pancreatitis. Also, components of the contact system found in peritoneal exudate, and which might serve as substrates for the protease-alpha 2-M complexes, are rapidly eliminated by the procedure.

  20. Investigation of the relationship between problematic internet use and psychological symptoms of science high school studentsFen lisesi öğrencilerinin problemli internet kullanımı ile psikolojik semptomları arasındaki ilişkinin incelenmesi

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    Zöhre Kaya

    2016-01-01

    Full Text Available In this study, investigation of level of problematic internet use and psychological symptoms of 538 science high school students reciving education in Van and Izmir cities was aimed. At the same time, it was examined that according to being day or boarding student and gender whether the level of problematic internet use and psychological symptoms of students differ or not. The data collected eith Brief Symptom Inventory (BSI and Problematic Internet Use Adolscent Form (PIU-A. Data analysis was carried out through SPSS 15.00 statistical package programme. In analysis Spearman Brown correlation coefficient and Mann Whitney U test were used. According to obtained findings, there was stastistically significant and positive relationship between problematic internet use and psychological symptoms of science high school students. Negative self and somatization socres of day students were higher than broading students. It was found that the level of problematic internet use of boarding students were higher than boarding students. According to gender, it was found that females had higher score than males on four subscale of BSI (anxiety, depression, negative self and somatization and males had higher score than females on social benefits subscale of PIU-A. Obtained results were discussed in the light of related literature and suggestions were offered.   Özet Bu çalışmada, Van ve İzmir illerinde öğrenim gören 538 fen lisesi öğrencisinin problemli internet kullanım düzeyleri ile psikolojik semptomları arasındaki ilişkinin incelenmesi amaçlanmıştır. Aynı zamanda problemli internet kullanımının ve psikolojik semptomların öğrencilerin yatılı, gündüzlü olma durumu ile cinsiyet değişkenine göre farklılaşıp farklılaşmadığı da incelenmiştir. Araştırmanın verileri Kısa Semptom Envanteri (KSE ve Problemli İnternet Kullanımı Ölçeği-Ergen (PİKÖ-E formu ile toplanmıştır. Veri analizi SPSS 15.00 istatistik

  1. An investigation of the relationship between positive and negative perfectionism and study skills with canonical correlationOlumlu ve olumsuz mükemmeliyetçilik ile ders çalışma becerileri arasındaki ilişkinin kanonik korelasyon ile incelenmesi

    Directory of Open Access Journals (Sweden)

    Mustafa İlhan

    2013-01-01

    Full Text Available Abstract The aim of this research was to investigate the relationships between positive and negative perfectionism and study skills. Relational screening model was used in this study with this aim. Workgroup of the investigation consists of 207 students receiving study in three high schools in Battalgazi District of Malatya City, in the spring semester of 2011-2012 school year. 105 (50.72% of the students in the workgroup are female and 102 (50.28% of whom are male. In the research, “The Positive and Negative Perfectionism Scale” developed by Kırdök (2004 has been used to determine the perfectionism characteristics of the students and “The Study Skills Scale” developed by Mr. Bay, Tuğluk and Gençdoğan (2004 has been used to test the study skills of the students. In the research, the relationship between the perfectionism data set composing of positive perfectionism and negative perfectionism variables; and study skills data set composing of motivation, time management, and exam preparation-test anxiety management variables has been investigated by canonical correlation analysis. The results of canonical correlation analysis demonstrated that there were significant relationships between positive and negative perfectionism and study skills. Common variance that the positive and negative perfectionism and study skills data sets share has been calculated as 35.59%. ÖzetBu araştırmada, olumlu ve olumsuz mükemmeliyetçilik ile ders çalışma becerileri arasındaki ilişkinin incelenmesi amaçlanmıştır. Bu amaca uygun olarak araştırmada ilişkisel tarama modeli kullanılmıştır. Araştırmanın çalışma grubu, 2011-2012 Öğretim Yılı Bahar Dönemi’nde Malatya ili Battalgazi İlçesindeki üç lisede öğrenim gören 105’i (%50.72 bayan, 102’si (%50.28 ise erkek olmak üzere toplam 207 öğrenciden oluşmaktadır. Araştırmada öğrencilerin mükemmeliyetçilik özelliklerinin belirlenmesinde Kırdök (2004 taraf

  2. Examining the relationship between university students’ lifelong learning tendencies and their self-efficacy perceptionsÜniversite öğrencilerinin yaşam boyu öğrenme eğilimleri ile özyeterlik algıları arasındaki ilişkinin belirlenmesi

    Directory of Open Access Journals (Sweden)

    Aşkın Karaduman

    2017-02-01

    zyeterlik algıları arasındaki ilişkiyi belirlemektir. Araştırma ilişkisel bir tarama modelidir. Araştırmanın çalışma grubunu 2014-2015 akademik yılında Bartın Üniversitesi'nin farklı fakültelerinde/ yüksekokulunda lisans programlarına devam eden 1. ve 4. sınıf öğrencilerinden toplam 470 katılımcı oluşturmaktadır. Araştırmada veri toplama aracı olarak Yaşam Boyu Öğrenme Eğilimlerini Belirme Ölçeği (Coşkun, 2009 ile Genellenmiş Öz-yetkinlik Beklentisi Ölçeği (Jerusalem ve Schwarzer, 1979 kullanılmıştır. Araştırma sonuçlarına göre üniversite öğrencilerinin yaşam boyu öğrenme eğilimleri yüksek düzeydedir. Yaşam boyu öğrenme eğilimi araştırmanın demografik değişkenleri açısından incelendiğinde cinsiyet, baba mesleği ve serbest zaman etkinlikleri içerisinde yer alan kitap okuma ve televizyon izleme etkinliklerinde anlamlı bir farklılık bulunmuştur. Bu anlamlı farklılığın kızların, babası muhasebeci olanların, kitap okuyan ve televizyon izlemeyen üniversite öğrencileri lehine olduğu görülmüştür. Araştırma sonuçlarına göre üniversite öğrencilerinin özyeterlik algılarının da yüksek düzeyde olduğu tespit edilmiştir. Özyeterlik algıları araştırmanın demografik değişkenleri açısından incelendiğinde cinsiyet, fakülte/yüksekokul ve serbest zaman etkinlikleri içerisinde yer alan kitap okumama ve sinemaya gitme etkinliklerinde anlamlı bir farklılık bulunmuştur.  Anlamlı farklılığın erkeklerin,  Beden Eğitimi ve Spor Yüksekokulu öğrencilerinin, kitap okumayan ve sinemaya giden üniversite öğrencilerinin lehine olduğu görülmüştür.  Üniversite öğrencilerinin yaşam boyu öğrenme eğilimleri ile özyeterlik algıları arasında pozitif yönde anlamlı bir ilişkinin olduğu tespit edilmiştir.

  3. 组织激肽释放酶基因多态性A1789G 对高血压患者血浆肌酐水平的影响%Effects of human tissue kallikrein gene A1789G polymorphism on plasma creatinine levels in patients with essential hypertension

    Institute of Scientific and Technical Information of China (English)

    洪宗元; 张秀清; 黄帼; 凌代俊; 徐希平

    2005-01-01

    AIM: To investigate the effect of the human tissue kallikrein gene (hKLK1) polymorphism on plasma creatinine levels in hypertensive subjects. METHODS: The hKLK1 A1789G polymorphism was genotyped by PCR-restriction fragment length polymorphism (RFLP) in 733 hypertensive subjects. The relationship between genotype and plasma creatinine level was performed by a multiple regression analysis. The interactive effect of genotype and blood pressure on the plasma creatinine level was accessed by ANOVA. RESULTS: Multiple regression analysis showed that the plasma creatinine level was significantly higher in the subjects with mutant allele G (AG or GG genotype) than in those with wild allele A (AA genotype) (P=0.009 and P=0.046, respectively). ANOVA indicated that the AG and GG genotype individuals had high plasma creatinine levels in SBP and DBP Compared with AA genotype individuals, and the plasma creatinine level increased with blood pressure rises (P<0.05). CONCLUSION: The hKLK1 A1789G polymorphism influences plasma creatinine level, and the A1789→G variation is a risk factor in renal plasma creatinine clearance rate decline in hypertensive individuals.%目的:探讨组织激肽释放酶基因多态性对高血压患者血浆肌酐水平的影响.方法:用聚合酶链反应-限制性片段长度多态性( PCR-RFLP)方法对 733 例高血压患者的组织激肽释放酶基因 A1789G 多态位点进行基因分型,用线性回归模型分析基因型与血浆肌酐水平之间的关系,用方差分析分析基因型和血压对血浆肌酐水平的交互影响.结果:携带突变型等位基因1789G(基因型AG或GG)高血压患者较携带野生型等位基因A1789(基因型AA)患者的血浆肌酐水平明显升高,且血浆肌酐水平随着血压的升高而升高.结论:组织激肽释放酶基因多态性对高血压患者的血浆肌酐水平产生明显影响,A1789G 多态位点是高血压患者血浆肌酐清除率下降的一个危险因素.

  4. Challenges posed to the maternal circulation by pregnancy

    Directory of Open Access Journals (Sweden)

    Valdés G

    2011-08-01

    cardiovascular disease in women.Keywords: renin-angiotensin-aldosterone system, prostanoids, kallikrein-kinin system, RAS, VEGF

  5. Effects of angiotensin converting enzyme inhibitor: ramipril on different biochemical parameters in essential hypertensive patients

    Directory of Open Access Journals (Sweden)

    Pratibha S. Salve

    2016-06-01

    Conclusions: Ramipril has beneficial effects on RAS (Renin angiotensin system and kinin system or both may contribute to the improvement in different biochemical parameters by ramipril. [Int J Res Med Sci 2016; 4(6.000: 2288-2291

  6. Proteomics Study on Nonallergic Hypersensitivity Induced by Compound 4880 and Ovalbumin.

    Directory of Open Access Journals (Sweden)

    Yubin Xu

    Full Text Available Nonallergic hypersensitivity reaction (NHR accounts for more than 77% of all immune-mediated immediate hypersensitivity reactions and has become a serious threat to public health. Here, proteomics was used to study the NHR mechanism of two typical substances, the compound 4880 and ovalbumin. Twelve different proteins were suggested as potential biomarkers for examining the NHR mechanism, and our results revealed that the mechanism mainly encompassed 2 processes, i.e., generation and effect processes. The generation process could be classified as direct stimulation, complement (classical and alternative, coagulation, kallikrein-kinin, and integrated pathways. Thus glutathione peroxidase 1, terminal complement complex (complement factor 4d and Bb, coagulation 13, kininogen-1, and IgE could be used as candidate biomarkers for the indication of the corresponding pathways respectively, the proteins were further confirmed by ELISA. And the effect process was mainly composed of histamine as well as proteins such as DCD and MYLPF, which could be used as important indices for the symptoms of NHR. Our study differs from previous studies in that C4880 was found to not only be involved in the direct stimulation pathway, but also in the activated complement and kallikrein-kinin pathways through the coagulation pathway. We also report for the first time that ovalbumin-induced NHR could be a combination of the coagulation, classical complement, and integrated pathways.

  7. [An orientational examination of the effects of extracts from mixtures of herbal drugs on selected renal functions].

    Science.gov (United States)

    Masteiková, R; Klimas, R; Samura, B B; Savickas, A; Samura, B A; Belaij, S I; Samura, I B; Rabisková, M; Chalupová, Z; Bernatoniene, J

    2007-04-01

    The paper aimed to determine the effects of mixtures of selected medicinal plants on some physiological renal functions, i.e. excretion of urine and electrolytes and changes in the quantity of prostaglandins E2 (PGE2) and kallikrein-kinins in rat blood plasma after water and salt load. The following medicinal plants were selected for the examination: downy birch (Betula pubescens EHRH.), everlasting flower (Helichrysum arenarium L. MOENCH.), hawthorn (Crataegus oxyacantha L.), woodland strawberry (Fragaria vesca L.), sweet corn (Zea mays L.), German chamomile (Matricaria recutita L.), and field horsetail (Equisetum arvense L.). Herbal drugs were used to compose 6 mixtures. Extracts from these mixtures were administered to Wistar strain males and their effects were compared with the effects of an administered suspension of hydrochlorothiazide, an extract from field horsetail herb alone, and a control group of animals which was not administered any preparation. The greatest diuretic effect was found in a mixture composed of birch leaves (Betulae folium), hawthorn berries (Crataegi fructus), strawberry leaves (Fragariae folium), corn silk (Maydis stigmata), chamomile flowers (Matricariae flos), and horsetail herb (Equiseti herba). Its effect was greater by 47% and 34% than the effect of a horsetail herb extract and a hydrochlorothiazide suspension (p < 0.05), respectively. The extract from this mixture also increased the quantity of prostaglandins E2 and kallikrein-kinins in rat blood plasma in water and salt load.

  8. 食源性血管紧张素转化酶抑制肽研究进展%Research progress in food-derived angiotensin converting enzyme inhibitory peptides

    Institute of Scientific and Technical Information of China (English)

    段秀; 张玉锋; 庄永亮

    2012-01-01

    Renin-angiotensin system (RAS) and kallikrein kinin system (KKS) is a pair of mutually antagonistic system in blood pressure regulation,dissonance of which is considered to be an important factor in the pathogenesis of hypertension, and angiotensin converting enzyme (ACE) is a critical factor affecting the systems. More and more attentions have been paid to the food-derived ACE inhibitory peptides,because of their higher activity of inhibiting ACE,good security,low cost,easy to absorb and obvious antihypertension . In this review,the antihypertensive mechanism,sources,bioavailability,structure-activity relationships,separation and purification methods,activity measurement,functional assessment of ACE inhibitory peptides,and its application prospects were introduced.%肾素-血管紧张素系统(RAS)和激肽释放酶-激肽系统(KKS)在血压调节方面是一对相互拮抗的体系,其平衡失调被认为是高血压发病的一个重要因素,而血管紧张素转化酶(ACE)是影响两体系的关键。食物来源的ACE抑制肽因具有安全性好、成本低、易吸收、降压明显等优点,越来越受到人们的关注。本文详尽阐述了ACE抑制肽的降压机制、来源、生物利用率、结构与活性关系、分离纯化方法、活性测定与功能评价及其应用前景。

  9. 组织激肽释放酶7在宫颈上皮内瘤样病变组织表达的分析及临床意义%Analysis and clinical significance of the expression of kallikrein 7 protein in cervical intraepithelial neoplasia tissues

    Institute of Scientific and Technical Information of China (English)

    夏震; 苏琛辉; 王晓兰; 刘育飞

    2015-01-01

    目的通过检测组织激肽释放酶7(KLK7)在不同级别宫颈病变组织中的表达,探讨KLK7在宫颈癌前病变进展中的作用,筛选高危个体,指导临床上对CIN 的个体化治疗。方法收集深圳市人民医院妇科2012至2014年手术切除标本120例,通过免疫组化方法检测CIN 组织中KLK7的表达,并以慢性宫颈炎组织,宫颈鳞癌作对照,分析宫颈癌前病变组织中 KLK7的表达水平,对其表达水平与CIN 不同级别的相关性进行分析。结果本研究证实KLK7广泛存在于CIN 的细胞浆和细胞核中,慢性宫颈炎组和CIN 组及宫颈癌组间差异有统计学意义,CIN 分级后有显著性差异。高级别CIN 及宫颈癌中KLK7阳性率显著高于低级别CIN 及慢性宫颈炎。慢性宫颈炎组织中KLK7有表达,但阳性结果中以低表达为主,阳性率52.5%。且随着CIN 级别升高,阳性细胞数显著增多,染色逐渐加深,阳性率从CIN1的77.5%增加到CIN3的97.5%。结论 KLK7在 CIN 的发生、发展连续过程中的表达逐渐增强,可能参与宫颈癌前病变的发生发展,KLK7高表达可能与宫颈癌发生相关。KLK7检测可能预测宫颈癌前病变预后。%Objective Through the detection of kallikrein 7 (KLK7) expression in different grades of cervical lesion tissues,to explore the role of KLK7 in the development of cervical precancerous lesion,screening of high-risk individuals,individual guide the clinical treatment for CIN. Methods Paraffin sections of 120 cases were collected,the expression of KLK7 by immunohistochemical method in the CIN tissue,and the tissue of chronic cervicitis,cervical squamous cell carcinoma as control,to analyze the expression level of KLK7 in tissues of cervical precancerous lesions,the correlation of their expression level and CIN at different levels of analysis. Results This study showed that KLK7 widely exists in the CIN cytoplasm and nucleus in chronic cervicitis

  10. A refined model of the genomic basis for phenotypic variation in vertebrate hemostasis.

    Science.gov (United States)

    Ribeiro, Ângela M; Zepeda-Mendoza, M Lisandra; Bertelsen, Mads F; Kristensen, Annemarie T; Jarvis, Erich D; Gilbert, M Thomas P; da Fonseca, Rute R

    2015-06-30

    Hemostasis is a defense mechanism that enhances an organism's survival by minimizing blood loss upon vascular injury. In vertebrates, hemostasis has been evolving with the cardio-vascular and hemodynamic systems over the last 450 million years. Birds and mammals have very similar vascular and hemodynamic systems, thus the mechanism that blocks ruptures in the vasculature is expected to be the same. However, the speed of the process varies across vertebrates, and is particularly slow for birds. Understanding the differences in the hemostasis pathway between birds and mammals, and placing them in perspective to other vertebrates may provide clues to the genetic contribution to variation in blood clotting phenotype in vertebrates. We compiled genomic data corresponding to key elements involved in hemostasis across vertebrates to investigate its genetic basis and understand how it affects fitness. We found that: i) fewer genes are involved in hemostasis in birds compared to mammals; and ii) the largest differences concern platelet membrane receptors and components from the kallikrein-kinin system. We propose that lack of the cytoplasmic domain of the GPIb receptor subunit alpha could be a strong contributor to the prolonged bleeding phenotype in birds. Combined analysis of laboratory assessments of avian hemostasis with the first avian phylogeny based on genomic-scale data revealed that differences in hemostasis within birds are not explained by phylogenetic relationships, but more so by genetic variation underlying components of the hemostatic process, suggestive of natural selection. This work adds to our understanding of the evolution of hemostasis in vertebrates. The overlap with the inflammation, complement and renin-angiotensin (blood pressure regulation) pathways is a potential driver of rapid molecular evolution in the hemostasis network. Comparisons between avian species and mammals allowed us to hypothesize that the observed mammalian innovations might have

  11. systems

    Directory of Open Access Journals (Sweden)

    Alexander Leonessa

    2000-01-01

    Full Text Available A nonlinear robust control-system design framework predicated on a hierarchical switching controller architecture parameterized over a set of moving nominal system equilibria is developed. Specifically, using equilibria-dependent Lyapunov functions, a hierarchical nonlinear robust control strategy is developed that robustly stabilizes a given nonlinear system over a prescribed range of system uncertainty by robustly stabilizing a collection of nonlinear controlled uncertain subsystems. The robust switching nonlinear controller architecture is designed based on a generalized (lower semicontinuous Lyapunov function obtained by minimizing a potential function over a given switching set induced by the parameterized nominal system equilibria. The proposed framework robustly stabilizes a compact positively invariant set of a given nonlinear uncertain dynamical system with structured parametric uncertainty. Finally, the efficacy of the proposed approach is demonstrated on a jet engine propulsion control problem with uncertain pressure-flow map data.

  12. Rat plasma high-molecular-weight kininogen. A simple method for purification and its characterization.

    Science.gov (United States)

    Hayashi, I; Kato, H; Iwanaga, S; Oh-ishi, S

    1985-05-25

    High-molecular-weight kininogen has been isolated from rat plasma in three steps in a relatively high yield. The purified preparation gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence and presence of 2-mercaptoethanol, and the apparent Mr was estimated as 100,000. On incubation with rat plasma kallikrein, rat high Mr kininogen yielded a kinin-free protein consisting of a heavy chain (Mr = 64,000) and a light chain (Mr = 46,000), liberating bradykinin. The kinin-free protein was S-alkylated, and its heavy and light chains were separated by a zinc-chelating Sepharose 6B column. The amino acid compositions of rat high Mr kininogen and its heavy and light chains were very similar to those of bovine high Mr kininogen and its heavy and fragment 1.2-light chains, respectively. A high histidine content in the light chain of rat high Mr kininogen indicated the presence of a histidine-rich region in this protein as in bovine high Mr kininogen, although this region was not cleaved by rat plasma kallikrein. Rat high Mr kininogen corrected to normal values the prolonged activated partial thromboplastin time of Brown-Norway Katholiek rat plasma known to be deficient in high Mr kininogen and of Fitzgerald trait plasma. The kinin-free protein had the same correcting activity as intact high Mr kininogen. Rat high Mr kininogen also accelerated approximately 10-fold the surface-dependent activation of rat factor XII and prekallikrein, which was mediated with kaolin, amylose sulfate, and sulfatide. These results indicate that rat high Mr kininogen is quite similar to human and bovine high Mr kininogens in terms of biochemical and functional properties.

  13. Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

    Directory of Open Access Journals (Sweden)

    Charles E Bane

    Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

  14. Bothrops protease A, a unique highly glycosylated serine proteinase, is a potent, specific fibrinogenolytic agent.

    Science.gov (United States)

    Paes Leme, A F; Prezoto, B C; Yamashiro, E T; Bertholim, L; Tashima, A K; Klitzke, C F; Camargo, A C M; Serrano, S M T

    2008-08-01

    The hemostatic system is the major target of snake venom serine proteinases (SVSPs) that act on substrates of the coagulation, fibrinolytic and kallikrein-kinin systems. Bothrops protease A (BPA), the most glycosylated SVSP, is a non-coagulant, thermostable enzyme. A cDNA encoding BPA showed that the protein has a calculated molecular mass of 25 409 Da, implying that approximately 62% of its molecular mass as assessed by sodium dodecylsulfate polyacrylamide gel electrophoresis (67 kDa) is due to carbohydrate moieties. Here we show that BPA is a potent fibrinogenolytic agent in vitro, as it readily degraded human and rat fibrinogen at a very low enzyme concentration. Partially N-deglycosylated BPA (p-N-d-BPA) generated similar fibrinogen products, but with enhanced fibrinogenolytic activity. In vivo, injection of 0.75 nmoles of BPA in rats completely avoided thrombus formation induced by stasis in the vena cava, or by endothelium injury in the jugular vein. Moreover, it decreased the fibrinogen plasma level and prolonged the recalcification time. Cleavage of fibrinogen in human and rat plasma was observed with native BPA and p-N-d-BPA by electrophoresis followed by western blot using an anti-fibrinogen antibody. BPA did not cause unspecific degradation of plasma proteins and did not cleave isolated albumin, vitronectin and fibronectin at the same concentration used with fibrinogen. Serine proteinase inhibitors failed to inhibit BPA, probably due to steric hindrance caused by its huge carbohydrate moieties. To the best of our knowledge, this investigation underscores a new, thermostable, specific defibrinogenating agent that may have an application in the prevention of thrombus formation.

  15. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat

    Science.gov (United States)

    Khanmoradi, Mehrangiz; Ali Mard, Seyyed; Aboutaleb, Nahid; Nobakht, Malihe; Mahmoudian, Masoud

    2014-01-01

    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion injury in rats. Materials and Methods: Twenty four rats were randomly assigned to four groups; sham, RIR control, pre-and post-treatment with noscapine. To induce RIR injury, 20 days after right nephrectomy, animals underwent a midline laparotomy and the renal artery was clamped for 40 min to induce ischemia, and the clamp was then removed to allow reperfusion for 48 hr. Animals received noscapine or vehicle 1 hr before RIR or just prior to reperfusion. At the end of the experiment, animals were killed by cardiac exsanguination. Blood samples were collected to assess blood urea nitrogen (BUN) and creatinine. The kidneys were also removed for histopathlogical and western-blot analysis. Results: Noscapine treatment 1 hr before RIR or just prior to reperfusion protects the renal tissue structure as compared with the control. The expression levels of the studied inflammatory mediators, TNF-α and MCP-1in pretreated-, and treated-noscapine groups decreased as compared with the control group. The levels of BUN and creatinine in pre-, and post-treated noscapine groups were significantly lower than in control animals. Conclusion: Noscapine protects renal tissue structure and function against RIR through down-regulation of the inflammatory mediators. PMID:24904716

  16. Segmental Expression of the Bradykinin Type 2 Receptor in Rat Efferent Ducts and Epididymis and Its Role in the Regulation of Aquaporin 91

    Science.gov (United States)

    Belleannée, C.; Silva, N. Da; Shum, W.W.C.; Marsolais, M.; Laprade, R.; Brown, D.; Breton, S.

    2008-01-01

    Water and solute transport in the efferent ducts and epididymis are important for the establishment of the appropriate luminal environment for sperm maturation and storage. Aquaporin 9 (AQP9) is the main water channel in the epididymis, but its regulation is still poorly understood. Components of the kinin-kallikrein system (KKS), leading to the production of bradykinin (BK), are highly expressed in the lumen of the male reproductive tract. We report here that the epididymal luminal fluid contains a significant amount of BK (2 nM). RT-PCR performed on epididymal epithelial cells isolated by laser capture microdissection (LCM) showed abundant BK type 2 receptor (Bdkrb2) mRNA expression but no type 1 receptor (Bdkrb1). Double-immunofluorescence staining for BDKRB2 and the anion exchanger AE2 (a marker of efferent duct ciliated cells) or the V-ATPase E subunit, official symbol ATP6V1E1 (a marker of epididymal clear cells), showed that BDKRB2 is expressed in the apical pole of nonciliated cells (efferent ducts) and principal cells (epididymis). Triple labeling for BDKRB2, AQP9, and ATP6V1E1 showed that BDKRB2 and AQP9 colocalize in the apical stereocilia of principal cells in the cauda epididymidis. While uniform Bdkrb2 mRNA expression was detected in the efferent ducts and along the epididymal tubule, marked variations were detected at the protein level. BDKRB2 was highest in the efferent ducts and cauda epididymidis, intermediate in the distal initial segment, moderate in the corpus, and undetectable in the proximal initial segment and the caput. Functional assays on tubules isolated from the distal initial segments showed that BK significantly increased AQP9-dependent glycerol apical membrane permeability. This effect was inhibited by BAPTA-AM, demonstrating the participation of calcium in this process. This study, therefore, identifies BK as an important regulator of AQP9. PMID:18829705

  17. Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression

    Directory of Open Access Journals (Sweden)

    Shane D. Sykes

    2015-01-01

    Full Text Available The intrauterine renin angiotensin system (RAS is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2, angiotensin converting enzyme (ACE, angiotensin II type 1 receptor (AGTR1, and two proteases that can activate prorenin (kallikrein, KLK1, and cathepsin D, CTSD were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes and CTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes and CTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied. KLK1 was the most methylated gene and the proportion of hypermethylated KLK1 alleles was lower in placenta than decidua. The presence of intermediate methylated alleles of KLK1 in early gestation placenta and in amnion after labour suggests that KLK1 methylation is uniquely dynamic in these tissues.

  18. A history of late and very late stent thrombosis is not associated with increased activation of the contact system, a case control study

    Directory of Open Access Journals (Sweden)

    Brügger-Andersen Trygve

    2010-04-01

    Full Text Available Abstract Background The pathophysiological pathways resulting in Late Stent Thrombosis (LST remain uncertain. Findings from animal studies indicate a role of the intrinsic coagulation pathway in arterial thrombus formation, while clinical studies support an association with ischemic cardiovascular disease. It is currently unknown whether differences in the state of the contact system might contribute to the risk of LST or Very Late Stent Thrombosis (VLST. We assessed the relation between levels of several components involved in the contact system and a history of LST and VLST, termed (VLST in a cohort of 20 patients as compared to a matched control group treated with PCI. Methods and Results Activated factor XII (FXIIa, FXII zymogen (FXII, FXIIa-C1-esterase inhibitor (C1-inhibitor, Kallikrein-C1-inhibitor, FXIa-C1-inhibitor and FXIa-α1-antitrypsin (AT-inhibitor complexes were measured by Enzyme-linked immunosorbent assy (ELISA methodology. Cases and controls showed similar distributions in sex, age, baseline medications and stent type. Patients with a history of (VLST had a significantly greater stent burden and a higher number of previous myocardial infarctions than the control patients. There were no significant between-group differences in the plasma levels of the components of the contact system. Conclusion In a cohort of patients with a history of (VLST, we did not observe differences in the activation state of the intrinsic coagulation system as compared to patients with a history of percutaneous coronary intervention without stent thrombosis.

  19. systems

    Directory of Open Access Journals (Sweden)

    Patrick L. Brockett

    1978-01-01

    Full Text Available Suppose S={{Xnj,   j=1,2,…,kn}} is an infinitesimal system of random variables whose centered sums converge in law to a (necessarily infinitely divisible distribution with Levy representation determined by the triple (γ,σ2,M. If {Yj,   j=1,2,…} are independent indentically distributed random variables independent of S, then the system S′={{YjXnj,j=1,2,…,kn}} is obtained by randomizing the scale parameters in S according to the distribution of Y1. We give sufficient conditions on the distribution of Y in terms of an index of convergence of S, to insure that centered sums from S′ be convergent. If such sums converge to a distribution determined by (γ′,(σ′2,Λ, then the exact relationship between (γ,σ2,M and (γ′,(σ′2,Λ is established. Also investigated is when limit distributions from S and S′ are of the same type, and conditions insuring products of random variables belong to the domain of attraction of a stable law.

  20. system

    Science.gov (United States)

    Garcilazo, H.; Valcarce, A.; Vijande, J.

    2017-07-01

    Using local central Yukawa-type Malfliet-Tjon interactions reproducing the low-energy parameters and phase shifts of the nn system, and the latest updates of the nΛ and ΛΛ Nijmegen ESC08c potentials, we study the possible existence of a bound state. Our results indicate that the is unbound, being just above threshold. We discuss the role played by the 1 S 0 nn repulsive term of the Yukawa-type Malfliet-Tjon interaction. Supported by COFAA-IPN (México), Ministerio de Economía, Industria y Competitividad and EU FEDER (FPA2013-47443, FPA2015-69714-REDT, FPA2016-77177), Junta de Castilla y León (SA041U16) and Generalitat Valenciana PrometeoII/2014/066

  1. SYSTEM

    Directory of Open Access Journals (Sweden)

    K. Swarnalatha

    2013-01-01

    Full Text Available Risk analysis of urban aquatic systems due to heavy metals turns significant due to their peculiar properties viz. persis tence, non-degradab ility, toxicity, and accumulation. Akkulam Veli (AV, an urba n tropical lake in south India is subjected to various environmental stresses due to multiple waste discharge, sand mining, developmental activities, tour ism related activitie s etc. Hence, a comprehensive approach is adopted for risk assessment using modified degree of contamination factor, toxicity units based on numerical sediment quality guidelines (SQGs, and potentialecological risk indices. The study revealed the presence of toxic metals such as Cr, C d, Pb and As and the lake is rated under ‘low ecological risk’ category.

  2. The study of the relationships between social appearance anxiety, self-esteem and loneliness level among university studentsÜniversite öğrencilerinin sosyal görünüş kaygıları ile benlik saygıları ve yalnızlık düzeyleri arasındaki ilişkinin incelenmesi

    Directory of Open Access Journals (Sweden)

    Mehmet Kılıç

    2016-09-01

      Özet Bu araştırmanın temel amacı, üniversite öğrencilerinin sosyal görünüş kaygıları ile benlik saygıları ve yalnızlık düzeyleri arasındaki ilişkinin incelenmesidir. Tarama modelindeki bu araştırmaya 2013-2014 Eğitim Öğretim Yılında Karadeniz Teknik Üniversitesi İktisadi ve İdari Bilimler Fakültesi, Mühendislik Fakültesi, Eğitim Fakültesi, Sağlık Bilimleri Fakültesi, Hukuk Fakültesi, Fen Fakültesi, Edebiyat Fakültesi Tıp Fakültesi, İlahiyat Fakültesi, İletişim Fakültesi, Diş Hekimliği Fakültesi, Eczacılık Fakültesi, Mimarlık Fakültesi, Orman Fakültesi ve Turizm Otelcilik Meslek Yüksek Okulu’ nda öğrenim gören toplam  1386 (629 kadın, 756 erkek öğrenci katılmıştır. Araştırmada veri toplama araçları olarak; “Kişisel Bilgi Formu”,  “Sosyal Görünüş Kaygısı Ölçeği”, “Rosenberg Benlik Saygısı Ölçeği” ve “Ucla Yalnızlık Ölçeği” kullanılmıştır. Verilerin analizinde SSPS 16.0 paket programından yararlanılmıştır.Verilerin analizinde betimsel istatistiklerden; yüzde, frekans,aritmetik ortalama ve standart sapma teknikleri kullanılmıştır. Ayrıca araştırmada bağımsız gruplar için t-Testi, bağımsız gruplar için tek yönlü varyans analizi (ANOVAve farkın kaynağına bakmak amacıyla da Tukey testine başvurulmuştur. Bağımlı değişkenler arasındaki ilişkileri belirlemek için korelasyon ve regresyon analizleri yapılmıştır. Araştırmada üniversite öğrencilerinin, sosyal görünüş kaygısı ölçeğinden elde ettikleri ortalamalar açısından sosyal görünüş kaygı düzeylerinin düşük olduğu bulunmuştur. Bunun yanında öğrencilerin sosyal görünüş kaygısı puanlarıyla; cinsiyet, aile yapısı, hayatının önemli bir kısmını geçirdiği yer, kilosundan memnun olma durumu, boyundan memnun olma durumu ve marka giyinme değişkenleri açısından yapılan karşılaştırmalarda ise anlamlı bir farkl

  3. Analyzing the relationship between social networking addiction, interaction anxiousness and levels of loneliness of pre-service teachers Öğretmen adaylarının sosyal ağ bağımlılığı, etkileşim kaygısı ve yalnızlık düzeyi arasındaki ilişkinin incelenmesi

    Directory of Open Access Journals (Sweden)

    Hasan Özgür

    2013-11-01

    Full Text Available In this research, it was aimed to analyze the social networking addiction of pre-service teachers in terms of various variables and evaluate the relationship between social networking addiction and loneliness and interaction anxiousness. The research was designed according to the relational screening model. The study sample included 349 pre-service teachers studying at Trakya University Faculty of Education in 2012-2013 academic year fall term. The data were obtained using Facebook Addiction Scale, Interaction Anxiousness Scale, the UCLA-Loneliness Scale III and personal information form. In analysis of data, descriptive statistics, Mann Whitney U-Test, Kruskal-Wallis H and correlation tests were benefited. The research findings revealed that social networking addiction of pre-service teachers was at a low level, the relationship between interaction anxiousness and social networking addiction was high, and the relationship between the level of loneliness and social networking addiction was at a mid-level.  Moreover, in the research a statistically significant difference was obtained between the variables of social networking addiction and frequency of using social networking, gender and the level of grade they study.Bu araştırmada, öğretmen adaylarının sosyal ağ sitesi bağımlılık durumlarının çeşitli değişkenler açısından incelenmesi, sosyal ağ sitesi bağımlılığı ile yalnızlık ve etkileşim kaygısı arasındaki ilişkinin değerlendirilmesi amaçlanmıştır. Araştırma ilişkisel tarama modeline göre desenlenmiştir. Çalışma örneklemini, 2012-2013 öğretim yılı güz döneminde Trakya Üniversitesi Eğitim Fakültesi’nde öğrenim gören 349 öğretmen adayı oluşturmaktadır. Veriler, Facebook Bağımlılık Ölçeği, Etkileşim Kaygısı Ölçeği, UCLA-Yalnızlık Ölçeği III ve kişisel bilgiler formu ile elde edilmiştir. Verilerin analizinde betimsel istatistikler, Mann Whitney U, Kruskal

  4. Functional and structural diversification of the Anguimorpha lizard venom system.

    Science.gov (United States)

    Fry, Bryan G; Winter, Kelly; Norman, Janette A; Roelants, Kim; Nabuurs, Rob J A; van Osch, Matthias J P; Teeuwisse, Wouter M; van der Weerd, Louise; McNaughtan, Judith E; Kwok, Hang Fai; Scheib, Holger; Greisman, Laura; Kochva, Elazar; Miller, Laurence J; Gao, Fan; Karas, John; Scanlon, Denis; Lin, Feng; Kuruppu, Sanjaya; Shaw, Chris; Wong, Lily; Hodgson, Wayne C

    2010-11-01

    Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained

  5. Functional and Structural Diversification of the Anguimorpha Lizard Venom System*

    Science.gov (United States)

    Fry, Bryan G.; Winter, Kelly; Norman, Janette A.; Roelants, Kim; Nabuurs, Rob J. A.; van Osch, Matthias J. P.; Teeuwisse, Wouter M.; van der Weerd, Louise; Mcnaughtan, Judith E.; Kwok, Hang Fai; Scheib, Holger; Greisman, Laura; Kochva, Elazar; Miller, Laurence J.; Gao, Fan; Karas, John; Scanlon, Denis; Lin, Feng; Kuruppu, Sanjaya; Shaw, Chris; Wong, Lily; Hodgson, Wayne C.

    2010-01-01

    Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A2 toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained highlight

  6. 食源性血管紧张素抑制肽(ACEIP)的评价方法

    Institute of Scientific and Technical Information of China (English)

    郝记明; 章超桦; 郭顺堂

    2004-01-01

    原发性高血压是由多种因素引起的,其中包括遗传、饮食习惯、精神状态等。对于高血压发病机理,目前尚无一致的看法。研究表明血压正常与否,与肾素-血管紧张素系统(Renin-Angiotensin System,RAS)和激肽释放酶-激肽系统(Kallikrein-Kinin System,KKS)密切相关,而血管紧张素酶(Angiotensin I-Converting Enzyme,ACE)在上述两个系统中都起着重要作用。

  7. Interaction of Mimetic Analogs of Insect Kinin Neuropeptides with Arthropod Receptors

    Science.gov (United States)

    2010-01-01

    associated with the regulation of such diverse processes as hindgut contraction, diuresis and the release of digestive enzymes. In this chapter, the chemical...inhibition of diuresis in the housefly. Strategies for the modification of insect neuropeptide structures for the enhancement of the topical and oral...contraction, diuresis and the release of digestive enzymes. In this chapter, the chemical, conformational and stereochemical aspects of the activity

  8. Biostable Agonists that Match or Exceed Activity of Native Insect Kinins on Recombinant Arthropod GPCRs

    Science.gov (United States)

    2009-01-01

    Aib-1, 5.0 min.; K-Aib-2, 5.9 min.; K-Aib-3, 4.5 min.; K-Aib-4, 6.0 min.; K-Aib-5, 6.0 min.; K-Aib-6, 6.0 min. Amino acid analysis was car - ried out...bioactivity and resistance to peptidase hydrolysis. Biopolymers 88 (1), 76–82. 128 S. Taneja-Bageshwar et al. / General and Comparative Endocrinology 162 (2009) 122–128

  9. Global renal gene expression profiling analysis in B2-kinin receptor null mice: impact of diabetes.

    Directory of Open Access Journals (Sweden)

    Miran A Jaffa

    Full Text Available Diabetic nephropathy (DN, the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B(2-receptors (B(2R in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B(2R knockout (B(2R(-/- mice. Diabetes was induced with streptozotocin and plasma glucose levels and albumin excretion rate (AER were measured at predetermined times throughout the 23 week study period. Longitudinal analysis of AER indicated that diabetic B(2R(-/-D null mice had a significantly decreased AER levels compared to wild type B(2R(+/+D mice (P = 0.0005. Results from the global microarray study comparing gene expression profiles among four groups of mice respectively: (B(2R(+/+C, B(2R(+/+D, B(2R(-/-C and B(2R(-/-D highlighted the role of several altered pathological pathways in response to disruption of B(2R and to the diabetic state that included: endothelial injury, oxidative stress, insulin and lipid metabolism and inflammatory process with a marked alteration in the pro-apoptotic genes. The findings of the present study provide a global genomics view of biomarkers that highlight the mechanisms and putative pathways involved in DN.

  10. MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity

    DEFF Research Database (Denmark)

    Zhang, Yaping; Cardell, Lars-Olaf; Edvinsson, Lars;

    2013-01-01

    Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the deve...

  11. 20 Years On: Is It Time to Redefine the Systemic Inflammatory Response to Cardiothoracic Surgery?

    Science.gov (United States)

    Landis, R Clive

    2015-03-01

    The "systemic inflammatory response" has never been defined from a cardiothoracic surgery perspective, but borrowed its definition from the critical care field at a landmark 1992 definition conference on sepsis. It is unclear why the diagnostic criteria for the Systemic Inflammatory Response Syndrome (SIRS) were adopted in isolation, ignoring other potentially more useful definitions for Severe Septic Shock or Secondary Multiple Organ Dysfunction Syndrome. The 1992 SIRS definition for sepsis has since been updated at a conference in 2001 advocating PIRO (Predisposition, Infection, host Response, Organ dysfunction) as a hypothetical model to better link sepsis with clinical outcome. PIRO is readily adaptable to cardiothoracic surgery and provides the precedent and road map for how to update a definition. The need is obvious since the current definition of SIRS is widely disregarded in heart surgery: a dwindling proportion (14%) of articles on the systemic inflammatory response even mention SIRS and 0% monitored SIRS criteria in the past decade in an evidence-based review of anti-inflammatory interventions. The name "inflammatory response" is also problematic; it is too narrow and might be replaced with host response (the R in PIRO) to better convey the wide spectrum of host defensive pathways activated during heart surgery (i.e., complement, coagulation, fibrinolysis, kinins, cytokines, proteases, hemolysis, oxidative stiess). A variant on PIRO could allow these elements of the host Response (R) to be anchored within the context of Premorbid conditions (P) and the inevitable Insult (I) from surgery, to better link risk exposures to Organ dysfunction (O) in heart surgery. The precedent of PIRO suggests the following steps will be required to redefine the systemic inflammatory response: 1) buy-in from the leading societies for cardiothoracic surgery, anesthesia, and perfusion on the need for a re-definition conference, 2) assigning relative risk scores to different

  12. Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Liu, Y H; Yang, X P; Sharov, V G; Sigmon, D H; Sabbath, H N; Carretero, O A

    1996-01-01

    After transient episodes of ischemia, benefits of thrombolytic or angioplastic therapy may be limited by reperfusion injury. Angiotensin-converting enzyme inhibitors protect the heart against ischemia/reperfusion injury, an effect mediated by kinins. We examined whether the protective effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of prostaglandin and/or nitric oxide release. The left anterior descending coronary artery of Lewis inbred rats was occluded for 30 minutes, followed by 120 minutes of reperfusion. Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan. We tested whether pretreatment with the kinin receptor antagonist Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor indomethacin blocked the effect of ramiprilat on infarct size and reperfusion arrhythmias. In controls, infarct size as a percentage of the area at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (P < .001), but losartan had little effect (74 +/- 6%, P = NS). Pretreatment with Hoe 140, NG-nitro-L-arginine methyl ester, or indomethacin abolished the beneficial effect of ramiprilat. Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 minutes of ischemia had significantly smaller infarct size as a percentage of the area at risk, whereas in the 150-minute ischemia group it was significantly larger. This suggests that reperfusion caused a significant part of the myocardial injury, but it also suggests that compared with prolonged ischemia, reperfusion salvaged some of the myocardium. Ventricular arrhythmias mirrored the changes in infarct size. Thus, angiotensin-converting enzyme inhibitors protect the myocardium against ischemia/reperfusion injury and arrhythmias; these beneficial effects are mediated primarily by a kinin

  13. Biochemical aspects on adverse reactions to contrast media. Changes of kininogen levels in dog plasma after intravenous injections of iohexol, iopamidol, and iothalamate.

    Science.gov (United States)

    Tanaka, T; Katayama, H; Shirakata, A; Takahasi, H

    1988-09-01

    The adverse reactions to contrast media have been investigated by several authors but the exact mechanisms have not yet been established. To study whether kinin-releasing systems are involved in these adverse reactions, we determined total plasma kininogen levels at intervals up to 30 minutes after the intravenous injections of contrast media in dogs. Injections of iohexol, iopamidol, and iothalamate decreased total plasma kininogen levels. This effect increased with increasing dose of the media and suggests that they activated the kinin-releasing systems in the plasma.

  14. Developing a Novel Therapeutic Strategy Targeting Kallikrein-4 to Inhibit Prostate Cancer Growth and Metastasis

    Science.gov (United States)

    2015-08-01

    using Lipofectamine reagent (Life Technologies), and selection for transfectants began 72 hours post-transfection with G418 antibiotic at 1mg/mL...Medical Center, USA) were maintained in RPMI media containing 5% fetal bovine serum (Gibco, Life Technologies). All cell lines were incubated at 37°C in...Technologies, Mulgrave, Vic, Aust) containing 10% fetal bovine serum (FBS; Moregate, Brisbane, Aust). The targeted and non- targeted polymers were made to 5

  15. Kallikrein 4 and matrix metalloproteinase-20 immunoexpression in malignant, benign and infiltrative odontogenic tumors

    Directory of Open Access Journals (Sweden)

    Marcelo Macedo Crivelini

    2016-01-01

    Conclusions: Data showed that KLK4 and MMP20 enzymes may not be crucial to tumoral infiltrative capacity, especially in malignant tumors, considering the diversity and peculiarity of these lesions. The significant immunoexpression in benign lesions, remarkably in AOT, is likely associated with differentiated tumor cells that can produce and degrade enamel matrix-like substances. This would be expected since the histogenesis of odontogenic tumors commonly comes from epithelium that recently performed a secretory activity in tooth formation.

  16. Biological Function of Plasma Kallikrein in Mammary Gland Stromal Development and Tumor Metastasis

    Science.gov (United States)

    2008-03-01

    L.A. Dent. 2003. Interleukin-5 transgene expression and eosinophilia are associated with retarded mammary gland development in mice. Biology of...and L.A. Dent. 2003. Interleukin-5 transgene expression and eosinophilia are associated with retarded mammary gland development in mice. Biology of

  17. Processing of epidermal growth factor in the rat submandibular gland by Kallikrein-like enzymes

    DEFF Research Database (Denmark)

    Jørgensen, P E; Nexø, Ebba; Poulsen, Steen Seier;

    1994-01-01

    , rK2, rK7, rK9 or rK10, can process the rat EGF precursor. Molecular weight forms of EGF, that were N- or C-terminally extended compared to submandibular gland EGF were obtained from rat urine. These extended forms of EGF were incubated with each of the enzymes for 24 h at 37 degrees C. Two enzymes......-terminally extended EGF. Neither rK2, nor rK9 cleaved the extended forms of EGF. In previous immunohistochemical studies rK1, rK7 and rK10 have all been demonstrated in the EGF containing cells of the rat submandibular gland. EGF and rK1 are also synthesized in the rat kidney but the present study demonstrated...

  18. Proteins of the Hageman Factor System in an Inflammatory Reaction in the Acute Period of Severe Brain Injury

    Directory of Open Access Journals (Sweden)

    T. I. Borshchikova

    2010-01-01

    Full Text Available Objective: to study the time course of changes and an association of contact factors and their inhibitors with the global values of hemocoagulation, fibrinolysis, and inflammatory reactants in acute severe brain injury (SBI in order to deepen notions of Hageman factor system functioning. Subjects and methods. One hundred and thirteen patients with SBI were examined on 1 to 21 days of injury. The level of unconsciousness averaged a Glasgow coma score of 6.8±0.25. A control group included 23 healthy individuals. The investigators determined the activity of contact factors (prekallikrein, high-molecular-weight kininogen, factors XII, XI and their inhibitors (total activity of the protein C system, the activity and quantity of antithrombin III, C1 esterase inhibitor, a^antitrypsin, fl^-antiplasmin, fl^-macroglobulin, hemostatic parameters (blood fibrinolytic activity by an euglobulin test; factor XII-kallikrein-dependent fibrinolysis, treptokinase induced fibrinolysis by calculating the plasminogen reserve index, activated partial thromboplastin time, fibrinogen, D-dimer, and soluble fibrin monomer complexes, and inflammatory reactants (C-reactive protein, IL10, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNF-a, and IFN-y. Results. The acute period of SBI was marked by significant deficiency and imbalance of contact factors and their physiological inhibitors. In SBI, prekallikrein rather than factor XII plays a central role in the function of the contact factor system due to inflammatory inhibition of Hageman factor synthesis, which disturbs its key role in the reactions of contact activation of homeostatic proteolytic systems. Out of the considered systems, the activation of which is associated with contact factors, the function of the internal mechanism of fibrinolysis is largely changed; at the same time the internal hemocoagulation activation pathway remains virtually intact. When an inflammatory reaction develops after SBI, normal Hageman factor

  19. Trauma Induced Pain and Wound Management in Emergency Environment by Low Energy Photonic Therapy

    Science.gov (United States)

    2004-09-01

    joint capsule or fascial compartments by blood or tissue fluid transudate • Tissue damage followed by activation of kinin and prostaglandin systems...the following groups: Group #1 (17 pts) received Chiropractic Manipulative Therapy (CMP); Group #2 (18 pts) received CMT plus Exercise Therapy (Ex

  20. Blood hibernation: a novel strategy to inhibit systemic inflammation and coagulation induced by cardiopulmonary bypass

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jing; WU Xiao-dong; LIN Ke; Raphael C. Lui; AN Qi; TAO Kai-yu; DU Lei; LIU Jin

    2010-01-01

    Background Inflammation and coagulation are two intimately cross-linked defense mechanisms of most, if not all organisms to injuries. During cardiopulmonary bypass (CPB), these two process-is are activated and interact with each other through several common pathways, which may result in subsequent organ dysfunction. In the present study, we hypothesized that the addition of nitric oxide, prostaglandin E1 (PGE1), and aprotinin to the systemic circulation, hereby referred to as blood hibernation, would attenuate the inflammation and coagulation induced by CPB. Methods Thirty adult mongrel dogs were equally divided into five groups, anesthetized and placed on hypothermic CPB (32 C). Each group received respectively the following treatments: (1) inhalation of 40 ppm nitric oxide; (2) intravenous infusion of 20 ng·kg-1·min-1 of PGE1; (3) 80 000 kallikrein inhibitor units (KIU)/kg of aprotinin; (4) the combination of all three agents (blood hibernation group); and (5) no treatment (control group) during CPB. Activation of leukocyte, platelet, endothelial cell, and formation of thrombin were assessed after CPB.Results As compared with the other four groups, leukocyte counts were higher, while plasma elastase, interleukin-8, CD11b mRNA expression, myeloperoxidase activities and lung tissue leukocyte counts were lower in the blood hibernation group (P<0.05 versus other four groups after CPB). Plasma prothrombin fragment (PTF)1+2, and platelet activation factors were lower, while platelet counts were higher in the blood hibernation group (P<0.05 versus other four groups at 6 and 12 hours after CPB). Electron microscopy showed endothelial pseudopods protrusion, with cell adherence in all four groups except the blood hibernation group where endothelial cells remained intact.Conclusion Blood hibernation, effected by the addition of nitric oxide, PGE1 and aprotinin to the circulating blood during extra-corporeal circulation, was observed to attenuate the inflammation and

  1. Comparison of insect kinin analogs with cis-peptide bond, type VI-turn motifs identifies optimal stereochemistry for interaction with a recombinant arthropod kinin receptor from the Southern cattle tick, Boophilus microplus

    Science.gov (United States)

    The multifunctional ‘insect kinins’ share the evolutionarily conserved C-terminal pentapeptide motif Phe-X1-X2-Trp-Gly-NH2, where X1 = His, Asn, Ser, or Tyr and X2 = Ser, Pro, or Ala; and are associated with the regulation of diuresis in a variety of species of insects. We previously reported the f...

  2. Antifeedant Activity and High Mortality in the Pea Aphid Acyrthosiphon pisum (Hemiptera: Aphidae) Induced by Biostable Insect Kinin Analogs

    Science.gov (United States)

    2010-01-01

    and whiteflies . But intensive use of imidacloprid has stimulated outbreaks of resistance and cross resistance in many cases [7]. In the group of...Alford DV. Pest and disease management handbook. Oxford, UK: British Crop Protection Enterprises, Blackwell Science Ltd; 2000. [2] Cheng RP, Gellman SH

  3. De werking van de hydro- en acetylverbindingen van kinidine en kinine op het hart van Rana esculenta

    NARCIS (Netherlands)

    Sibie, Johan Dirk

    1942-01-01

    In hoofdstuk I werd een inleiding gegeven betreffende de geschiedenis van de kina en van het begin der kinacultuur op Java, de chemie der kinaälkaloïden en enkele aspecten der pharmacologische werking van de kinaderivaten. ... Zie: Samenvatting

  4. Safety pharmacology, toxicology and pharmacokinetic assesment of human Gc globulin (vitamin d binding protein)

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Jørgensen, Charlotte Sværke; Santoni Rugiu, Eric

    2010-01-01

    of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day...

  5. Mechanisms involved in the nociception triggered by the venom of the armed spider Phoneutria nigriventer.

    Directory of Open Access Journals (Sweden)

    Camila Gewehr

    Full Text Available BACKGROUND: The frequency of accidental spider bites in Brazil is growing, and poisoning due to bites from the spider genus Phoneutria nigriventer is the second most frequent source of such accidents. Intense local pain is the major symptom reported after bites of P. nigriventer, although the mechanisms involved are still poorly understood. Therefore, the aim of this study was to identify the mechanisms involved in nociception triggered by the venom of Phoneutria nigriventer (PNV. METHODOLOGY/PRINCIPAL FINDINGS: Twenty microliters of PNV or PBS was injected into the mouse paw (intraplantar, i.pl.. The time spent licking the injected paw was considered indicative of the level of nociception. I.pl. injection of PNV produced spontaneous nociception, which was reduced by arachnid antivenin (ArAv, local anaesthetics, opioids, acetaminophen and dipyrone, but not indomethacin. Boiling or dialysing the venom reduced the nociception induced by the venom. PNV-induced nociception is not dependent on glutamate or histamine receptors or on mast cell degranulation, but it is mediated by the stimulation of sensory fibres that contain serotonin 4 (5-HT4 and vanilloid receptors (TRPV1. We detected a kallikrein-like kinin-generating enzyme activity in tissue treated with PNV, which also contributes to nociception. Inhibition of enzymatic activity or administration of a receptor antagonist for kinin B2 was able to inhibit the nociception induced by PNV. PNV nociception was also reduced by the blockade of tetrodotoxin-sensitive Na(+ channels, acid-sensitive ion channels (ASIC and TRPV1 receptors. CONCLUSION/SIGNIFICANCE: Results suggest that both low- and high-molecular-weight toxins of PNV produce spontaneous nociception through direct or indirect action of kinin B2, TRPV1, 5-HT4 or ASIC receptors and voltage-dependent sodium channels present in sensory neurons but not in mast cells. Understanding the mechanisms involved in nociception caused by PNV are of

  6. System Budgets

    DEFF Research Database (Denmark)

    Jeppesen, Palle

    1996-01-01

    The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers.......The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers....

  7. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood sample...

  8. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III.

    Science.gov (United States)

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M; Drouet, Christian; Braley, Hal; Nolte, Marc W; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-08-03

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12-/- mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes.

  9. An overview of novel therapies for acute hereditary angioedema.

    Science.gov (United States)

    Firszt, Rafael; Frank, Michael M

    2010-12-01

    Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by nonpitting edema of external or mucosal body surfaces. Patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can at times lead to asphyxiation. The disease is caused by a mutation in the gene encoding the complement C1-inhibitor protein, which leads to unregulated production of bradykinin. Long-term therapy has depended on the use of attenuated androgens or plasmin inhibitors but in the US there was, until recently, no specific therapy for acute attacks. As well, many patients with hereditary angioedema in the US were either not adequately controlled on previously available therapies or required doses of medications that exposed them to the risk of serious adverse effects. Five companies have completed or are currently conducting phase III clinical trials in the development of specific therapies to terminate acute attacks or to be used as prophylaxis. These products are based on either replacement therapy with purified plasma-derived or recombinant C1-inhibitor, or inhibition of the kinin-generating pathways with a recombinant plasma kallikrein inhibitor or bradykinin type 2 receptor antagonist. Published studies thus far suggest that all of these products are likely to be effective. These new therapies will likely lead to a totally new approach in treating hereditary angioedema.

  10. System Identification

    NARCIS (Netherlands)

    Keesman, K.J.

    2011-01-01

    Summary System Identification Introduction.- Part I: Data-based Identification.- System Response Methods.- Frequency Response Methods.- Correlation Methods.- Part II: Time-invariant Systems Identification.- Static Systems Identification.- Dynamic Systems Identification.- Part III: Time-varying

  11. Cleavage of kininogen and subsequent bradykinin release by the complement component: mannose-binding lectin-associated serine protease (MASP-1.

    Directory of Open Access Journals (Sweden)

    József Dobó

    Full Text Available Bradykinin (BK, generated from high-molecular-weight kininogen (HK is the major mediator of swelling attacks in hereditary angioedema (HAE, a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×10(2 and 2.7×10(2 M(-1 s(-1, respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients.

  12. Gradient systems and mechanical systems

    Institute of Scientific and Technical Information of China (English)

    Fengxiang Mei; Huibin Wu

    2016-01-01

    All types of gradient systems and their properties are discussed. Two problems connected with gradient sys-tems and mechanical systems are studied. One is the direct problem of transforming a mechanical system into a gradi-ent system, and the other is the inverse problem, which is transforming a gradient system into a mechanical system.

  13. Carbamazepine inhibits angiotensin I-converting enzyme, linking it to the pathogenesis of temporal lobe epilepsy

    Science.gov (United States)

    Almeida, S S; Naffah-Mazzacoratti, M G; Guimarães, P B; Wasinski, F; Pereira, F E G; Canzian, M; Centeno, R S; Carrete, H; Yacubian, E M; Carmona, A K; Vieira, R F F; Nakaie, C R; Sabatini, R A; Perosa, S R; Bacurau, R F P; Gouveia, T L F; Gallo, G; Würtele, M; Cavalheiro, E A; Silva, J A; Pesquero, J B; Araujo, R C

    2012-01-01

    We find that a common mutation that increases angiotensin I-converting enzyme activity occurs with higher frequency in male patients suffering from refractory temporal lobe epilepsy. However, in their brains, the activity of the enzyme is downregulated. As an explanation, we surprisingly find that carbamazepine, commonly used to treat epilepsy, is an inhibitor of the enzyme, thus providing a direct link between epilepsy and the renin–angiotensin and kallikrein–kinin systems. PMID:22832858

  14. Thermal systems; Systemes thermiques

    Energy Technology Data Exchange (ETDEWEB)

    Lalot, S. [Valenciennes Univ. et du Hainaut Cambresis, LME, 59 (France); Lecoeuche, S. [Ecole des Mines de Douai, Dept. GIP, 59 - Douai (France)]|[Lille Univ. des Sciences et Technologies, 59 - Villeneuve d' Ascq (France); Ahmad, M.; Sallee, H.; Quenard, D. [CSTB, 38 - Saint Martin d' Heres (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Gascoin, N.; Gillard, P.; Bernard, S. [Laboratoire d' Energetique, Explosion, Structure, 18 - Bourges (France); Gascoin, N.; Toure, Y. [Laboratoire Vision et Robotique, 18 - Bourges (France); Daniau, E.; Bouchez, M. [MBDA, 18 - Bourges (France); Dobrovicescu, A.; Stanciu, D. [Bucarest Univ. Polytechnique, Faculte de Genie Mecanique (Romania); Stoian, M. [Reims Univ. Champagne Ardenne, Faculte des Sciences, UTAP/LTM, 51 (France); Bruch, A.; Fourmigue, J.F.; Colasson, S. [CEA Grenoble, Lab. Greth, 38 (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Voicu, I.; Mare, T.; Miriel, J. [Institut National des Sciences Appliquees (INSA), LGCGM, IUT, 35 - Rennes (France); Galanis, N. [Sherbrooke Univ., Genie Mecanique, QC (Canada); Nemer, M.; Clodic, D. [Ecole des Mines de Paris, Centre Energetique et Procedes, 75 (France); Lasbet, Y.; Auvity, B.; Castelain, C.; Peerhossaini, H. [Nantes Univ., Ecole Polytechnique, Lab. de Thermocinetiquede Nantes, UMR-CNRS 6607, 44 (France)

    2005-07-01

    This session about thermal systems gathers 26 articles dealing with: neural model of a compact heat exchanger; experimental study and numerical simulation of the thermal behaviour of test-cells with walls made of a combination of phase change materials and super-insulating materials; hydraulic and thermal modeling of a supercritical fluid with pyrolysis inside a heated channel: pre-dimensioning of an experimental study; energy analysis of the heat recovery devices of a cryogenic system; numerical simulation of the thermo-hydraulic behaviour of a supercritical CO{sub 2} flow inside a vertical tube; mixed convection inside dual-tube exchangers; development of a nodal approach with homogenization for the simulation of the brazing cycle of a heat exchanger; chaotic exchanger for the cooling of low temperature fuel cells; structural optimization of the internal fins of a cylindrical generator; a new experimental approach for the study of the local boiling inside the channels of exchangers with plates and fins; experimental study of the flow regimes of boiling hydrocarbons on a bundle of staggered tubes; energy study of heat recovery exchangers used in Claude-type refrigerating systems; general model of Carnot engine submitted to various operating constraints; the free pistons Stirling cogeneration system; natural gas supplied cogeneration system with polymer membrane fuel cell; influence of the CRN coating on the heat flux inside the tool during the wood unrolling process; transport and mixture of a passive scalar injected inside the wake of a Ahmed body; control of a laser welding-brazing process by infrared thermography; 2D self-adaptative method for contours detection: application to the images of an aniso-thermal jet; exergy and exergy-economical study of an 'Ericsson' engine-based micro-cogeneration system; simplified air-conditioning of telephone switching equipments; parametric study of the 'low-energy' individual dwelling; brief synthesis of

  15. SwissProt search result: AK061101 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061101 006-207-A12 (P07647) Submandibular glandular kallikrein-9 precursor (EC 3....4.21.35) (Tissue kallikrein) (S3 kallikrein) (Submandibular enzymatic vasoconstrictor) (SEV) (KLK-S3) [Contains: Submandibular glandu...lar kallikrein-9 light chain; Submandibular glandu KLK9_RAT 2e-18 ...

  16. SwissProt search result: AK112005 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112005 006-202-F10 (P07647) Submandibular glandular kallikrein-9 precursor (EC 3....4.21.35) (Tissue kallikrein) (S3 kallikrein) (Submandibular enzymatic vasoconstrictor) (SEV) (KLK-S3) [Contains: Submandibular glandu...lar kallikrein-9 light chain; Submandibular glandu KLK9_RAT 4e-11 ...

  17. SwissProt search result: AK109059 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109059 002-154-F02 (P07647) Submandibular glandular kallikrein-9 precursor (EC 3....4.21.35) (Tissue kallikrein) (S3 kallikrein) (Submandibular enzymatic vasoconstrictor) (SEV) (KLK-S3) [Contains: Submandibular glandu...lar kallikrein-9 light chain; Submandibular glandu KLK9_RAT 2e-17 ...

  18. SwissProt search result: AK112119 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112119 006-303-H09 (P07647) Submandibular glandular kallikrein-9 precursor (EC 3....4.21.35) (Tissue kallikrein) (S3 kallikrein) (Submandibular enzymatic vasoconstrictor) (SEV) (KLK-S3) [Contains: Submandibular glandu...lar kallikrein-9 light chain; Submandibular glandu KLK9_RAT 3e-11 ...

  19. Data Systems vs. Information Systems

    OpenAIRE

    Amatayakul, Margret K.

    1982-01-01

    This paper examines the current status of “hospital information systems” with respect to the distinction between data systems and information systems. It is proposed that the systems currently existing are incomplete data dystems resulting in ineffective information systems.

  20. Data Systems vs. Information Systems

    OpenAIRE

    Amatayakul, Margret K.

    1982-01-01

    This paper examines the current status of “hospital information systems” with respect to the distinction between data systems and information systems. It is proposed that the systems currently existing are incomplete data dystems resulting in ineffective information systems.

  1. C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles.

    Science.gov (United States)

    Mossberg, Maria; Ståhl, Anne-Lie; Kahn, Robin; Kristoffersson, Ann-Charlotte; Tati, Ramesh; Heijl, Caroline; Segelmark, Mårten; Leeb-Lundberg, L M Fredrik; Karpman, Diana

    2017-08-01

    The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (Pmicrovesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor-depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation. Copyright © 2017 by the American Society of Nephrology.

  2. Multibody Systems

    DEFF Research Database (Denmark)

    Wagner, Falko Jens

    1999-01-01

    Multibody Systems is one area, in which methods for solving DAEs are of special interst. This chapter is about multibody systems, why they result in DAE systems and what kind of problems that can arise when dealing with multibody systems and formulating their corresponding DAE system....

  3. Lymph system

    Science.gov (United States)

    Lymphatic system ... neck, under the arms, and groin. The lymph system includes the: Tonsils Adenoids Spleen Thymus ... JE, Flynn JA, Solomon BS, Stewart RW. Lymphatic system. In: Ball JW, Dains JE, Flynn JA, Solomon ...

  4. Systems effectiveness

    CERN Document Server

    Habayeb, A R

    1987-01-01

    Highlights three principal applications of system effectiveness: hardware system evaluation, organizational development and evaluation, and conflict analysis. The text emphasizes the commonality of the system effectiveness discipline. The first part of the work presents a framework for system effectiveness, partitioning and hierarchy of hardware systems. The second part covers the structure, hierarchy, states, functions and activities of organizations. Contains an extended Appendix on mathematical concepts and also several project suggestions.

  5. Bitcoin System

    Directory of Open Access Journals (Sweden)

    Jan Lánský

    2017-06-01

    Full Text Available Cryptocurrency systems are purely digital and decentralized systems that use cryptographic principles to confirm transactions. Bitcoin is the first and also the most widespread cryptocurrency. The aim of this article is to introduce Bitcoin system using a language understandable also to readers without computer science education. This article captures the Bitcoin system from three perspectives: internal structure, network and users. Emphasis is placed on brief and clear definitions (system components and their mutual relationships. A new system view of the stated terms constitutes author’s own contribution.

  6. Intelligent Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — The autonomous systems (AS) project, led by NASA Ames, is developing software for system operation automation. AS technology will help astronauts make more decisions...

  7. Systems Engineering

    Science.gov (United States)

    Pellerano, Fernando

    2015-01-01

    This short course provides information on what systems engineering is and how the systems engineer guides requirements, interfaces with the discipline leads, and resolves technical issues. There are many system-wide issues that either impact or are impacted by the thermal subsystem. This course will introduce these issues and illustrate them with real life examples.

  8. Retrofitting Systems

    DEFF Research Database (Denmark)

    Rose, Jørgen

    1997-01-01

    This report gives an overview of the different retrofitting possibilities that are available today. The report looks at both external and internal systems for external wall constructions, roof constructions, floor constructions and foundations. All systems are described in detail in respect to use...... and methods, and the efficiency of the different systems are discussed....

  9. Operating systems

    CERN Document Server

    Tsichritzis, Dionysios C; Rheinboldt, Werner

    1974-01-01

    Operating Systems deals with the fundamental concepts and principles that govern the behavior of operating systems. Many issues regarding the structure of operating systems, including the problems of managing processes, processors, and memory, are examined. Various aspects of operating systems are also discussed, from input-output and files to security, protection, reliability, design methods, performance evaluation, and implementation methods.Comprised of 10 chapters, this volume begins with an overview of what constitutes an operating system, followed by a discussion on the definition and pr

  10. Cryogenic Systems

    Science.gov (United States)

    Hosoyama, Kenji

    2002-02-01

    In this lecture we discuss the principle of method of cooling to a very low temperature, i.e. cryogenic. The "gas molecular model" will be introduced to explain the mechanism cooling by the expansion engine and the Joule-Thomson expansion valve. These two expansion processes are normally used in helium refrigeration systems to cool the process gas to cryogenic temperature. The reverse Carnot cycle will be discussed in detail as an ideal refrigeration cycle. First the fundamental process of liquefaction and refrigeration cycles will be discussed, and then the practical helium refrigeration system. The process flow of the system and the key components; -compressor, expander, and heat exchanger- will be discussed. As an example of an actual refrigeration system, we will use the cryogenic system for the KEKB superconducting RF cavity. We will also discuss the liquid helium distribution system, which is very important, especially for the cryogenic systems used in accelerator applications. 1 Principles of Cooling and Fundamental Cooling Cycle 2 Expansion engine, Joule-Thomson expansion, kinetic molecular theory, and enthalpy 3 Liquefaction Systems 4 Refrigeration Systems 5 Practical helium liquefier/refrigeration system 6 Cryogenic System for TRISTAN Superconducting RF Cavity

  11. Expert System

    DEFF Research Database (Denmark)

    Hildebrandt, Thomas Troels; Cattani, Gian Luca

    2016-01-01

    An expert system is a computer system for inferring knowledge from a knowledge base, typically by using a set of inference rules. When the concept of expert systems was introduced at Stanford University in the early 1970s, the knowledge base was an unstructured set of facts. Today the knowledge...... base of expert systems is often given in terms of an ontology, extracted and built from various data sources by employing natural language-processing and statistics. To emphasize such capabilities, the term “expert” is now often replaced by “cognitive,” “knowledge,” “knowledge-based,” or “intelligent......” system. With very few exceptions, general-purpose expert systems have failed to emerge so far. However, expert systems are applied in specialized domains, particularly in healthcare. The increasing availability of large quantities of data to organizations today provides a valuable opportunity...

  12. Recommender systems

    CERN Document Server

    Kembellec, Gérald; Saleh, Imad

    2014-01-01

    Acclaimed by various content platforms (books, music, movies) and auction sites online, recommendation systems are key elements of digital strategies. If development was originally intended for the performance of information systems, the issues are now massively moved on logical optimization of the customer relationship, with the main objective to maximize potential sales. On the transdisciplinary approach, engines and recommender systems brings together contributions linking information science and communications, marketing, sociology, mathematics and computing. It deals with the understan

  13. Material Systems

    DEFF Research Database (Denmark)

    Jensen, Mads Brath; Mortensen, Henrik Rubæk; Mullins, Michael;

    2009-01-01

    This paper describes and reflects upon the results of an investigative project which explores the setting up of a material system - a parametric and generative assembly consisting of and taking into consideration material properties, manufacturing constraints and geometric behavior. The project...... approaches the subject through the construction of a logic-driven system aiming to explore the possibilities of a material system that fulfills spatial, structural and performative requirements concurrently and how these are negotiated in situations where they might be conflicting....

  14. Material Systems

    DEFF Research Database (Denmark)

    Jensen, Mads Brath; Mortensen, Henrik Rubæk; Mullins, Michael

    2009-01-01

    This paper describes and reflects upon the results of an investigative project which explores the setting up of a material system - a parametric and generative assembly consisting of and taking into consideration material properties, manufacturing constraints and geometric behavior. The project...... approaches the subject through the construction of a logic-driven system aiming to explore the possibilities of a material system that fulfills spatial, structural and performative requirements concurrently and how these are negotiated in situations where they might be conflicting....

  15. Intelligent systems

    CERN Document Server

    Irwin, J David

    2011-01-01

    Technology has now progressed to the point that intelligent systems are replacing humans in the decision making processes as well as aiding in the solution of very complex problems. In many cases intelligent systems are already outperforming human activities. Artificial neural networks are not only capable of learning how to classify patterns, such images or sequence of events, but they can also effectively model complex nonlinear systems. Their ability to classify sequences of events is probably more popular in industrial applications where there is an inherent need to model nonlinear system

  16. Energetic Systems

    Data.gov (United States)

    Federal Laboratory Consortium — The Energetic Systems Division provides full-spectrum energetic engineering services (project management, design, analysis, production support, in-service support,...

  17. Systemic darwinism.

    Science.gov (United States)

    Winther, Rasmus Grønfeldt

    2008-08-19

    Darwin's 19th century evolutionary theory of descent with modification through natural selection opened up a multidimensional and integrative conceptual space for biology. We explore three dimensions of this space: explanatory pattern, levels of selection, and degree of difference among units of the same type. Each dimension is defined by a respective pair of poles: law and narrative explanation, organismic and hierarchical selection, and variational and essentialist thinking. As a consequence of conceptual debates in the 20th century biological sciences, the poles of each pair came to be seen as mutually exclusive opposites. A significant amount of 21st century research focuses on systems (e.g., genomic, cellular, organismic, and ecological/global). Systemic Darwinism is emerging in this context. It follows a "compositional paradigm" according to which complex systems and their hierarchical networks of parts are the focus of biological investigation. Through the investigation of systems, Systemic Darwinism promises to reintegrate each dimension of Darwin's original logical space. Moreover, this ideally and potentially unified theory of biological ontology coordinates and integrates a plurality of mathematical biological theories (e.g., self-organization/structure, cladistics/history, and evolutionary genetics/function). Integrative Systemic Darwinism requires communal articulation from a plurality of perspectives. Although it is more general than these, it draws on previous advances in Systems Theory, Systems Biology, and Hierarchy Theory. Systemic Darwinism would greatly further bioengineering research and would provide a significantly deeper and more critical understanding of biological reality.

  18. cardiovascular system

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    6.1 Cardiac arrhythmias 2006037 Electroanatomical systems guided circumferential pulmonary veins ablation for atrial fibrillation: initial experience from comparison between the EnSite -NavX and CARTO system LIU Xu(刘旭 ), et al. Dept Cardiol, Shanghai Chest Hosp, Shanghai, 200030, China. Chin J Cardiol 2005; 33 (22): 975 -978.

  19. Linear Systems.

    Science.gov (United States)

    The report documents a series of seminars at Rome Air Development Center with the content equivalent to an intense course in Linear Systems . Material...is slanted toward the practicing engineer and introduces some of the fundamental concepts and techniques for analyzing linear systems . Techniques for

  20. Immune System

    NARCIS (Netherlands)

    Kuper, C.F.; Ruehl-Fehlert, C.; Elmore, S.A.; Parker, G.A.

    2013-01-01

    Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion t

  1. Caste System

    OpenAIRE

    Hoff, Karla

    2016-01-01

    In standard economics, individuals are rational actors and economic forces undermine institutions that impose large inefficiencies. The persistence of the caste system is evidence of the need for psychologically more realistic models of decision-making in economics. The caste system divides South Asian society into hereditary groups whose lowest ranks are represented as innately polluted. ...

  2. Creative Systems

    DEFF Research Database (Denmark)

    Manelius, Anne-Mette; Beim, Anne

    2007-01-01

    Opsamling af diskussioner på konferencen og udstillingen Creative Systems i september/oktober 2007. Konferencen og Udstillingen Creative Systems sætter fokus på systemer som en positiv drivkraft i den kreative skabelsesproces. CINARK inviterede fire internationale kapaciteter, som indenfor hver...... deres felt har beskæftiget sig med udviklingen af systemer. Kieran Timberlake, markant amerikansk tegnestue; Mark West, Professor på University of Manitoba, Canada, og pioner indenfor anvendelse af tekstilforskalling til betonstøbninger; Matilda McQuaid, Arkitekturhistoriker og kurator på udstillingen...... om Extreme Textiles på amerikanske Cooper Hewit Design Museum, samt Professor Ludger Hovestadt, ved ETH, Zürich der fokuserer på udvikling og anvendelse af logaritmiske systemtilgange. Udstillingen diskuterede ud fra deres meget forskellige arbejder, det kreative potentiale i anvendelsen af systemer...

  3. Power system

    Science.gov (United States)

    Hickam, Christopher Dale

    2008-03-18

    A power system includes a prime mover, a transmission, and a fluid coupler having a selectively engageable lockup clutch. The fluid coupler may be drivingly connected between the prime mover and the transmission. Additionally, the power system may include a motor/generator drivingly connected to at least one of the prime mover and the transmission. The power-system may also include power-system controls configured to execute a control method. The control method may include selecting one of a plurality of modes of operation of the power system. Additionally, the control method may include controlling the operating state of the lockup clutch dependent upon the mode of operation selected. The control method may also include controlling the operating state of the motor/generator dependent upon the mode of operation selected.

  4. Reactive Systems

    DEFF Research Database (Denmark)

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand

    A reactive system comprises networks of computing components, achieving their goals through interaction among themselves and their environment. Thus even relatively small systems may exhibit unexpectedly complex behaviours. As moreover reactive systems are often used in safety critical systems......, the need for mathematically based formal methodology is increasingly important. There are many books that look at particular methodologies for such systems. This book offers a more balanced introduction for graduate students and describes the various approaches, their strengths and weaknesses, and when...... they are best used. Milner's CCS and its operational semantics are introduced, together with the notions of behavioural equivalences based on bisimulation techniques and with recursive extensions of Hennessy-Milner logic. In the second part of the book, the presented theories are extended to take timing issues...

  5. Dynamical systems

    CERN Document Server

    Sternberg, Shlomo

    2010-01-01

    Celebrated mathematician Shlomo Sternberg, a pioneer in the field of dynamical systems, created this modern one-semester introduction to the subject for his classes at Harvard University. Its wide-ranging treatment covers one-dimensional dynamics, differential equations, random walks, iterated function systems, symbolic dynamics, and Markov chains. Supplementary materials offer a variety of online components, including PowerPoint lecture slides for professors and MATLAB exercises.""Even though there are many dynamical systems books on the market, this book is bound to become a classic. The the

  6. Physical Systems

    CERN Document Server

    Belkind, Ori

    2012-01-01

    Based on the concept of a physical system, this book offers a new philosophical interpretation of classical mechanics and the Special Theory of Relativity. According to Belkind's view the role of physical theory is to describe the motions of the parts of a physical system in relation to the motions of the whole. This approach provides a new perspective into the foundations of physical theory, where motions of parts and wholes of physical systems are taken to be fundamental, prior to spacetime, material properties and laws of motion. He defends this claim with a constructive project, deriving b

  7. Creative systems

    DEFF Research Database (Denmark)

    Beim, Anne

    2007-01-01

    At udvikle systemer har altid været et væsentligt element i den arkitektoniske skabelsesproces. Systemer er ikke nødvendigvis begrænsninger, men kan ses som positive faktorer i skabelses og fremstillinsprocessen. Center for Industriel Arkitektur, Cinark, har afholdt en international konference, en...... workshop og en udstilling under overskriften; Creative Systems. Artiklen præsenterer de fire oplægsholdere Matilda McQuaid, Mark West, Stephen Kieran og Ludger Hovestadt og en række diskussionstemaer....

  8. Recommender Systems

    CERN Document Server

    Lü, Linyuan; Yeung, Chi Ho; Zhang, Yi-Cheng; Zhang, Zi-Ke; Zhou, Tao

    2012-01-01

    The ongoing rapid expansion of the Internet greatly increases the necessity of effective recommender systems for filtering the abundant information. Extensive research for recommender systems is conducted by a broad range of communities including social and computer scientists, physicists, and interdisciplinary researchers. Despite substantial theoretical and practical achievements, unification and comparison of different approaches are lacking, which impedes further advances. In this article, we review recent developments in recommender systems and discuss the major challenges. We compare and evaluate available algorithms and examine their roles in the future developments. In addition to algorithms, physical aspects are described to illustrate macroscopic behavior of recommender systems. Potential impacts and future directions are discussed. We emphasize that recommendation has a great scientific depth and combines diverse research fields which makes it of interests for physicists as well as interdisciplinar...

  9. Avionics Systems

    Directory of Open Access Journals (Sweden)

    P.M. Soundar Rajan

    2013-03-01

    Full Text Available ‘Avionics’ systems, over the decades, have grown from simple communication radios and navigation equipments to complex integrated equipments primarily infiuenced by dominance of digital technology. Continuous growth in integrated circuit technology, functional integration of complete system on chip, very high speed communication channels and fault tolerant communication protocols have brought remarkable advancements in avionics systems. Further Mechanical and Pneumatic functional blocks are being replaced by digital systems progressively and decisively. New generation aircraft are being built around powerful avionics assets to provide stress free cockpit to the pilot.Defence Science Journal, 2013, 63(2, pp.129-130, DOI:http://dx.doi.org/10.14429/dsj.63.4269

  10. AEG System -

    Data.gov (United States)

    Department of Transportation — The AEG System is used to create, revise, approve, and distribute text of the AEGS and Flight Standard Board (FSB)/Type Rating Report. The MMEL specifies under what...

  11. Bubble systems

    CERN Document Server

    Avdeev, Alexander A

    2016-01-01

    This monograph presents a systematic analysis of bubble system mathematics, using the mechanics of two-phase systems in non-equilibrium as the scope of analysis. The author introduces the thermodynamic foundations of bubble systems, ranging from the fundamental starting points to current research challenges. This book addresses a range of topics, including description methods of multi-phase systems, boundary and initial conditions as well as coupling requirements at the phase boundary. Moreover, it presents a detailed study of the basic problems of bubble dynamics in a liquid mass: growth (dynamically and thermally controlled), collapse, bubble pulsations, bubble rise and breakup. Special emphasis is placed on bubble dynamics in turbulent flows. The analysis results are used to write integral equations governing the rate of vapor generation (condensation) in non-equilibrium flows, thus creating a basis for solving a number of practical problems. This book is the first to present a comprehensive theory of boil...

  12. Health systems

    DEFF Research Database (Denmark)

    Büchner, Vera Antonia; Hinz, Vera; Schreyögg, Jonas

    2016-01-01

    This study investigates potential changes in hospital performance after health system entry, while differentiating between hospital technical and cost efficiency and hospital profitability. In the first stage we obtained (bootstrapped) data envelopment analysis (DEA) efficiency scores. Then......, genetic matching is used as a novel matching procedure in this context along with a difference-in-difference approach within a panel regression framework. With the genetic matching procedure, independent and health system hospitals are matched along a number of environmental and organizational...... characteristics. The results show that health system entry increases hospital technical and cost efficiency by between 0.6 and 3.4 % in four alternative post-entry periods, indicating that health system entry has not a transitory but rather a permanent effect on hospital efficiency. Regarding hospital...

  13. Bitcoin System

    National Research Council Canada - National Science Library

    Jan Lánský

    2017-01-01

    .... Bitcoin is the first and also the most widespread cryptocurrency. The aim of this article is to introduce Bitcoin system using a language understandable also to readers without computer science education...

  14. Sleep loss and cytokines levels in an experimental model of psoriasis.

    Directory of Open Access Journals (Sweden)

    Camila Hirotsu

    Full Text Available Up to 80% of people develop a cutaneous condition closely connected to their exposure to stressful life events. Psoriasis is a chronic recurrent inflammatory skin disorder with multifactorial etiology, including genetic background, environmental factors, and immune system disturbances with a strong cytokine component. Moreover, psoriasis is variably associated with sleep disturbance and sleep deprivation. This study evaluated the influence of sleep loss in the context of an animal model of psoriasis by measuring cytokine and stress-related hormone levels. Male adult Balb/C mice with or without psoriasis were subjected to 48 h of selective paradoxical sleep deprivation (PSD. Sleep deprivation potentiated the activities of kallikrein-5 and kallikrein-7 in the skin of psoriatic groups. Also, mice with psoriasis had significant increases in specific pro-inflammatory cytokines (IL-1β, IL-6 and IL-12 and decreases in the anti-inflammatory cytokine (IL-10 after PSD, which were normalized after 48 h of sleep rebound. Linear regression showed that IL-2, IL-6 and IL-12 levels predicted 66% of corticosterone levels, which were selectively increased in psoriasis mice subject to PSD. Kallikrein-5 was also correlated with pro-inflammatory cytokines, explaining 58% of IL-6 and IL-12 variability. These data suggest that sleep deprivation plays an important role in the exacerbation of psoriasis through modulation of the immune system in the epidermal barrier. Thus, sleep loss should be considered a risk factor for the development of psoriasis.

  15. Systems failure.

    OpenAIRE

    Macleod, Anna

    1998-01-01

    Systems Failure A solo exhibition of new work by Anna Macleod developed in conversation with curator Liz Burns. The Dock, Carrick on Shannon, Co Leitrim. Ireland. 12th February – 17th April 2010. The works for the exhibition Systems Failure include drawings, prints and small constructions that examine the delicate balance that exists between need and aspects of failure rooted in the relationship between humanity and land use. The work seeks to question the relationship between scient...

  16. Nanorobotic Systems

    Directory of Open Access Journals (Sweden)

    Lixin Dong

    2008-11-01

    Full Text Available Two strategies towards the realization of nanotechnology have been presented, i.e., top-down and bottom up. The former one is mainly based on nanofabrication and includes technologies such as nano-lithography, nano-imprint, and etching. Presently, they are still 2D fabrication processes with low resolution. The later one is an assembly-based technique. At present, it includes such items as self-assembly, dip-pen lithography, and directed self-assembly. These techniques can generate regular nano patterns in large scales. To fabricate 3D complex nano devices there are still no effective ways by so far. Here we show our effort on the development of a nano laboratory, a prototype nanomanufacturing system, based on nanorobotic manipulations. In which, we take a hybrid strategy as shown in Fig. 1. In this system, nano fabrication and nano assembly can be performed in an arbitrary order to construct nano building blocks and finally nano devices. The most important feature in this system is that the products can be fed back into the system to shrink the system part by part leading to nanorobots. Property characterization can be performed in each intermediate process. Due to the nanorobotic manipulation system, dynamic measurement can be performed rather than conventional static observations.

  17. System-of-Systems Complexity

    Directory of Open Access Journals (Sweden)

    Hermann Kopetz

    2013-11-01

    Full Text Available The global availability of communication services makes it possible to interconnect independently developed systems, called constituent systems, to provide new synergistic services and more efficient economic processes. The characteristics of these new Systems-of-Systems are qualitatively different from the classic monolithic systems. In the first part of this presentation we elaborate on these differences, particularly with respect to the autonomy of the constituent systems, to dependability, continuous evolution, and emergence. In the second part we look at a SoS from the point of view of cognitive complexity. Cognitive complexity is seen as a relation between a model of an SoS and the observer. In order to understand the behavior of a large SoS we have to generate models of adequate simplicity, i.e, of a cognitive complexity that can be handled by the limited capabilities of the human mind. We will discuss the importance of properly specifying and placing the relied-upon message interfaces between the constituent systems that form an open SoS and discuss simplification strategies that help to reduce the cognitive complexity.

  18. Systems Studies

    Energy Technology Data Exchange (ETDEWEB)

    Graham, R.L.

    1998-03-17

    The Systems Studies Activity had two objectives: (1) to investigate nontechnical barriers to the deployment of biomass production and supply systems and (2) to enhance and extend existing systems models of bioenergy supply and use. For the first objective, the Activity focused on existing bioenergy markets. Four projects were undertaken: a comparative analysis of bioenergy in Sweden and Austria; a one-day workshop on nontechnical barriers jointly supported by the Production Systems Activity; the development and testing of a framework for analyzing barriers and drivers to bioenergy markets; and surveys of wood pellet users in Sweden, Austria and the US. For the second objective, two projects were undertaken. First, the Activity worked with the Integrated BioEnergy Systems (TBS) Activity of TEA Bioenergy Task XIII to enhance the BioEnergy Assessment Model (BEAM). This model is documented in the final report of the IBS Activity. The Systems Studies Activity contributed to enhancing the feedstock portion of the model by developing a coherent set of willow, poplar, and switchgrass production modules relevant to both the US and the UK. The Activity also developed a pretreatment module for switchgrass. Second, the Activity sponsored a three-day workshop on modeling bioenergy systems with the objectives of providing an overview of the types of models used to evaluate bioenergy and promoting communication among bioenergy modelers. There were nine guest speakers addressing different types of models used to evaluate different aspects of bioenergy, ranging from technoeconomic models based on the ASPEN software to linear programming models to develop feedstock supply curves for the US. The papers from this workshop have been submitted to Biomass and Bioenergy and are under editorial review.

  19. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  20. Systemic trauma.

    Science.gov (United States)

    Goldsmith, Rachel E; Martin, Christina Gamache; Smith, Carly Parnitzke

    2014-01-01

    Substantial theoretical, empirical, and clinical work examines trauma as it relates to individual victims and perpetrators. As trauma professionals, it is necessary to acknowledge facets of institutions, cultures, and communities that contribute to trauma and subsequent outcomes. Systemic trauma-contextual features of environments and institutions that give rise to trauma, maintain it, and impact posttraumatic responses-provides a framework for considering the full range of traumatic phenomena. The current issue of the Journal of Trauma & Dissociation is composed of articles that incorporate systemic approaches to trauma. This perspective extends conceptualizations of trauma to consider the influence of environments such as schools and universities, churches and other religious institutions, the military, workplace settings, hospitals, jails, and prisons; agencies and systems such as police, foster care, immigration, federal assistance, disaster management, and the media; conflicts involving war, torture, terrorism, and refugees; dynamics of racism, sexism, discrimination, bullying, and homophobia; and issues pertaining to conceptualizations, measurement, methodology, teaching, and intervention. Although it may be challenging to expand psychological and psychiatric paradigms of trauma, a systemic trauma perspective is necessary on both scientific and ethical grounds. Furthermore, a systemic trauma perspective reflects current approaches in the fields of global health, nursing, social work, and human rights. Empirical investigations and intervention science informed by this paradigm have the potential to advance scientific inquiry, lower the incidence of a broader range of traumatic experiences, and help to alleviate personal and societal suffering.

  1. Turbine system

    Energy Technology Data Exchange (ETDEWEB)

    McMahan, Kevin Weston; Dillard, Daniel Jackson

    2016-05-03

    A turbine system is disclosed. The turbine system includes a transition duct having an inlet, an outlet, and a passage extending between the inlet and the outlet and defining a longitudinal axis, a radial axis, and a tangential axis. The outlet of the transition duct is offset from the inlet along the longitudinal axis and the tangential axis. The turbine system further includes a turbine section connected to the transition duct. The turbine section includes a plurality of shroud blocks at least partially defining a hot gas path, a plurality of buckets at least partially disposed in the hot gas path, and a plurality of nozzles at least partially disposed in the hot gas path. At least one of a shroud block, a bucket, or a nozzle includes means for withstanding high temperatures.

  2. System Description:

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Poswolsky, Adam

    2009-01-01

    Delphin is a functional programming language [Adam Poswolsky and Carsten Schürmann. Practical programming with higher-order encodings and dependent types. In European Symposium on Programming (ESOP), 2008] utilizing dependent higher-order datatypes. Delphin's two-level type-system cleanly separates...... data from computation, allowing for decidable type checking. The data level is LF [Robert Harper, Furio Honsell, and Gordon Plotkin. A framework for defining logics. Journal of the Association for Computing Machinery, 40(1):143-184, January 1993], which allows for the specification of deductive systems...

  3. Lubrication system

    Energy Technology Data Exchange (ETDEWEB)

    Wadding, C.; Lagasse, N.L.; Milo, G.T.; Vankamerik, J.G.

    1986-02-11

    This patent describes a lubrication system for controlling the flow of lubricant as a function of the altitude at which a gas turbine engine is operating. This lubrication system is comprised of: 1.) A source of lubricant under pressure; 2.) A unit requiring lubrication; 3.) A movable valve in fluid communication with the source and with the unit for regulating the flow of lubricant from the source to the unit; and 4.) An altitude sensor associated with the movable valve for positioning the movable valve to control the flow of lubricant from the source to the unit, as a function of the altitude at which the engine is operating.

  4. Microbiology System

    Science.gov (United States)

    1992-01-01

    Technology originating in a NASA-sponsored study of the measurement of microbial growth in zero gravity led to the development of Biomerieux Vitek, Inc.'s VITEK system. VITEK provides a physician with accurate diagnostic information and identifies the most effective medication. Test cards are employed to identify organisms and determine susceptibility to antibiotics. A photo-optical scanner scans the card and monitors changes in the growth of cells contained within the card. There are two configurations - VITEK and VITEK JR as well as VIDAS, a companion system that detects bacteria, viruses, etc. from patient specimens. The company was originally created by McDonnell Douglas, the NASA contractor.

  5. [Systemic scleroderma].

    Science.gov (United States)

    Hunzelmann, N

    2013-04-01

    Systemic scleroderma is a chronic autoimmune disease affecting the skin, internal organs and the musculoskeletal system. The presence of Raynaud phenomenon, anti-nuclear antibodies and pathologic capillaroscopy are early signs of the disease. Limited cutaneous SSc, diffuse cutaneous SSc and SSc-overlap syndromes are the main clinical subtypes. Multidisciplinary care is mandatory. Follow-up examinations should be performed at least annually in order to recognize in a timely fashion treatable organ involvement such as pulmonary arterial hypertension. Besides symptomatic treatment of organ involvement, immunosuppressive therapy is indicated for a progressive inflammatory course.

  6. Computer systems

    Science.gov (United States)

    Olsen, Lola

    1992-01-01

    In addition to the discussions, Ocean Climate Data Workshop hosts gave participants an opportunity to hear about, see, and test for themselves some of the latest computer tools now available for those studying climate change and the oceans. Six speakers described computer systems and their functions. The introductory talks were followed by demonstrations to small groups of participants and some opportunities for participants to get hands-on experience. After this familiarization period, attendees were invited to return during the course of the Workshop and have one-on-one discussions and further hands-on experience with these systems. Brief summaries or abstracts of introductory presentations are addressed.

  7. Role of HMW kininogen in surface-mediated activation of Factor XII.

    Science.gov (United States)

    Shimada, T; Sugo, T; Kato, H; Iwanaga, S

    1983-01-01

    We have shown that bovine HMW kininogen remarkably accelerates the activation of Factor XII and prekallikrein in the presence of kaolin, adsorbing on kaolin through the fragment 1.2 region and forming a complex with prekallikrein through the light chain region (Sugo et al., 1980; Ikari et al., 1981). The present study was undertaken to examine the role of HMW kininogen in the activation of Factor XII and prekallikrein with other negatively-charged surfaces. The activation system used here was as follows; (1) Activation of prekallikrein by Factor XII, (2) Activation of Factor XII by plasma kallikrein and (3) Activation of prekallikrein by Factor XIIa. Among a variety of foreign surfaces, amylose sulfate and sulfatide were the most efficient in the activation reaction of Factor XII and prekallikrein. Bovene HMW kininogen accelerated all the three reactions triggered by these surfaces. However, the accelerating effect of HMW kininogen on the activation of Factor XII by plasma kallikrein was very weak, when amylose sulfate or sulfatide was used as surface. The three reactions were highly dependent on the amounts of HMW kininogen and surfaces contained in the reaction mixtures. Excess amount of them inhibited these reactions. Among the various fragments, which were prepared from HMW kininogen digests with plasma and urinary kallikreins (Sugo et al., 1980), a large fragment consisting of fragment 1.2 and light chain accelerated the reactions. Thus both fragment 1.2 and the light chain region in HMW kininogen were essential for these activation reactions.

  8. A Kallikrein 15 (KLK15 single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

    Directory of Open Access Journals (Sweden)

    Song Honglin

    2011-04-01

    Full Text Available Abstract Background KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival. Results In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319. In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR 1.42, 95% CI 1.02-1.96. This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34. This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site. Conclusions We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival.

  9. Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels

    NARCIS (Netherlands)

    Portelli, Michael A.; Siedlinski, Mateusz; Stewart, Ceri E.; Postma, Dirkje S.; Nieuwenhuis, Maartje A.; Vonk, Judith M.; Nurnberg, Peter; Altmuller, Janine; Moffatt, Miriam F.; Wardlaw, Andrew J.; Parker, Stuart G.; Connolly, Martin J.; Koppelman, Gerard H.; Sayers, Ian

    2014-01-01

    The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease agg

  10. Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels

    OpenAIRE

    Portelli, Michael; Siedlinski, Mateusz; Stewart, Ceri E.; Postma, Dirkje S; Nieuwenhuis, Maartje A.; Vonk, Judith M; Nurnberg, Peter; Altmuller, Janine; Moffatt, M. F.; Wardlaw, Andrew J.; Parker, Stuart G; Connolly, Martin J.; Koppelman, Gerard H; Sayers, Ian

    2014-01-01

    The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonar...

  11. Irrigation System

    Science.gov (United States)

    1984-01-01

    Under contract with Marshall Space Flight Center, Midwest Research Institute compiled a Lubrication Handbook intended as a reference source for designers and manufacturers of aerospace hardware and crews responsible for maintenance of such equipment. Engineers of Lindsay Manufacturing Company learned of this handbook through NASA Tech Briefs and used it for supplemental information in redesigning gear boxes for their center pivot agricultural irrigation system.

  12. Immune System

    Science.gov (United States)

    ... and mature there to become B cells or leave for the thymus gland, where they mature to become T cells. B lymphocytes and T lymphocytes have separate jobs to do: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses to ...

  13. Bricks / Systems

    DEFF Research Database (Denmark)

    and systems. The basis for this theme is the work conducted at the Utzon(x) Research Group at Aalborg University, in combination with the rich tradition and implementation of masonry work in Denmark, which has attracted increasing attention from architectural practitioners and researchers alike. How should...

  14. Multiagent systems

    National Research Council Canada - National Science Library

    Sycara, Katia P

    1998-01-01

    ... of such multiagent systems (MASs) are a core set of issues and research questions that have been studied over the years by the distributed AT community. In this article, I present some of the critical notions in MASs and the research work that has addressed them. I organize these notions around the concept of problem-solving coherence,...

  15. System Dynamics

    Science.gov (United States)

    Morecroft, John

    System dynamics is an approach for thinking about and simulating situations and organisations of all kinds and sizes by visualising how the elements fit together, interact and change over time. This chapter, written by John Morecroft, describes modern system dynamics which retains the fundamentals developed in the 1950s by Jay W. Forrester of the MIT Sloan School of Management. It looks at feedback loops and time delays that affect system behaviour in a non-linear way, and illustrates how dynamic behaviour depends upon feedback loop structures. It also recognises improvements as part of the ongoing process of managing a situation in order to achieve goals. Significantly it recognises the importance of context, and practitioner skills. Feedback systems thinking views problems and solutions as being intertwined. The main concepts and tools: feedback structure and behaviour, causal loop diagrams, dynamics, are practically illustrated in a wide variety of contexts from a hot water shower through to a symphony orchestra and the practical application of the approach is described through several real examples of its use for strategic planning and evaluation.

  16. Systems chemistry

    NARCIS (Netherlands)

    Ludlow, R. Frederick; Otto, Sijbren

    2008-01-01

    The study of complex mixtures of interacting synthetic molecules has historically not received much attention from chemists, even though research into complexity is well established in the neighbouring fields. However, with the huge recent interest in systems biology and the availability of modern a

  17. Transport system

    NARCIS (Netherlands)

    Drenth, K.F.

    1999-01-01

    The transport system comprises at least one road surface (2) and at least one vehicle (4) on wheels (6). The road surface (2) has a substantially bowl-shaped cross section and the vehicle (4) is designed so that the wheels (6) run directly on the road surface (2) while the road surface (2) acts as a

  18. Solar system

    CERN Document Server

    Homer, Charlene

    2007-01-01

    Thrill young astronomers with a journey through our Solar System. Find out all about the Inner and Outer Planets, the Moon, Stars, Constellations, Asteroids, Meteors and Comets. Using simplified language and vocabulary, concepts such as planetary orbits, the asteroid belt, the lunar cycle and phases of the moon, and shooting stars are all explored.

  19. Quorum Systems

    DEFF Research Database (Denmark)

    Förster, Klaus-Tycho

    2017-01-01

    What happens if a single server is no longer powerful enough to service all your customers? The obvious choice is to add more servers and to use the majority approach (e.g. Paxos, Chapter 2) to guarantee consistency. However, even if you buy one million servers, a client still has to access more ...... study the theory behind overlapping sets, known as quorum systems....

  20. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  1. Systems Chronotherapeutics

    Science.gov (United States)

    Innominato, Pasquale F.; Dallmann, Robert; Rand, David A.; Lévi, Francis A.

    2017-01-01

    Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected in regulatory feedback loops. They are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker, which also adjusts the circadian rhythms to environmental cycles. As a result, many mechanisms of diseases and drug effects are controlled by the circadian timing system. Thus, the tolerability of nearly 500 medications varies by up to fivefold according to circadian scheduling, both in experimental models and/or patients. Moreover, treatment itself disrupted, maintained, or improved the circadian timing system as a function of drug timing. Improved patient outcomes on circadian-based treatments (chronotherapy) have been demonstrated in randomized clinical trials, especially for cancer and inflammatory diseases. However, recent technological advances have highlighted large interpatient differences in circadian functions resulting in significant variability in chronotherapy response. Such findings advocate for the advancement of personalized chronotherapeutics through interdisciplinary systems approaches. Thus, the combination of mathematical, statistical, technological, experimental, and clinical expertise is now shaping the development of dedicated devices and diagnostic and delivery algorithms enabling treatment individualization. In particular, multiscale systems chronopharmacology approaches currently combine mathematical modeling based on cellular and whole-body physiology to preclinical and clinical investigations toward the design of patient-tailored chronotherapies. We review recent systems research works aiming to the individualization of disease treatment, with emphasis on both cancer management and circadian timing system–resetting strategies for improving chronic disease control and

  2. Exploring Enterprise, System of Systems, and System and Software Architectures

    Science.gov (United States)

    2016-06-13

    2009 Carnegie Mellon University Exploring Enterprise, System of Systems, and System and Software Architectures Software Engineering Institute...TITLE AND SUBTITLE Exploring Enterprise, System of Systems, and System and Software Architectures 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...Carnegie Mellon University, Software Engineering Institute,Pittsburgh,PA,15213 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY

  3. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    2012-01-01

    design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational......-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto...

  4. Decentralized Systems.

    Science.gov (United States)

    1980-12-31

    source of interrupts can be generated at each element. These interrupts can be used to sample local state information I or to maintain a measure of...adjoining identifiers or system words. 2.7.2 Synonymous Symbols For convience some operators have a number of different representations They are...of this perfor- Sr tance measure for the programs sampled . The programs executed included the Sieve of Eratosthenes described in section 2.1, a

  5. Imaging System

    Science.gov (United States)

    1995-01-01

    The 1100C Virtual Window is based on technology developed under NASA Small Business Innovation (SBIR) contracts to Ames Research Center. For example, under one contract Dimension Technologies, Inc. developed a large autostereoscopic display for scientific visualization applications. The Virtual Window employs an innovative illumination system to deliver the depth and color of true 3D imaging. Its applications include surgery and Magnetic Resonance Imaging scans, viewing for teleoperated robots, training, and in aviation cockpit displays.

  6. Blackboard Systems.

    Science.gov (United States)

    1986-06-01

    article stated that although the importance of context, syntax, semantics, and phonological rules in the recognition of speech was accepted, no system had...of, from the lowest to the highest level: parametric, segmental, phonetic , phonemic, syllabic, lexical, phrasal, and conceptual levels (see Figure 3...from classification (classifying acoustic segments into phonetic classes), to recognition (recognizing words) to generation and 42SCe (25] for a

  7. Systemic Assurance

    Science.gov (United States)

    2015-07-31

    simulations, cyber-physical robotic systems, and extremely large commercial Java programs. An important goal is to develop incrementally compostable...randomness and stochastic behavior, both as integral to algorithm design and as a consequence of multi- threading , (3) Concurrency and distribution, as the...should be involved in all four threads of the effort: Baseline Analysis of Codified Best Practices The baselining analysis for existing practices has

  8. Security system

    Science.gov (United States)

    Baumann, Mark J.; Kuca, Michal; Aragon, Mona L.

    2016-02-02

    A security system includes a structure having a structural surface. The structure is sized to contain an asset therein and configured to provide a forceful breaching delay. The structure has an opening formed therein to permit predetermined access to the asset contained within the structure. The structure includes intrusion detection features within or associated with the structure that are activated in response to at least a partial breach of the structure.

  9. Gasification system

    Science.gov (United States)

    Haldipur, Gaurang B.; Anderson, Richard G.; Cherish, Peter

    1983-01-01

    A method and system for injecting coal and process fluids into a fluidized bed gasification reactor. Three concentric tubes extend vertically upward into the fluidized bed. Coal particulates in a transport gas are injected through an inner tube, and an oxygen rich mixture of oxygen and steam are injected through an inner annulus about the inner tube. A gaseous medium relatively lean in oxygen content, such as steam, is injected through an annulus surrounding the inner annulus.

  10. Propulsion Systems

    Science.gov (United States)

    2011-03-31

    definition we are choosing x to be aligned with the direction of flight. Thus, accounting for the possible rotation of the axes, the acceleration in...Monopropellants. In a monopropellant system, like the name suggests, there is one propellant which decomposes exothermically as it passes through a catalytic...it comes into contact with the catalyst bed. Subsequently, the ammonia decomposes into nitrogen and hydrogen in an endothermic reaction lowering the

  11. Ongoing contact activation in patients with hereditary angioedema.

    Directory of Open Access Journals (Sweden)

    Joke Konings

    Full Text Available Hereditary angioedema (HAE is predominantly caused by a deficiency in C1 esterase inhibitor (C1INH (HAE-C1INH. C1INH inhibits activated factor XII (FXIIa, activated factor XI (FXIa, and kallikrein. In HAE-C1INH patients the thrombotic risk is not increased even though activation of the contact system is poorly regulated. Therefore, we hypothesized that contact activation preferentially leads to kallikrein formation and less to activation of the coagulation cascade in HAE-C1INH patients. We measured the levels of C1INH in complex with activated contact factors in plasma samples of HAE-C1INH patients (N=30, 17 during remission and 13 during acute attack and healthy controls (N=10. We did not detect differences in enzyme-inhibitor complexes between samples of controls, patients during remission and patients during an acute attack. Reconstitution with C1INH did not change this result. Next, we determined the potential to form enzyme-inhibitory complexes after complete in vitro activation of the plasma samples with a FXII trigger. In all samples, enzyme-C1INH levels increased after activation even in patients during an acute attack. However, the levels of FXIIa-C1INH, FXIa-C1INH and kallikrein-C1INH were at least 52% lower in samples taken during remission and 70% lower in samples taken during attack compared to samples from controls (p<0.05. Addition of C1INH after activation led to an increase in levels of FXIIa-C1INH and FXIa-C1INH (p<0.05, which were still lower than in controls (p<0.05, while the levels of kallikrein-C1INH did not change. These results are consistent with constitutive activation and attenuated depletion of the contact system and show that the ongoing activation of the contact system, which is present in HAE-C1INH patients both during remission and during acute attacks, is not associated with preferential generation of kallikrein over FXIa.

  12. Law system and legislation system

    OpenAIRE

    Boshno, Svetlana

    2013-01-01

    This paper is a continuation of publication of the «Jurisprudence» textbook by Svetlana Vladimirovna Boshno. Law system is a key element of general theory of law. The major fundamentals of its construction are subject matter and method of legal regulation. Of great importance is the division of legal regulation methods into mandative and dispositive ones. The paper articulates the concepts of institute and branch of law demonstrated through various examples. An important classification of bra...

  13. Linear systems

    CERN Document Server

    Bourlès, Henri

    2013-01-01

    Linear systems have all the necessary elements (modeling, identification, analysis and control), from an educational point of view, to help us understand the discipline of automation and apply it efficiently. This book is progressive and organized in such a way that different levels of readership are possible. It is addressed both to beginners and those with a good understanding of automation wishing to enhance their knowledge on the subject. The theory is rigorously developed and illustrated by numerous examples which can be reproduced with the help of appropriate computation software. 60 exe

  14. Dynamical systems

    CERN Document Server

    Birkhoff, George D

    1927-01-01

    His research in dynamics constitutes the middle period of Birkhoff's scientific career, that of maturity and greatest power. -Yearbook of the American Philosophical Society The author's great book€¦is well known to all, and the diverse active modern developments in mathematics which have been inspired by this volume bear the most eloquent testimony to its quality and influence. -Zentralblatt MATH In 1927, G. D. Birkhoff wrote a remarkable treatise on the theory of dynamical systems that would inspire many later mathematicians to do great work. To a large extent, Birkhoff was writing about his o

  15. Nuclear systems

    CERN Document Server

    Todreas, Neil E

    2011-01-01

    Principal Characteristics of Power ReactorsIntroductionPower CyclesPrimary Coolant SystemsReactor CoresFuel AssembliesAdvanced Water- and Gas-Cooled Reactors (Generation III And III+)Advanced Thermal and Fast Neutron Spectrum Reactors (Generation IV)ReferencesProblemsThermal Design Principles and ApplicationIntroductionOverall Plant Characteristics Influenced by Thermal Hydraulic ConsiderationsEnergy Production and Transfer ParametersThermal Design LimitsThermal Design MarginFigures of Merit for Core Thermal PerformanceThe Inverted Fuel ArrayThe Equivalent Annulus ApproximationReferencesProble

  16. Expert Systems: What Is an Expert System?

    Science.gov (United States)

    Duval, Beverly K.; Main, Linda

    1994-01-01

    Describes expert systems and discusses their use in libraries. Highlights include parts of an expert system; expert system shells; an example of how to build an expert system; a bibliography of 34 sources of information on expert systems in libraries; and a list of 10 expert system shells used in libraries. (Contains five references.) (LRW)

  17. Expert Systems: What Is an Expert System?

    Science.gov (United States)

    Duval, Beverly K.; Main, Linda

    1994-01-01

    Describes expert systems and discusses their use in libraries. Highlights include parts of an expert system; expert system shells; an example of how to build an expert system; a bibliography of 34 sources of information on expert systems in libraries; and a list of 10 expert system shells used in libraries. (Contains five references.) (LRW)

  18. Systemic Planning

    DEFF Research Database (Denmark)

    Leleur, Steen

    This book presents principles and methodology for planning in a complex world. It sets out a so-called systemic approach to planning, among other things, by applying “hard” and “soft” methodologies and methods in combination. The book is written for Ph.D and graduate students in engineering......, business and other fields, and it is useful for all professionals, across a wide range of employment areas, who share an interest in renewing planning practice. Such an endeavour is seen as both important and timely, recognising that many complex planning tasks necessitate organisations – be they public...... or private – to engage in planning to prepare proactive decision-making....

  19. Model Systems

    Directory of Open Access Journals (Sweden)

    Francisco Rodríguez-Trelles

    1998-12-01

    Full Text Available Current efforts to study the biological effects of global change have focused on ecological responses, particularly shifts in species ranges. Mostly ignored are microevolutionary changes. Genetic changes may be at least as important as ecological ones in determining species' responses. In addition, such changes may be a sensitive indicator of global changes that will provide different information than that provided by range shifts. We discuss potential candidate systems to use in such monitoring programs. Studies of Drosophila subobscura suggest that its chromosomal inversion polymorphisms are responding to global warming. Drosophila inversion polymorphisms can be useful indicators of the effects of climate change on populations and ecosystems. Other species also hold the potential to become important indicators of global change. Such studies might significantly influence ecosystem conservation policies and research priorities.

  20. Cognitive Systems

    DEFF Research Database (Denmark)

    and its relation and potential over current artificial intelligence architectures. Machine learning models that learn from data and previous knowledge will play an increasingly important role in all levels of cognition as large real world digital environments (such as the Internet) usually are too complex...... to be modeled within a limited set of predefined specifications. There will inevitably be a need for robust decisions and behaviors in novel situations that include handling of conflicts and ambiguities based on the capability and knowledge of the artificial cognitive system. Further, there is a need......, cognitive psychology, and semantics. However, machine learning for signal processing plays a key role at all the levels of the cognitive processes, and we expect this to be a new emerging trend in our community in the coming years. Current examples of the use of machine learning for signal processing...

  1. Systemic Planning

    DEFF Research Database (Denmark)

    Leleur, Steen

    This book presents principles and methodology for planning in a complex world. It sets out a so-called systemic approach to planning, among other things, by applying “hard” and “soft” methodologies and methods in combination. The book is written for Ph.D and graduate students in engineering......, business and other fields, and it is useful for all professionals, across a wide range of employment areas, who share an interest in renewing planning practice. Such an endeavour is seen as both important and timely, recognising that many complex planning tasks necessitate organisations – be they public...... or private – to engage in planning to prepare proactive decision-making....

  2. Turbocompound system

    Energy Technology Data Exchange (ETDEWEB)

    Fox, L.D.

    1986-05-06

    A turbocompound system is described for improving the performance of an internal combustion engine without substantially increasing an end viewed profile of the engine to which it is mounted in use. The system consists of: (a) an exhaust driven turbocharger means having an exhaust manifold means extending in an axial direction for collecting exhaust gases from engine cylinders and delivering the gases to an outlet end thereof, exhaust turbine means for extracting energy from the exhaust gases, the exhaust turbine means being provided with an inlet connected to the outlet end of the manifold and an outlet for discharging the exhaust gases, compressor means coupled to the exhaust turbine means for providing a supply of charge air under pressure to an air outlet thereof for delivery to air intake means of an internal combustion engine in use; (b) a power turbine means for extracting additional energy from the exhaust gases, the power turbine means having an intake connected to the outlet of the exhaust turbine means, and mounting means on a side of the power turbine means facing in a direction parallel to the axial direction of the exhaust manifold means that is constructed for being mounted, in use, on an end of an engine adjacent one end of a crankshaft of the engine; and (c) coupling means connected to the power turbine means for transferring mechanical energy produced by the power turbine means, the coupling means extending from the power turbine means to a power take-off end in a direction parallel to the axial length of the exhaust manifold means by an amount that is sufficient for enabling the power take-off end to be connected, in use, to an opposite end of the engine crankshaft from the one end thereof in a manner for transferring the mechanical energy produced by the power turbine means adjacent the one end of the crankshaft to the opposite end of the crankshaft without having to pass therethrough.

  3. Systems engineering simplified

    CERN Document Server

    Cloutier, Robert; Bone, Mary Alice

    2015-01-01

    IntroductionOverviewDiscussion of Common TerminologyThe Case for Systems EngineeringA Brief History of Systems EngineeringSystem ExamplesSummaryThe System Life CycleManaging System Development-The Vee ModelSystem ProductionSystem Utilization and SupportSystem Retirement and DisposalOther Systems Engineering Development ModelsSpiral ModelAgile Model for Systems EngineeringSystem of InterestAbstraction and DecompositionIntegrationDeveloping and Managing RequirementsCyclone Requiremen

  4. SwissProt search result: AK109059 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109059 002-154-F02 (P03952) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_HUMAN 1e-27 ...

  5. SwissProt search result: AK061101 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061101 006-207-A12 (P26262) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_MOUSE 3e-34 ...

  6. SwissProt search result: AK061101 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061101 006-207-A12 (P14272) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_RAT 7e-33 ...

  7. SwissProt search result: AK112005 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112005 006-202-F10 (P26262) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_MOUSE 9e-25 ...

  8. SwissProt search result: AK112119 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112119 006-303-H09 (P03952) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_HUMAN 2e-21 ...

  9. SwissProt search result: AK112119 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112119 006-303-H09 (P26262) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_MOUSE 3e-25 ...

  10. SwissProt search result: AK061101 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061101 006-207-A12 (P03952) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_HUMAN 4e-37 ...

  11. SwissProt search result: AK112119 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112119 006-303-H09 (P14272) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_RAT 8e-24 ...

  12. SwissProt search result: AK112005 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112005 006-202-F10 (P03952) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_HUMAN 5e-21 ...

  13. SwissProt search result: AK112005 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112005 006-202-F10 (P14272) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_RAT 2e-23 ...

  14. SwissProt search result: AK109059 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109059 002-154-F02 (P26262) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_MOUSE 8e-27 ...

  15. SwissProt search result: AK109059 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109059 002-154-F02 (P14272) Plasma kallikrein precursor (EC 3.4.21.34) (Plasma prekallikre...in) (Kininogenin) (Fletcher factor) [Contains: Plasma kallikrein heavy chain; Plasma kallikrein light chain] KLKB1_RAT 1e-26 ...

  16. Cardiovascular System

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    7.1 Heart failure2007175 Effects of recombinant human brain natriuretic peptide on aldosterone and endothelin-1 in treatment of heart failure. FU Yao(付尧),et al. Dept Cardiol, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin Cir J 2007;22(1):35-37. Obiective To study the efficacy and the effects of recombinant human brain natriuretic peptide(rhBNP) on aldosterone and endothelin-1 in the treatment of congestive heart failure(CHF).Methods A randomized, open, controlled clinical trial was conducted in 35 patients with CHF. Eighteen received rhBNP and 17 were treated with nitroglycerin as controls. The changes hemodynamic indexes, the plasma concentrations of K+, Na+, aldo-sterone(ALD) and endothelin-1 (ET-1) in order to examine the efficacy and mechanism of rhBNP. Results Between experiment and control groups significant differences were found in the decreasing of PCWP, PAP and plasma concentration of Na+, ALD, ET-1, and in the increasing of plasma concentration of K+ (P<0.05~0.01). Conclusion The mechanism of rhBNP may be associated with the overactivation of renin-angiotension-aldosterone system, and the inhibited production of endothelin-1.

  17. Systems Biology and Health Systems Complexity in;

    NARCIS (Netherlands)

    Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.

    2016-01-01

    Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

  18. System safety education focused on system management

    Science.gov (United States)

    Grose, V. L.

    1971-01-01

    System safety is defined and characteristics of the system are outlined. Some of the principle characteristics include role of humans in hazard analysis, clear language for input and output, system interdependence, self containment, and parallel analysis of elements.

  19. Respiratory System

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    8.1 Respiratory failure2007204 Comparison of the effects of BiPAP ventilation combined with lung recruitment maneuvers and low tidal volume A/C ventilation in patients with acute respiratory distress syndrome. WANG Xiaozhi(王晓芝),et al. Dept Respir & Intensive Care Unit, Binzhou Med Coll, Binzhou 256603. Chin J Tuberc Respir Dis 2007;30(1):44-47. Objective To compare the effects of BiPAP ventilation combined with lung recruitment maneuvers(LRM) with low tidal volume A/C ventilation in patients with acute respiratory distress syndrome (ARDS). Methods A prospective, randomized comparison of BiPAP mechanical ventilation combined with lung recruitment maneuvers(test group) with low tidal volume A/C ventilation (control group) was conducted in 28 patients with ARDS. FiO2/PaO2 ratio, respiratory system compliance(Cs), central venous pressure (CVP), duration of ventilation support were recorded at 0 h, 48 h and 72 h separately. The ventilation associated lung injury and mortality at 28 d were also recorded. Results The FiO2/PaO2 ratio were (298±16) and (309±16) cm H2O, Cs were (38.4±2.2) and (42.0±1.3) ml/cm H2O, CVP were (13.8±0.8) and (11.6±0.7) cm H2O in the test group at 48 h and 72 h separately. In the control group, FiO2/PaO2 ratio were (212±12) and (246±17) cm H2O, Cs were (29.5±1.3) and (29.0±1.0) ml/cm H2O, CVP were 18.6±1.1 and (16.8±1.0) cm H2O. The results were better in the test group as compared with the control group (t=10.03-29. 68, all P<0.01). The duration of ventilation support in the test group was shorter than the control group [(14±3) d vs (19±3)d, t=4.80, P<0.01]. The mortality in 28 d and ventilation associated lung injury were similar in the two groups. Conclusion The results show that combination of LRM with BiPAP mode ventilation, as compared with the control group, contributes to the improved FiO2/PaO2 ratio, pulmonary compliance, stable homodynamic and shorter duration of ventilation support in patients with ARDs.

  20. Quality management system

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mu Sung

    2009-08-15

    This book deals with ISO9001 quality management system which includes summary of this system such as classification of quality, principle of quality management, and definition, requirement and procedure of quality management system, introduction of ISO9001 system like model of ISO9001 quality management system, ISO certificate system, structure of ISO9001 standard, requirement of ISO9001 quality management system, process approach and documentation of system, propel cases of ISO9001 quality management system.

  1. Systems theory of interconnected port contact systems

    NARCIS (Netherlands)

    Eberard, D.; Maschke, B.M.; Schaft, A.J. van der

    2005-01-01

    Port-based network modeling of a large class of complex physical systems leads to dynamical systems known as port-Hamiltonian systems. The key ingredient of any port-Hamiltonian system is a power-conserving interconnection structure (mathematically formalized by the geometric notion of a Dirac struc

  2. Protecting Information in Systems of Systems

    NARCIS (Netherlands)

    Trivellato, Daniel; Zannone, Nicola; Etalle, Sandro

    2011-01-01

    Systems of Systems (SoS) are dynamic, distributed coalitions of autonomous and heterogeneous systems that collaborate to achieve a common goal. While offering several advantages in terms of scalability and flexibility, the SoS paradigm has a strong impact on system interoperability and on the securi

  3. Advanced Systems Theory Applied to AMB Systems

    NARCIS (Netherlands)

    Balini, H.M.N.K.

    2011-01-01

    In this thesis we look at the application of advanced systems theoretic algorithms for an experimental Active Magnetic Bearing System (AMB). These systems are inherently unstable and therefore require a feedback controller. Accurate modeling of these systems with input-output data is hindered due to

  4. Square conservation systems and Hamiltonian systems

    Institute of Scientific and Technical Information of China (English)

    王斌; 曾庆存; 季仲贞

    1995-01-01

    The internal and external relationships between the square conservation scheme and the symplectic scheme are revealed by a careful study on the interrelation between the square conservation system and the Hamiltonian system in the linear situation, thus laying a theoretical basis for the application and extension of symplectic schemes to square conservations systems, and of those schemes with quadratic conservation properties to Hamiltonian systems.

  5. A Security Framework for Systems of Systems

    NARCIS (Netherlands)

    Trivellato, Daniel; Zannone, Nicola; Etalle, Sandro

    2011-01-01

    Systems of systems consist of a wide variety of dynamic, distributed coalitions of autonomous and heterogeneous systems that collaborate to achieve a common goal. While offering several advantages in terms of scalability and flexibility, this new paradigm has a strong impact on system

  6. Understanding Patterns for System of Systems Integration

    DEFF Research Database (Denmark)

    Kazman, Rick; Schmid, Klaus; Nielsen, Claus Ballegård

    2013-01-01

    of systems integration patterns. These characteristics at the same time support the architecting process by highlighting important issues a SoS architect needs to consider. We discuss the consolidated template and illustrate it with an example pattern. We also discuss the integration of this novel pattern......Architecting systems of systems is well known to be a formidable challenge. A major aspect in this is defining the integration among the systems that constitute the system of systems. In this paper, we aim to support the SoS architect by systematically developing a way to characterize system...

  7. Concept and System of Personification Control System

    Institute of Scientific and Technical Information of China (English)

    Bai,Fengshuang; Yin,Yixin; Tu,Xuyan; Zhang,Ying

    2006-01-01

    This paper provides the system and conception of the Personification Control System (PCS) on the basis of Intelligent Control System based on Artificial life (ICS/AL), Artificial Emotion, Humanoid Control, and Intelligent Control System based on Field bus. According to system science and deciding of organize of biology, the Pyramid System of PCS are created. Then Pyramid System of PCS which is made up of PCS1/H, PCS1/S, PCS1/O, PCS1/C and PCS1/G is described.

  8. Networked control of microgrid system of systems

    Science.gov (United States)

    Mahmoud, Magdi S.; Rahman, Mohamed Saif Ur; AL-Sunni, Fouad M.

    2016-08-01

    The microgrid has made its mark in distributed generation and has attracted widespread research. However, microgrid is a complex system which needs to be viewed from an intelligent system of systems perspective. In this paper, a network control system of systems is designed for the islanded microgrid system consisting of three distributed generation units as three subsystems supplying a load. The controller stabilises the microgrid system in the presence of communication infractions such as packet dropouts and delays. Simulation results are included to elucidate the effectiveness of the proposed control strategy.

  9. D0 Cryo System Control System Autodialer

    Energy Technology Data Exchange (ETDEWEB)

    Urbin, J.; /Fermilab

    1990-04-17

    The DO cryogenic system is controlled by a TI565-PLC based control system. This allows the system to be unmanned when in steady state operation. System experts will need to be contacted when system parameters exceed normal operating points and reach alarm setpoints. The labwide FIRUS system provides one alarm monitor and communication link. An autodialer provides a second and more flexible alarm monitor and communication link. The autodialer monitors contact points in the control system and after receiving indication of an alarm accesses a list of experts which it calls until it receives an acknowledgement. There are several manufacturers and distributors of autodialer systems. This EN explains the search process the DO cryo group used to fmd an autodialer system that fit the cryo system's needs and includes information and specs for the unit we chose.

  10. Integrated library systems.

    Science.gov (United States)

    Goldstein, C M

    1983-07-01

    The development of integrated library systems is discussed. The four major discussion points are (1) initial efforts; (2) network resources; (3) minicomputer-based systems; and (4) beyond library automation. Four existing systems are cited as examples of current systems.

  11. Freshwater systems; Frisch gezapft

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, J.P.

    2008-06-09

    Increasingly, providers of solar systems are also offering freshwater systems, although these are more costly than combined storage systems. The contribution discusses the pros and cons of these systems as well as the freshwater quality. (orig.)

  12. System design specification Brayton Isotope Power System (BIPS) Flight System (FS), and Ground Demonstration System (GDS)

    Energy Technology Data Exchange (ETDEWEB)

    1976-06-14

    The system design specification for ground demonstration, development, and flight qualification of a Brayton Isotope Power System (BIPS) is presented. The requirements for both a BIPS conceptual Flight System (FS) and a Ground Demonstration System (GDS) are defined.

  13. Situation awareness with systems of systems

    CERN Document Server

    Tretmans, Jan; Borth, Michael

    2013-01-01

    This book discusses various aspects, challenges, and solutions for developing systems-of-systems for situation awareness, using applications in the domain of maritime safety and security.  Topics include advanced, multi-objective visualization methods for situation awareness, stochastic outlier selection, rule-based anomaly detection, an ontology-based event model for semantic reasoning, new methods for semi-automatic generation of adapters bridging communication gaps, security policies for systems-of-systems, trust assessment, and methods to deal with the dynamics of systems-of-systems in run-time monitoring, testing, and diagnosis. Architectural considerations for designing information-centric systems-of-systems such as situation awareness systems, and an integrated demonstrator implementing many of the investigated aspects, complete the book.

  14. System of systems modeling and analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E. (Intera, Inc., Austin, TX); Shirah, Donald N.

    2005-01-01

    This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.

  15. Computer System Design System-on-Chip

    CERN Document Server

    Flynn, Michael J

    2011-01-01

    The next generation of computer system designers will be less concerned about details of processors and memories, and more concerned about the elements of a system tailored to particular applications. These designers will have a fundamental knowledge of processors and other elements in the system, but the success of their design will depend on the skills in making system-level tradeoffs that optimize the cost, performance and other attributes to meet application requirements. This book provides a new treatment of computer system design, particularly for System-on-Chip (SOC), which addresses th

  16. Smart electromechanical systems the central nervous system

    CERN Document Server

    Kurbanov, Vugar

    2017-01-01

    This book describes approaches to solving the problems of developing the central nervous system of robots (CNSR) based on smart electromechanical systems (SEMS) modules, principles of construction of the various modules of the central nervous system and variants of mathematical software CNSR in control systems for intelligent robots. It presents the latest advances in theory and practice at the Russian Academy of Sciences. Developers of intelligent robots to solve modern problems in robotics are increasingly addressing the use of the bionic approach to create robots that mimic the complexity and adaptability of biological systems. These have smart electromechanical system (SEMS), which are used in various cyber-physical systems (CPhS), and allow the functions of calculation, control, communications, information storage, monitoring, measurement and control of parameters and environmental parameters to be integrated. The behavior of such systems is based on the information received from the central nervous syst...

  17. Linking Political Systems and War Systems

    DEFF Research Database (Denmark)

    Harste, Gorm

    2009-01-01

    Decisive parts of the Western political system have demonstrated a seemingly surprising misinterpretation of military might. As Madelaine Albright has suggested, the mighty perceived themselves as "almighty". Political power seems to have invested in instrumental coercive power relations and found...... military coercion to be the appropriate mean. Using the system theory and the theory of systemic risks displayed by the German sociologist Niklas Luhmann the article demonstrates how military systems due to their own autonomy and autopoiesis do not fit into the idea of political government....... The Clausewitzian ideal of a political system that could continue its power games by means of war was moderated by Clausewitz' own analysis of "friction". How can a political system be so blind towards the possibilities of another system? What are the risks of systemic blind spots? The argument of the paper...

  18. Situation Awareness with Systems of Systems

    NARCIS (Netherlands)

    Laar, P. van de; Tretmans, J.; Borth, M.

    2013-01-01

    This book discusses various aspects, challenges, and solutions for developing systems-of-systems for situation awareness, using applications in the domain of maritime safety and security. Topics include advanced, multi-objective visualization methods for situation awareness, stochastic outlier

  19. Linking Political Systems and War Systems

    DEFF Research Database (Denmark)

    Harste, Gorm

    2009-01-01

    Decisive parts of the Western political system have demonstrated a seemingly surprising misinterpretation of military might. As Madelaine Albright has suggested, the mighty perceived themselves as "almighty". Political power seems to have invested in instrumental coercive power relations and found...... military coercion to be the appropriate mean. Using the system theory and the theory of systemic risks displayed by the German sociologist Niklas Luhmann the article demonstrates how military systems due to their own autonomy and autopoiesis do not fit into the idea of political government....... The Clausewitzian ideal of a political system that could continue its power games by means of war was moderated by Clausewitz' own analysis of "friction". How can a political system be so blind towards the possibilities of another system? What are the risks of systemic blind spots? The argument of the paper...

  20. Engine Auxiliary System Guideline: Lubricating Oil Systems

    OpenAIRE

    Linna, Joni

    2015-01-01

    This thesis was done for Wärtsilä Technical Services organization, the purpose of this work was to gather and structure information about the lubricating oil systems from the company’s internal databases, interviews with system specialists and from different literature sources covering Ship Power and Power Plant products. The outcome was a guideline, covering typical power plant and marine system descriptions, all components used in the lubricating oil system with their functional description...

  1. COMPARISON TRADITIONAL SYSTEMS OF TUNNEL FORMWORK SYSTEM

    OpenAIRE

    ERKAN, İbrahim Hakkı; Yılmaz, Ülkü Sultan; Türken, Hakan

    2011-01-01

    Tunnel formwork systems became the most widespread construction technology preferred in recent years in Turkey due to rapidity and economy. In this study, before all else, a brief information was given about the types and construction techniques of tunnel formwork systems. Then a reinforced concrete building sample was firstly modeled as it was constructed with the tunnel formwork system and secondly modeled as it was formed by a frame system with shear walls constructed by the traditional re...

  2. LCLS XTOD Attenuator System System Concept Report

    Energy Technology Data Exchange (ETDEWEB)

    Kishiyama, K; Roeben, M; Trent, J; Ryutov, D; Shen, S

    2006-04-12

    The attenuator system for the Linac Coherent Light Source (LCLS) X-ray Transport, Optics and Diagnostics (XTOD) system has been configured and analyzed by the Lawrence Livermore National Laboratory's New Technologies Engineering Division (NTED) as requested by the SLAC/LCLS program. The system layout, performance analyses and selection of the vacuum components are presented in this System Conceptual Review (SCR) report. Also included are the plans for prototype, procurement, mechanical integration, and the cost estimates.

  3. Designing information systems

    CERN Document Server

    Blethyn, Stanley G

    2014-01-01

    Designing Information Systems focuses on the processes, methodologies, and approaches involved in designing information systems. The book first describes systems, management and control, and how to design information systems. Discussions focus on documents produced from the functional construction function, users, operators, analysts, programmers and others, process management and control, levels of management, open systems, design of management information systems, and business system description, partitioning, and leveling. The text then takes a look at functional specification and functiona

  4. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering o

  5. Non linear system become linear system

    Directory of Open Access Journals (Sweden)

    Petre Bucur

    2007-01-01

    Full Text Available The present paper refers to the theory and the practice of the systems regarding non-linear systems and their applications. We aimed the integration of these systems to elaborate their response as well as to highlight some outstanding features.

  6. Expert Systems for auditing management information systems

    Directory of Open Access Journals (Sweden)

    Gheroghe Popescu

    2007-05-01

    Full Text Available Expert systems are built with the help of: specialised programming languages or expert system generators (shell. But this structure was reached after tens of years of work and research, because expert systems are nothing but pragmatic capitalisation of the results of research carried out in artificial intelligence and theory of knowledge.

  7. General Systems Theory and Instructional Systems Design.

    Science.gov (United States)

    Salisbury, David F.

    1990-01-01

    Describes basic concepts in the field of general systems theory (GST) and identifies commonalities that exist between GST and instructional systems design (ISD). Models and diagrams that depict system elements in ISD are presented, and two matrices that show how GST has been used in ISD literature are included. (11 references) (LRW)

  8. The complement system in systemic autoimmune disease

    NARCIS (Netherlands)

    Chen, Min; Daha, Mohamed R.; Kallenberg, Cees G. M.

    2010-01-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via

  9. Optical system defect propagation in ABCD systems

    DEFF Research Database (Denmark)

    McKinley, W.G.; Yura, H.T.; Hanson, Steen Grüner

    1988-01-01

    We describe how optical system defects (tilt/jitter, decenter, and despace) propagate through an arbitrary paraxial optical system that can be described by an ABCD ray transfer matrix. A pedagogical example is given that demonstrates the effect of alignment errors on a typical optical system....... © 1988 Optical Society of America...

  10. Observing System Evaluations Using GODAE Systems

    Science.gov (United States)

    2009-09-01

    Journal of Marine Systems 35...dimensional temperature fields: A first approach based on simulated observations. Journal of Marine Systems 46:85-98. Langland, R.H., and N.L. Baker...capabilities of multisatellite altimeter missions: First results with real data in the Mediterranean Sea. Journal of Marine Systems 65:190-211.

  11. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

  12. Safety Pharmacology, Toxicology and Pharmacokinetic Assessment of Human Gc Globulin (Vitamin D Binding Protein)

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Jørgensen, Charlotte Svaerke; Santoni-Rugiu, Eric

    2010-01-01

    of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day...... toxicity studies in rats and horses did not show any unwanted reactions. In a 14-day toxicology study in beagle dogs, formation of antibodies was seen and in the end of the study period, three out of four dogs showed clinical immunological reactions, which could be ascribed to the formation of antibodies...

  13. Safety pharmacology, toxicology and pharmacokinetic assesment of human Gc globulin (vitamin d binding protein)

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Jørgensen, Charlotte Sværke; Santoni Rugiu, Eric

    2010-01-01

    of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day...... toxicity studies in rats and horses did not show any unwanted reactions. In a 14-day toxicology study in beagle dogs, formation of antibodies was seen and in the end of the study period, three out of four dogs showed clinical immunological reactions, which could be ascribed to the formation of antibodies...

  14. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V

    2013-01-01

    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  15. Psychology of system design

    CERN Document Server

    Meister, D

    2014-01-01

    This is a book about systems, including: systems in which humans control machines; systems in which humans interact with humans and the machine component is relatively unimportant; systems which are heavily computerized and those that are not; and governmental, industrial, military and social systems. The book deals with both traditional systems like farming, fishing and the military, and with systems just now tentatively emerging, like the expert and the interactive computer system. The emphasis is on the system concept and its implications for analysis, design and evaluation of these many di

  16. Operating System Security

    CERN Document Server

    Jaeger, Trent

    2008-01-01

    Operating systems provide the fundamental mechanisms for securing computer processing. Since the 1960s, operating systems designers have explored how to build "secure" operating systems - operating systems whose mechanisms protect the system against a motivated adversary. Recently, the importance of ensuring such security has become a mainstream issue for all operating systems. In this book, we examine past research that outlines the requirements for a secure operating system and research that implements example systems that aim for such requirements. For system designs that aimed to

  17. Lighting system with thermal management system

    Science.gov (United States)

    Arik, Mehmet; Weaver, Stanton; Stecher, Thomas; Seeley, Charles; Kuenzler, Glenn; Wolfe, Jr., Charles; Utturkar, Yogen; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2013-05-07

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  18. Lighting system with thermal management system

    Energy Technology Data Exchange (ETDEWEB)

    Arik, Mehmet; Weaver, Stanton Earl; Stecher, Thomas Elliot; Seeley, Charles Erklin; Kuenzler, Glenn Howard; Wolfe, Jr, Charles Franklin; Utturkar, Yogen Vishwas; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2016-10-11

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  19. Systems Measures of Water Distribution System Resilience

    Energy Technology Data Exchange (ETDEWEB)

    Klise, Katherine A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Murray, Regan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Walker, La Tonya Nicole [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    Resilience is a concept that is being used increasingly to refer to the capacity of infrastructure systems to be prepared for and able to respond effectively and rapidly to hazardous events. In Section 2 of this report, drinking water hazards, resilience literature, and available resilience tools are presented. Broader definitions, attributes and methods for measuring resilience are presented in Section 3. In Section 4, quantitative systems performance measures for water distribution systems are presented. Finally, in Section 5, the performance measures and their relevance to measuring the resilience of water systems to hazards is discussed along with needed improvements to water distribution system modeling tools.

  20. Intelligent test integration system

    Science.gov (United States)

    Sztipanovits, J.; Padalkar, S.; Rodriguez-Moscoso, J.; Kawamura, K.; Purves, B.; Williams, R.; Biglari, H.

    1988-01-01

    A new test technology is described which was developed for space system integration. The ultimate purpose of the system is to support the automatic generation of test systems in real time, distributed computing environments. The Intelligent Test Integration System (ITIS) is a knowledge based layer above the traditional test system components which can generate complex test configurations from the specification of test scenarios.

  1. Autonomous photovoltaic lighting system

    OpenAIRE

    Ahmed A. A. Hafez; Montesinos Miracle, Daniel; Sudrià Andreu, Antoni

    2012-01-01

    This paper introduces a comparison between the conventional and Photovoltaic (PV) lighting systems. A simple sizing procedure for a PV stand-alone system was advised. The paper also proposes a novel PV lighting system. The proposed system is simple, compact and reliable. The system operation was investigated by thoroughly mathematical and simulation work.

  2. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  3. Operating System Performance Analyzer for Embedded Systems

    Directory of Open Access Journals (Sweden)

    Shahzada Khayyam Nisar

    2011-11-01

    Full Text Available RTOS provides a number of services to an embedded system designs such as case management, memory management, and Resource Management to build a program. Choosing the best OS for an embedded system is based on the available OS for system designers and their previous knowledge and experience. This can cause an imbalance between the OS and embedded systems. RTOS performance analysis is critical in the design and integration of embedded software to ensure that limits the application meet at runtime. To select an appropriate operating system for an embedded system for a particular application, the OS services to be analyzed. These OS services are identified by parameters to establish performance metrics. Performance Metrics selected include context switching, Preemption time and interrupt latency. Performance Metrics are analyzed to choose the right OS for an embedded system for a particular application.

  4. Systems Architecture for a Nationwide Healthcare System.

    Science.gov (United States)

    Abin, Jorge; Nemeth, Horacio; Friedmann, Ignacio

    2015-01-01

    From a national level to give Internet technology support, the Nationwide Integrated Healthcare System in Uruguay requires a model of Information Systems Architecture. This system has multiple healthcare providers (public and private), and a strong component of supplementary services. Thus, the data processing system should have an architecture that considers this fact, while integrating the central services provided by the Ministry of Public Health. The national electronic health record, as well as other related data processing systems, should be based on this architecture. The architecture model described here conceptualizes a federated framework of electronic health record systems, according to the IHE affinity model, HL7 standards, local standards on interoperability and security, as well as technical advice provided by AGESIC. It is the outcome of the research done by AGESIC and Systems Integration Laboratory (LINS) on the development and use of the e-Government Platform since 2008, as well as the research done by the team Salud.uy since 2013.

  5. Autonomic Nervous System Disorders

    Science.gov (United States)

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  6. Calo trigger acquisition system

    CERN Multimedia

    Franchini, Matteo

    2016-01-01

    Calo trigger acquisition system - Evolution of the acquisition system from a multiple boards system (upper, orange cables) to a single board one (below, light blue cables) where all the channels are collected in a single board.

  7. Brain and Nervous System

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Brain and Nervous System KidsHealth > For Parents > Brain and Nervous System Print ... brain is quite the juggler. Anatomy of the Nervous System If you think of the brain as a ...

  8. for hybrid dynamical systems

    Directory of Open Access Journals (Sweden)

    Wassim M. Haddad

    2001-01-01

    Full Text Available In this paper we develop a unified dynamical systems framework for a general class of systems possessing left-continuous flows; that is, left-continuous dynamical systems. These systems are shown to generalize virtually all existing notions of dynamical systems and include hybrid, impulsive, and switching dynamical systems as special cases. Furthermore, we generalize dissipativity, passivity, and nonexpansivity theory to left-continuous dynamical systems. Specifically, the classical concepts of system storage functions and supply rates are extended to left-continuous dynamical systems providing a generalized hybrid system energy interpretation in terms of stored energy, dissipated energy over the continuous-time dynamics, and dissipated energy over the resetting events. Finally, the generalized dissipativity notions are used to develop general stability criteria for feedback interconnections of left-continuous dynamical systems. These results generalize the positivity and small gain theorems to the case of left-continuous, hybrid, and impulsive dynamical systems.

  9. Bridge Management Systems

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    In this paper bridge management systems are discussed with special emphasis on management systems for reinforced concrete bridges. Management systems for prestressed concrete bridges, steel bridges, or composite bridges can be developed in a similar way....

  10. Manned systems technology discipline

    Science.gov (United States)

    Bretoi, Remus

    1990-01-01

    Viewgraphs on manned systems technology discipline for Space Station Freedom are presented. Topics covered include: crew-systems interfaces and interactions; crew training; on-board systems maintenance and support; habitability and environment; and computational human factors.

  11. System Software 7 Macintosh

    CERN Multimedia

    1991-01-01

    System 7 is a single-user graphical user interface-based operating system for Macintosh computers and was part of the classic Mac OS line of operating systems. It was introduced on May 13, 1991, by Apple Computer. It succeeded System 6, and was the main Macintosh operating system until it was succeeded by Mac OS 8 in 1997. Features added with the System 7 release included virtual memory, personal file sharing, QuickTime, QuickDraw 3D, and an improved user interface. This is the first real major evolution of the Macintosh system, bringing a significant improvement in the user interface, improved stability and many new features such as the ability to use multiple applications at the same time. "System 7" is the last operating system name of the Macintosh that contains the word "system". Macintosh operating systems were later called "Mac OS" (for Macintosh Operating System).

  12. Game Information System

    CERN Document Server

    Warnars, Spits; Kingdom, United; 10.5121/ijcsit.2010.2310

    2010-01-01

    In this Information system age many organizations consider information system as their weapon to compete or gain competitive advantage or give the best services for non profit organizations. Game Information System as combining Information System and game is breakthrough to achieve organizations’ performance. The Game Information System will run the Information System with game and how game can be implemented to run the Information System. Game is not only for fun and entertainment, but will be a challenge to combine fun and entertainment with Information System. The Challenge to run the information system with entertainment, deliver the entertainment with information system all at once. Game information system can be implemented in many sectors as like the information system itself but in difference’s view. A view of game which people can joy and happy and do their transaction as a fun things.

  13. Central Nervous System Vasculitis

    Science.gov (United States)

    ... Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Central nervous system (CNS) vasculitis is inflammation of ... CNS (PACNS). What is the cause of CNS Vasculitis? How the vessels in the brain become inflamed ...

  14. Immune System Quiz

    Science.gov (United States)

    ... Know About Puberty Train Your Temper Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A How much do you know about your immune system? Find out by taking this quiz! About KidsHealth ...

  15. What Are Expert Systems?

    Science.gov (United States)

    d'Agapeyeff, A.

    1986-01-01

    Intended for potential business users, this paper describes the main characteristics of expert systems; discusses practical use considerations; presents a taxonomy of the systems; and reviews several expert system development projects in business and industry. (MBR)

  16. The Trinity System

    Energy Technology Data Exchange (ETDEWEB)

    Archer, Billy Joe [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Vigil, Benny Manuel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-01-13

    This paper describes the Trinity system, the first ASC Advanced Technology System (ATS-1). We describe the Trinity procurement timeline, the ASC computing strategy, the Trinity specific mission needs, and the Trinity system specifications.

  17. Marketing reporting system

    Directory of Open Access Journals (Sweden)

    Hanić Hasan M.

    2004-01-01

    Full Text Available The main components of a developed and good organized marketing information system are: internal reporting system, marketing reporting system, market research system and analytical marketing system. Marketing reporting system provides data and information about changes in business and micro marketing environment. This component of MIS ensures that marketing managers are up-to-date with what is going on, and to be informed about changes in company marketing environment.

  18. Marketing reporting system

    OpenAIRE

    Hanić Hasan M.

    2004-01-01

    The main components of a developed and good organized marketing information system are: internal reporting system, marketing reporting system, market research system and analytical marketing system. Marketing reporting system provides data and information about changes in business and micro marketing environment. This component of MIS ensures that marketing managers are up-to-date with what is going on, and to be informed about changes in company marketing environment.

  19. Small test SDHW systems

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian

    1999-01-01

    Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different.......Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different....

  20. Small test SDHW systems

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian

    1999-01-01

    Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different.......Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different....

  1. Law System in Japan

    OpenAIRE

    Andreea Lorena Ponaru

    2007-01-01

    This article attempts to present and explain the main features of the japanese law system. Japanese Law system was reformed during the domination of Tokugawa shogun family. In 1870, Foreign Governmental Systems Study Office was founded. By judicial sentences many french laws were introduced in Japanese law system. Roma-Tokyo-Berlin Alliance (1936) introduced a strong German influence in the law system. The Japanese judicial system has known five periods. In the first (1869-1888) were introduc...

  2. Battery systems engineering

    CERN Document Server

    Rahn, Christopher D

    2012-01-01

    A complete all-in-one reference on the important interdisciplinary topic of Battery Systems Engineering Focusing on the interdisciplinary area of battery systems engineering, this book provides the background, models, solution techniques, and systems theory that are necessary for the development of advanced battery management systems. It covers the topic from the perspective of basic electrochemistry as well as systems engineering topics and provides a basis for battery modeling for system engineering of electric and hybrid electric vehicle platforms. This original

  3. Airports Geographic Information System -

    Data.gov (United States)

    Department of Transportation — The Airports Geographic Information System maintains the airport and aeronautical data required to meet the demands of the Next Generation National Airspace System....

  4. Control system design method

    Science.gov (United States)

    Wilson, David G [Tijeras, NM; Robinett, III, Rush D.

    2012-02-21

    A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.

  5. Aeronautical Information System -

    Data.gov (United States)

    Department of Transportation — The Aeronautical Information System (AIS) is a leased weather automated system that provides a means of collecting and distributing aeronautical weather information...

  6. Cognitive Medical Multiagent Systems

    Directory of Open Access Journals (Sweden)

    Barna Iantovics

    2010-01-01

    Full Text Available The development of efficient and flexible agent-based medical diagnosis systems represents a recent research direction. Medical multiagent systems may improve the efficiency of traditionally developed medical computational systems, like the medical expert systems. In our previous researches, a novel cooperative medical diagnosis multiagent system called CMDS (Contract Net Based Medical Diagnosis System was proposed. CMDS system can solve flexibly a large variety of medical diagnosis problems. This paper analyses the increased intelligence of the CMDS system, which motivates its use for different medical problem’s solving.

  7. RECURSIVE SYSTEM IDENTIFICATION

    Institute of Scientific and Technical Information of China (English)

    Han-Fu Chen

    2009-01-01

    Most of existing methods in system identification with possible exception of those for linear systems are off-line in nature, and hence are nonrecursive.This paper demonstrates the recent progress in recursive system identification.The recursive identifi-cation algorithms are presented not only for linear systems (multivariate ARMAX systems) but also for nonlinear systems such as the Hammerstein and Wiener systems, and the non-linear ARX systems.The estimates generated by the algorithms are online updated and converge a.s.to the true values as time tends to infinity.

  8. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  9. Credit Management System

    Data.gov (United States)

    US Agency for International Development — Credit Management System. Outsourced Internet-based application. CMS stores and processes data related to USAID credit programs. The system provides information...

  10. Integrated Systems Health Management for Intelligent Systems

    Science.gov (United States)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. It is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this paper, concepts, procedures, and approaches are presented as a foundation for implementing an intelligent systems ]relevant ISHM capability. The capability stresses integration of DIaK from all elements of a system. Both ground-based (remote) and on-board ISHM capabilities are compared and contrasted. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  11. Epilogue: Systems Approaches and Systems Practice

    Science.gov (United States)

    Reynolds, Martin; Holwell, Sue

    Each of the five systems approaches discussed in this volume: system dynamics (SD), the viable systems model (VSM), strategic options development and analysis (SODA), soft systems methodology (SSM) and critical systems heuristics (CSH) has a pedigree. Not in the sense of the sometimes absurd spectacle of animals paraded at dog shows. Rather, their pedigree derives from their systems foundations, their capacity to evolve and their flexibility in use. None of the five approaches has developed out of use in restricted and controlled contexts of either low or high levels of complicatedness. Neither has any one of them evolved as a consequence of being applied only to situations with either presumed stakeholder agreement on purpose, or courteous disagreement amongst stakeholders, or stakeholder coercion. The compilation is not a celebration of abstract ‘methodologies', but of theoretically robust approaches that have a genuine pedigree in practice.

  12. Systems engineering for very large systems

    Science.gov (United States)

    Lewkowicz, Paul E.

    Very large integrated systems have always posed special problems for engineers. Whether they are power generation systems, computer networks or space vehicles, whenever there are multiple interfaces, complex technologies or just demanding customers, the challenges are unique. 'Systems engineering' has evolved as a discipline in order to meet these challenges by providing a structured, top-down design and development methodology for the engineer. This paper attempts to define the general class of problems requiring the complete systems engineering treatment and to show how systems engineering can be utilized to improve customer satisfaction and profit ability. Specifically, this work will focus on a design methodology for the largest of systems, not necessarily in terms of physical size, but in terms of complexity and interconnectivity.

  13. C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation

    Directory of Open Access Journals (Sweden)

    Christiane eAlbert-Weissenberger

    2014-09-01

    Full Text Available Traumatic brain injury (TBI induces a strong inflammatory response which includes blood-brain barrier damage, edema formation and infiltration of different immune cell subsets. More recently, microvascular thrombosis has been identified as another pathophysiological feature of TBI. The contact-kinin system represents an interface between inflammatory and thrombotic circuits and is activated in different neurological diseases. C1-Inhibitor counteracts activation of the contact-kinin system at multiple levels. We investigated the therapeutic potential of C1-Inhibitor in a model of TBI. Male and female C57BL/6 mice were subjected to cortical cryolesion and treated with C1-Inhibitor after 1 hour. Lesion volumes were assessed between day 1 and day 5 and blood-brain barrier damage, thrombus formation as well as the local inflammatory response were determined post TBI. Treatment of male mice with 15.0 IU C1-Inhibitor, but not 7.5 IU, 1 hour after cryolesion reduced lesion volumes by ~75% on day 1. This protective effect was preserved in female mice and at later stages of trauma. Mechanistically, C1-Inhibitor stabilized the blood-brain barrier and decreased the invasion of immune cells into the brain parenchyma. Moreover, C1-Inhibitor had strong antithrombotic effects. C1-Inhibitor represents a multifaceted antiinflammatory and antithrombotic compound that prevents traumatic neurodegeneration in clinically meaningful settings.

  14. Metadata Management System for Healthcare Information Systems

    OpenAIRE

    Patil, Ketan Shripat

    2011-01-01

    The Utah Department of Health (UDOH) uses multiple and diverse healthcare information systems for managing, maintaining, and sharing the health information. To keep track of the important details about these information systems such as the operational details, data semantics, data exchange standards, and personnel responsible for maintaining and managing it is a monumental task, with several limitations. This report describes the design and implementation of the Metadata Management System (MD...

  15. L-system fractals

    CERN Document Server

    Mishra, Jibitesh

    2007-01-01

    The book covers all the fundamental aspects of generating fractals through L-system. Also it provides insight to various researches in this area for generating fractals through L-system approach & estimating dimensions. Also it discusses various applications of L-system fractals. Key Features: - Fractals generated from L-System including hybrid fractals - Dimension calculation for L-system fractals - Images & codes for L-system fractals - Research directions in the area of L-system fractals - Usage of various freely downloadable tools in this area - Fractals generated from L-System including hybrid fractals- Dimension calculation for L-system fractals- Images & codes for L-system fractals- Research directions in the area of L-system fractals- Usage of various freely downloadable tools in this area

  16. Distributed computer control systems

    Energy Technology Data Exchange (ETDEWEB)

    Suski, G.J.

    1986-01-01

    This book focuses on recent advances in the theory, applications and techniques for distributed computer control systems. Contents (partial): Real-time distributed computer control in a flexible manufacturing system. Semantics and implementation problems of channels in a DCCS specification. Broadcast protocols in distributed computer control systems. Design considerations of distributed control architecture for a thermal power plant. The conic toolset for building distributed systems. Network management issues in distributed control systems. Interprocessor communication system architecture in a distributed control system environment. Uni-level homogenous distributed computer control system and optimal system design. A-nets for DCCS design. A methodology for the specification and design of fault tolerant real time systems. An integrated computer control system - architecture design, engineering methodology and practical experience.

  17. Forming different planetary systems

    Institute of Scientific and Technical Information of China (English)

    Ji-Lin Zhou; Ji-Wei Xie; Hui-Gen Liu; Hui Zhang; Yi-Sui Sun

    2012-01-01

    With the increasing number of detected exoplanet samples,the statistical properties of planetary systems have become much clearer.In this review,we summarize the major statistical results that have been revealed mainly by radial velocity and transiting observations,and try to interpret them within the scope of the classical core-accretion scenario of planet formation,especially in the formation of different orbital architectures for planetary systems around main sequence stars.Based on the different possible formation routes for different planet systems,we tentatively classify them into three major catalogs:hot Jupiter systems,standard systems and distant giant planet systems.The standard systems can be further categorized into three sub-types under different circumstances:solar-like systems,hot Super-Earth systems,and subgiant planet systems.We also review the theory of planet detection and formation in binary systems as well as planets in star clusters.

  18. Site systems engineering: Systems engineering management plan

    Energy Technology Data Exchange (ETDEWEB)

    Grygiel, M.L. [Westinghouse Hanford Co., Richland, WA (United States)

    1996-05-03

    The Site Systems Engineering Management Plan (SEMP) is the Westinghouse Hanford Company (WHC) implementation document for the Hanford Site Systems Engineering Policy, (RLPD 430.1) and Systems Engineering Criteria Document and Implementing Directive, (RLID 430.1). These documents define the US Department of Energy (DOE), Richland Operations Office (RL) processes and products to be used at Hanford to implement the systems engineering process at the site level. This SEMP describes the products being provided by the site systems engineering activity in fiscal year (FY) 1996 and the associated schedule. It also includes the procedural approach being taken by the site level systems engineering activity in the development of these products and the intended uses for the products in the integrated planning process in response to the DOE policy and implementing directives. The scope of the systems engineering process is to define a set of activities and products to be used at the site level during FY 1996 or until the successful Project Hanford Management Contractor (PHMC) is onsite as a result of contract award from Request For Proposal DE-RP06-96RL13200. Following installation of the new contractor, a long-term set of systems engineering procedures and products will be defined for management of the Hanford Project. The extent to which each project applies the systems engineering process and the specific tools used are determined by the project`s management.

  19. Hot Spot Removal System: System description

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System`s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section.

  20. SYSTEMS APPROACH FOR CONTEMPORARY COMPLEX TOURISM SYSTEMS

    Directory of Open Access Journals (Sweden)

    Tadeja Jere Jakulin

    2016-09-01

    Full Text Available Systems approach represents thinking outside the box and is connected to the transformation of common linear approach and thinking. Western society followed rules of classical western science, which form many centuries took analysis as mainstream of thinking and researching. One can find perfect and logical explanation for this. In the past, classical science researched matter and reached optimal results with analysis and analytical thinking. Nowadays more and more scientists research intangible world around matter and cooperate with prevailed, fastest growing service industry such as tourism. Following paper presents systems approach in tourism, which defines wideness, co-dependency among tourism system elements, and "big picture" point of view. In a frame of systems methodology, we will show the importance of systems approach in order to understand complexity in the area of tourism. At once an excellent example of the analytical approach will be shown in so called "the tip of the iceberg" theory, where events represent analytical thinking and structure or base of the iceberg represents systems approach. Complexity of the tourism systems will be explained and a model of a common tourism system developed. We claim that the analysis, in the past, caused technological progress; it caused the development of western science, which we now know it. It led to the discoveries but for dealing with contemporary complex challenges is not sufficient. Today a systems approach is suitable enough for dealing with complex question in the area of tourism and of course in global society.

  1. Novel central nervous system drug delivery systems.

    Science.gov (United States)

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  2. Recommender Systems for Social Tagging Systems

    CERN Document Server

    Balby Marinho, Leandro

    2012-01-01

    Social Tagging Systems are web applications in which users upload resources (e.g., bookmarks, videos, photos, etc.) and annotate it with a list of freely chosen keywords called tags. This is a grassroots approach to organize a site and help users to find the resources they are interested in. Social tagging systems are open and inherently social; features that have been proven to encourage participation. However, with the large popularity of these systems and the increasing amount of user-contributed content, information overload rapidly becomes an issue. Recommender Systems are well known appl

  3. Power system protection 2 systems and methods

    CERN Document Server

    1995-01-01

    The worldwide growth in demand for electricity has forced the pace of developments in electrical power system design to meet consumer needs for reliable, secure and cheap supplies. Power system protection, as a technology essential to high quality supply, is widely recognised as a specialism of growing and often critical importance, in which power system needs and technological progress have combined to result in rapid developments in policy and practice in recent years. In the United Kingdom, the need for appropriate training in power system protection was recognised in the early 1960s with t

  4. STEP electronic system design

    Science.gov (United States)

    Couch, R. H.; Johnson, J. W.

    1984-01-01

    The STEP electronic system design is discussed. The purpose of the design is outlined. The electronic system design is summarized and it is found that: an effective conceptual system design is developed; the design represents a unique set of capabilities; makes efficient use of available orbiter resources; the system capabilities exceed identified potential experiment needs.

  5. Nonlinear Hamiltonian systems

    DEFF Research Database (Denmark)

    Jørgensen, Michael Finn

    1995-01-01

    It is generally very difficult to solve nonlinear systems, and such systems often possess chaotic solutions. In the rare event that a system is completely solvable, it is said to integrable. Such systems never have chaotic solutions. Using the Inverse Scattering Transform Method (ISTM) two...

  6. Product Service Systems

    DEFF Research Database (Denmark)

    Departing from Product Development models based on physical artefacts. Moving towards integrated Product Development and System Operations models suited Product/Service-systems......Departing from Product Development models based on physical artefacts. Moving towards integrated Product Development and System Operations models suited Product/Service-systems...

  7. Medical imaging systems

    Science.gov (United States)

    Frangioni, John V

    2013-06-25

    A medical imaging system provides simultaneous rendering of visible light and diagnostic or functional images. The system may be portable, and may include adapters for connecting various light sources and cameras in open surgical environments or laparascopic or endoscopic environments. A user interface provides control over the functionality of the integrated imaging system. In one embodiment, the system provides a tool for surgical pathology.

  8. Measuring Systemic Risk

    DEFF Research Database (Denmark)

    Acharya, Viral V.; Heje Pedersen, Lasse; Philippon, Thomas

    We present a simple model of systemic risk and we show that each financial institution's contribution to systemic risk can be measured as its systemic expected shortfall (SES), i.e., its propensity to be undercapitalized when the system as a whole is undercapitalized. SES increases...

  9. Universal Index System

    Science.gov (United States)

    Kelley, Steve; Roussopoulos, Nick; Sellis, Timos; Wallace, Sarah

    1993-01-01

    The Universal Index System (UIS) is an index management system that uses a uniform interface to solve the heterogeneity problem among database management systems. UIS provides an easy-to-use common interface to access all underlying data, but also allows different underlying database management systems, storage representations, and access methods.

  10. Hybrid intelligent engineering systems

    CERN Document Server

    Jain, L C; Adelaide, Australia University of

    1997-01-01

    This book on hybrid intelligent engineering systems is unique, in the sense that it presents the integration of expert systems, neural networks, fuzzy systems, genetic algorithms, and chaos engineering. It shows that these new techniques enhance the capabilities of one another. A number of hybrid systems for solving engineering problems are presented.

  11. Central Dental Evacuation Systems.

    Science.gov (United States)

    1982-05-01

    20 High-Vacuum Oral Evacuation System (HIVAC) for Oral Surgery, Periodontics, and Endodontics Treatment Rooms..................... 20...handpiece. Inlets to this system are required throughout the dental facility for all disciplines of patient treatment where coolant and irrigation liquids...System (HIVAC) for Oral Surgery, Periodontics, and Endodontics Treatment Rooms The HIVAC system is designed to build and sustain high vacuum pressures

  12. CDMA systems capacity engineering

    CERN Document Server

    Kim, Kiseon

    2004-01-01

    This new hands-on resource tackles capacity planning and engineering issues that are crucial to optimizing wireless communication systems performance. Going beyond the system physical level and investigating CDMA system capacity at the service level, this volume is the single-source for engineering and analyzing systems capacity and resources.

  13. System Performance and Testing

    NARCIS (Netherlands)

    Frei, U.; Oversloot, H.

    2004-01-01

    This chapter compares and contrasts the system performance of two widely used solar thermal systems using testing and simulation programs. Solar thermal systems are used in many countries for heating domestically used water. In addition to the simple thermosiphon systems, better designed pumped syst

  14. Expert Systems: An Overview.

    Science.gov (United States)

    Adiga, Sadashiv

    1984-01-01

    Discusses: (1) the architecture of expert systems; (2) features that distinguish expert systems from conventional programs; (3) conditions necessary to select a particular application for the development of successful expert systems; (4) issues to be resolved when building expert systems; and (5) limitations. Examples of selected expert systems…

  15. Information Systems Security Audit

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2007-12-01

    Full Text Available The article covers:Defining an information system; benefits obtained by introducing new information technologies; IT management;Defining prerequisites, analysis, design, implementation of IS; Information security management system; aspects regarding IS security policy; Conceptual model of a security system; Auditing information security systems and network infrastructure security.

  16. ERP–systems

    OpenAIRE

    Shustova I.

    2016-01-01

    In this work, we analyzed the existing ERP–systems of foreign and domestic manufacturers. Popular ERP–systems in the Republic of Belarus were considered. The leading ERP-systems in the domestic market and their features were described in detail. Finally, we described the steps that must be taken to select the most suitable ERP-system for a particular company.

  17. Type Systems for Bigraphs

    DEFF Research Database (Denmark)

    Elsborg, Ebbe; Hildebrandt, Thomas; Sangiorgi, Davide

    of controls and a set of reaction rules, collectively a bigraphical reactive system (BRS). Possible advantages of developing bigraphical type systems include: a deeper understanding of a type system itself and its properties; transfer of the type systems to the concrete family of calculi that the BRS models...

  18. Product Service Systems

    DEFF Research Database (Denmark)

    Departing from Product Development models based on physical artefacts. Moving towards integrated Product Development and System Operations models suited Product/Service-systems......Departing from Product Development models based on physical artefacts. Moving towards integrated Product Development and System Operations models suited Product/Service-systems...

  19. Information Systems Security Audit

    OpenAIRE

    Gheorghe Popescu; Veronica Adriana Popescu; Cristina Raluca Popescu

    2007-01-01

    The article covers:Defining an information system; benefits obtained by introducing new information technologies; IT management;Defining prerequisites, analysis, design, implementation of IS; Information security management system; aspects regarding IS security policy; Conceptual model of a security system; Auditing information security systems and network infrastructure security.

  20. ERP–systems

    OpenAIRE

    Shustova I.

    2016-01-01

    In this work, we analyzed the existing ERP–systems of foreign and domestic manufacturers. Popular ERP–systems in the Republic of Belarus were considered. The leading ERP-systems in the domestic market and their features were described in detail. Finally, we described the steps that must be taken to select the most suitable ERP-system for a particular company.

  1. On generalized Volterra systems

    Science.gov (United States)

    Charalambides, S. A.; Damianou, P. A.; Evripidou, C. A.

    2015-01-01

    We construct a large family of evidently integrable Hamiltonian systems which are generalizations of the KM system. The algorithm uses the root system of a complex simple Lie algebra. The Hamiltonian vector field is homogeneous cubic but in a number of cases a simple change of variables transforms such a system to a quadratic Lotka-Volterra system. We present in detail all such systems in the cases of A3, A4 and we also give some examples from higher dimensions. We classify all possible Lotka-Volterra systems that arise via this algorithm in the An case.

  2. Multiobjective Collaborative Optimization of Systems of Systems

    Science.gov (United States)

    2005-06-01

    operationally independent. (System-ysem 1)..y Design ,I ’"esignReqm ts ... .em (Sy stem 1) S stems F S Funcion Overlap Reqmts...te m...284. Maier, M.W. & Rechtin, E. (2002). The art of systems architecting. (2nd ed.). Boca Raton, FL: CRC Press LLC. Marglin, S. (1967). Public

  3. The Solar System as an Exoplanetary System

    CERN Document Server

    Martin, Rebecca G

    2015-01-01

    With the availability of considerably more data, we revisit the question of how special our Solar System is, compared to observed exoplanetary systems. To this goal, we employ a mathematical transformation that allows for a meaningful, statistical comparison. We find that the masses and densities of the giant planets in our Solar System are very typical, as is the age of the Solar System. While the orbital location of Jupiter is somewhat of an outlier, this is most likely due to strong selection effects towards short-period planets. The eccentricities of the planets in our Solar System are relatively small compared to those in observed exosolar systems, but still consistent with the expectations for an 8-planet system (and could, in addition, reflect a selection bias towards high-eccentricity planets). The two characteristics of the Solar System that we find to be most special are the lack of super-Earths with orbital periods of days to months and the general lack of planets inside of the orbital radius of Me...

  4. Variable Structure Systems and Systems Zeros

    OpenAIRE

    El-Ghezawi, O.M.E.; S. A. Billings; Zinober, A.S.I.

    1981-01-01

    The analysis of variable structure systems in the sliding mode yields the concept of equivalent control which leads naturally to a new method for determining the zeros and zero directions of linear multivariable systems. The analysis presented is conceptually easy and computationally attractive.

  5. Applications of membrane systems in distributed systems

    Institute of Scientific and Technical Information of China (English)

    Aneta Binder; Rudolf Freund; Georg Lojka; Marion Oswald

    2007-01-01

    Based on the biological model of cell-to-cell communication proposed by A. Rustom et al. (Science, 2004, 303: 1007-1010), we investigate the possibilities to apply P systems with dynamic channels transporting membrane vesicles for describing processes in distributed systems.

  6. Performance, Performance System, and High Performance System

    Science.gov (United States)

    Jang, Hwan Young

    2009-01-01

    This article proposes needed transitions in the field of human performance technology. The following three transitions are discussed: transitioning from training to performance, transitioning from performance to performance system, and transitioning from learning organization to high performance system. A proposed framework that comprises…

  7. [Universal coaxial anesthetic system].

    Science.gov (United States)

    Ungerer, M J; le Roux, F P

    1978-02-25

    A true universal co-axial anaesthetic system has been designed. This system may be used either as a Mapleson A circuit during spontaneous ventilation or as a Mapleson D circuit during controlled ventilation. Conversion to either system may be conveniently carried out by interchanging the pop-off valve and fresh gas inlet, without disconnecting the system from the patient. Resistance to flow of both tubes has been measured and was found to be within acceptable limits. The efficiency of this system in a Mapleson A arrangement was compared with that of a conventional Magill circuit during spontaneous breathing in 2 conscious volunteers. It was shown that no significant difference exists between these systems eith regard to rebreathing, and that the universal co-axial system may be used as efficiently and economically as the Magill circuit during spontaneous ventilation. The co-axial system can be easily connected to a circle system, combining the advantages of the two systems.

  8. Dynamical system synchronization

    CERN Document Server

    Luo, Albert C J

    2013-01-01

    Dynamical System Synchronization (DSS) meticulously presents for the first time the theory of dynamical systems synchronization based on the local singularity theory of discontinuous dynamical systems. The book details the sufficient and necessary conditions for dynamical systems synchronizations, through extensive mathematical expression. Techniques for engineering implementation of DSS are clearly presented compared with the existing techniques.  This book also:  Presents novel concepts and methods for dynamical system synchronization Extends beyond the Lyapunov theory for dynamical system synchronization Introduces companion and synchronization of discrete dynamical systems Includes local singularity theory for discontinuous dynamical systems Covers the invariant domains of synchronization Features more than 75 illustrations Dynamical System Synchronization is an ideal book for those interested in better understanding new concepts and methodology for dynamical system synchronization, local singularity...

  9. Intrusion Detection System: Security Monitoring System

    Directory of Open Access Journals (Sweden)

    ShabnamNoorani,

    2015-10-01

    Full Text Available An intrusion detection system (IDS is an ad hoc security solution to protect flawed computer systems. It works like a burglar alarm that goes off if someone tampers with or manages to get past other security mechanisms such as authentication mechanisms and firewalls. An Intrusion Detection System (IDS is a device or a software application that monitors network or system activities for malicious activities or policy violations and produces reports to a management station.Intrusion Detection System (IDS has been used as a vital instrument in defending the network from this malicious or abnormal activity..In this paper we are comparing host based and network based IDS and various types of attacks possible on IDS.

  10. Measuring Systemic Risk

    DEFF Research Database (Denmark)

    Acharya, Viral V.; Heje Pedersen, Lasse; Philippon, Thomas

    2017-01-01

    We present an economic model of systemic risk in which undercapitalization of the financial sector as a whole is assumed to harm the real economy, leading to a systemic risk externality. Each financial institution’s contribution to systemic risk can be measured as its systemic expected shortfall...... of components of SES to predict emerging systemic risk during the financial crisis of 2007–2009....

  11. Photovoltaic systems and applications

    Energy Technology Data Exchange (ETDEWEB)

    1982-01-01

    Abstracts are given of presentations given at a project review meeting held at Albuquerque, NM. The proceedings cover the past accomplishments and current activities of the Photovoltaic Systems Research, Balance-of-System Technology Development and System Application Experiments Projects at Sandia National Laboratories. The status of intermediate system application experiments and residential system analysis is emphasized. Some discussion of the future of the Photovoltaic Program in general, and the Sandia projects in particular is also presented.

  12. HYBRID VEHICLE CONTROL SYSTEM

    Directory of Open Access Journals (Sweden)

    V. Dvadnenko

    2016-06-01

    Full Text Available The hybrid vehicle control system includes a start–stop system for an internal combustion engine. The system works in a hybrid mode and normal vehicle operation. To simplify the start–stop system, there were user new possibilities of a hybrid car, which appeared after the conversion. Results of the circuit design of the proposed system of basic blocks are analyzed.

  13. Systems Theory and Systems Approach to Leadership

    Directory of Open Access Journals (Sweden)

    Dr.Sc. Berim Ramosaj

    2014-06-01

    Full Text Available Systems theory is product of the efforts of many researchers to create an intermediate field of coexistence of all sciences. If not for anything else, because of the magnitude that the use of systemic thinking and systemic approach has taken, it has become undisputed among the theories. Systems theory not only provides a glossary of terms with which researchers from different fields can be understood, but provides a framework for the presentation and interpretation of phenomena and realities. This paper addresses a systematic approach to leadership, as an attempt to dredge leadership and systems theory literature to find the meeting point. Systems approach is not an approach to leadership in terms of a manner of leader’s work, but it’s the leader's determination to factorize in his leadership the external environment and relationships with and among elements. Leader without followers is unable to exercise his leadership and to ensure their conviction he should provide a system, a structure, a purpose, despite the alternative chaos. Systems approach clarifies the thought on the complexity and dynamism of the environment and provides a framework for building ideas. If the general system theory is the skeleton of science (Boulding: 1956, this article aims to replenish it with leadership muscles by prominent authors who have written on systems theory and leadership, as well as through original ideas. In this work analytical methods were used (by analyzing approaches individually as well as synthetic methods (by assaying individual approaches in context of entirety. The work is a critical review of literature as well as a deductive analysis mingled with models proposed by authors through inductive analysis. Meta-analysis has been used to dissect the interaction and interdependence between leadership approaches.

  14. A distribution management system

    Energy Technology Data Exchange (ETDEWEB)

    Verho, P.; Jaerventausta, P.; Kaerenlampi, M.; Paulasaari, H. [Tampere Univ. of Technology (Finland); Partanen, J. [Lappeenranta Univ. of Technology (Finland)

    1996-12-31

    The development of new distribution automation applications is considerably wide nowadays. One of the most interesting areas is the development of a distribution management system (DMS) as an expansion of the traditional SCADA system. At the power transmission level such a system is called an energy management system (EMS). The idea of these expansions is to provide supporting tools for control center operators in system analysis and operation planning. The needed data for new applications is mainly available in some existing systems. Thus the computer systems of utilities must be integrated. The main data source for the new applications in the control center are the AM/FM/GIS (i.e. the network database system), the SCADA, and the customer information system (CIS). The new functions can be embedded in some existing computer system. This means a strong dependency on the vendor of the existing system. An alternative strategy is to develop an independent system which is integrated with other computer systems using well-defined interfaces. The latter approach makes it possible to use the new applications in various computer environments, having only a weak dependency on the vendors of the other systems. In the research project this alternative is preferred and used in developing an independent distribution management system

  15. A System of Systems Approach to the EU Energy System

    Science.gov (United States)

    Jess, Tom; Madani, Kaveh; Mahlooji, Maral; Ristic, Bora

    2016-04-01

    Around the world, measures to prevent dangerous climate change are being adopted and may change energy systems fundamentally. The European Union (EU) is committed to reducing greenhouse gas emission by 20% by 2020 and by 80-95% by 2050. In order to achieve this, EU member states aim to increase the share of renewables in the energy mix to 20% by 2020. This commitment comes as part of a series of other aims, principles, and policies to reform the EU's energy system. Cost-efficiency in the emissions reductions measures as well as strategic goals under the Resource Efficient Europe flagship initiative which would include a more prudent approach to other natural resources such as water and land. Using the "System of Systems Approach", as from Hadian and Madani (2015), energy sources' Relative Aggregate Footprints (RAF) in the EU are evaluated. RAF aggregates across four criteria: carbon footprint, water footprint, land footprint, and economic cost. The four criteria are weighted by resource availability across the EU and for each Member State. This provides an evaluation of the overall resource use efficiency of the EU's energy portfolio and gives insight into the differences in the desirability of energy sources across Member States. Broadly, nuclear, onshore wind, and geothermal are most desirable under equal criteria weights and EU average weighting introduces only small changes in the relative performance of only few technologies. The member state specific weightings show that most countries have similar energy technology preferences. However, the UK deviates most strongly from the average, with an even stronger preference for nuclear and coal. Sweden, Malta and Finland also deviate from the typical preferences indicating the complexity in play in reforming the EU energy system. Reference Hadian S, Madani K (2015) A System of Systems Approach to Energy Sustainability Assessment: Are All Renewables Really Green? Ecological Indicators, 52, 194-206.

  16. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  17. Intelligent systems technology infrastructure for integrated systems

    Science.gov (United States)

    Lum, Henry

    1991-01-01

    A system infrastructure must be properly designed and integrated from the conceptual development phase to accommodate evolutionary intelligent technologies. Several technology development activities were identified that may have application to rendezvous and capture systems. Optical correlators in conjunction with fuzzy logic control might be used for the identification, tracking, and capture of either cooperative or non-cooperative targets without the intensive computational requirements associated with vision processing. A hybrid digital/analog system was developed and tested with a robotic arm. An aircraft refueling application demonstration is planned within two years. Initially this demonstration will be ground based with a follow-on air based demonstration. System dependability measurement and modeling techniques are being developed for fault management applications. This involves usage of incremental solution/evaluation techniques and modularized systems to facilitate reuse and to take advantage of natural partitions in system models. Though not yet commercially available and currently subject to accuracy limitations, technology is being developed to perform optical matrix operations to enhance computational speed. Optical terrain recognition using camera image sequencing processed with optical correlators is being developed to determine position and velocity in support of lander guidance. The system is planned for testing in conjunction with Dryden Flight Research Facility. Advanced architecture technology is defining open architecture design constraints, test bed concepts (processors, multiple hardware/software and multi-dimensional user support, knowledge/tool sharing infrastructure), and software engineering interface issues.

  18. Does zaltoprofen antagonize the bradykinin receptors?

    Science.gov (United States)

    Bawolak, Marie-Thérèse; Marceau, François

    2007-05-03

    Zaltoprofen is a nonsteroidal antiinflammatory drug that has been proposed to inhibit with some selectivity the nociception mediated by the bradykinin (BK) B(2) receptor. In order to test the predictive power of this claim, we applied the drug to vascular smooth muscle assays previously found useful to characterize B(2) receptor antagonists (contractility, human isolated umbilical vein) or B(1) receptor antagonists (contraction, rabbit aorta; relaxation, rabbit mesenteric artery). Zaltoprofen (up to 30 microM) failed to antagonize BK or des-Arg(9)-BK-induced contraction in the umbilical vein and aorta, respectively. The drug (1 microM) abated des-Arg(9)-BK-induced, prostaglandin-mediated relaxation of the precontracted mesenteric artery, consistent with its known activity as a cyclooxygenase (COX) inhibitor. However, zaltoprofen (10 microM) did not inhibit kinin-stimulated phospholipase A(2) activity in HEK 293 cells expressing recombinant forms of the rabbit B(1) or B(2) receptors. Nonpeptide antagonists of either receptor subtype were active in this respect. The results do not support that zaltoprofen, a COX inhibitor, antagonizes kinin receptors or influences their signaling with selectivity in the tested systems.

  19. Micro Information Systems

    DEFF Research Database (Denmark)

    Ulslev Pedersen, Rasmus; Kühn Pedersen, Mogens

    2014-01-01

    such as medical and manufacturing. These new sensor applications have implications for information systems (IS) and, the authors visualize this new class of information systems as fractals growing from an established class of systems; namely that of information systems (IS). The identified applications...... and implications are used as an empirical basis for creating a model for these small new information systems. Such sensor systems are called embedded systems in the technical sciences, and the authors want to couple it with general IS. They call the merger of these two important research areas (IS and embedded...... systems) for micro information systems (micro-IS). It is intended as a new research field within IS research. An initial framework model is established, which seeks to capture both the possibilities and constraints of this new paradigm, while looking simultaneously at the fundamental IS and ICT aspects...

  20. Rover waste assay system

    Energy Technology Data Exchange (ETDEWEB)

    Akers, D.W.; Stoots, C.M.; Kraft, N.C.; Marts, D.J. [Idaho National Engineering Lab., Idaho Falls, ID (United States)

    1997-11-01

    The Rover Waste Assay System (RWAS) is a nondestructive assay system designed for the rapid assay of highly-enriched {sup 235}U contaminated piping, tank sections, and debris from the Rover nuclear rocket fuel processing facility at the Idaho Chemical Processing Plant. A scanning system translates a NaI(Tl) detector/collimator system over the structural components where both relative and calibrated measurements for {sup 137}Cs are made. Uranium-235 concentrations are in operation and is sufficiently automated that most functions are performed by the computer system. These functions include system calibration, problem identification, collimator control, data analysis, and reporting. Calibration of the system was done through a combination of measurements on calibration standards and benchmarked modeling. A description of the system is presented along with the methods and uncertainties associated with the calibration and analysis of the system for components from the Rover facility. 4 refs., 2 figs., 4 tabs.