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Sample records for brain natruretic peptide

  1. The Relationship Between Heart Rate Recovery and Brain Natruretic Peptide in Patients With Chest Discomfort

    OpenAIRE

    Lee, Jae Eun; Kim, Bum Soo; Park, Wan; Huh, Jung Kwon; Kim, Byung Jin; Sung, Ki Chul; Kang, Jin Ho; Lee, Man Ho; Park, Jung Ro

    2010-01-01

    Background and Objectives The correlation between brain natruretic peptide (BNP) level and cardiac autonomic function has been studied in type 2 diabetic patients. However, there is limited data from patients with normal systolic function. We evaluated the association between heart rate recovery (HRR) representing autonomic dysfunction and three plasma BNP levels: pre-exercise, post-exercise, and change during exercise in patients with normal systolic function. Subjects and Methods Subjects i...

  2. Antimicrobial peptides in the brain.

    Science.gov (United States)

    Su, Yanhua; Zhang, Kai; Schluesener, Hermann J

    2010-10-01

    Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune system of many species. The brain is an immunologically privileged organ but can produce a robust immune response against pathogens and cell debris, promoting rapid and efficient clearance. AMPs may be critically involved in the innate immune system of the brain. Though the mechanisms of AMPs' action in the brain still need further elucidation, many studies have shown that AMPs are multifunctional molecules in the brain. In addition to antimicrobial action, they take part in congenital and adaptive immune reactions (immunoregulation), function as signaling molecules in tissue repair, inflammation and other important processes through different mechanisms, and they might, in addition, become diagnostic markers of brain disease.

  3. Brain natriuretic peptide: Diagnostic potential in dogs

    Directory of Open Access Journals (Sweden)

    Spasojević-Kosić Ljubica

    2009-01-01

    Full Text Available The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .

  4. Peptide-Mediated Blood-Brain Barrier Transport of Polymersomes

    NARCIS (Netherlands)

    Georgieva, J.V.; Brinkhuis, R.P.; Stojanov, K.; Weijers, C.A.G.M.; Zuilhof, H.; Rutjes, F.P.J.T.; Hoekstra, D.; Hest, van J.C.M.; Zuhorn, I.S.

    2012-01-01

    A polymeric nanocarrier: Polymersomes tagged with a dodecamer peptide that recognizes gangliosides GM1 and GT1b are shown to cross the blood–brain barrier, both in an in vitro model and in vivo (see picture). The combination of polymeric vesicles with a small GM1-binding peptide and GM1/GT1b ganglio

  5. Brain natriuretic peptide measurement in pulmonary medicine.

    Science.gov (United States)

    Salerno, Daniel; Marik, Paul E

    2011-12-01

    Serum levels of natriuretic peptides are well established as important biomarkers in patients with cardiac disease. Less attention has been placed on the role of natriuretic peptides in patients with pulmonary conditions. In several well-defined groups of patients with pulmonary disease natriuretic peptides provide the clinician with clinically valuable information. A limitation of the interpretation of natriuretic peptides in pulmonary disease is the confounding effect of concurrent conditions such as heart failure, hypoxia, sepsis and renal failure. The present paper reviews the role of natriuretic peptides for diagnosis, risk stratification and prognosis of several pulmonary disorders.

  6. Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier.

    Science.gov (United States)

    Wynendaele, Evelien; Verbeke, Frederick; Stalmans, Sofie; Gevaert, Bert; Janssens, Yorick; Van De Wiele, Christophe; Peremans, Kathelijne; Burvenich, Christian; De Spiegeleer, Bart

    2015-01-01

    Bacteria communicate with each other by the use of signaling molecules, a process called 'quorum sensing'. One group of quorum sensing molecules includes the oligopeptides, which are mainly produced by Gram-positive bacteria. Recently, these quorum sensing peptides were found to biologically influence mammalian cells, promoting i.a. metastasis of cancer cells. Moreover, it was found that bacteria can influence different central nervous system related disorders as well, e.g. anxiety, depression and autism. Research currently focuses on the role of bacterial metabolites in this bacteria-brain interaction, with the role of the quorum sensing peptides not yet known. Here, three chemically diverse quorum sensing peptides were investigated for their brain influx (multiple time regression technique) and efflux properties in an in vivo mouse model (ICR-CD-1) to determine blood-brain transfer properties: PhrCACET1 demonstrated comparatively a very high initial influx into the mouse brain (Kin = 20.87 μl/(g×min)), while brain penetrabilities of BIP-2 and PhrANTH2 were found to be low (Kin = 2.68 μl/(g×min)) and very low (Kin = 0.18 μl/(g×min)), respectively. All three quorum sensing peptides were metabolically stable in plasma (in vitro) during the experimental time frame and no significant brain efflux was observed. Initial tissue distribution data showed remarkably high liver accumulation of BIP-2 as well. Our results thus support the potential role of some quorum sensing peptides in different neurological disorders, thereby enlarging our knowledge about the microbiome-brain axis.

  7. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Gøtze, J P; Fuglsang, S;

    2003-01-01

    BACKGROUND AND AIMS: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers...

  8. Brain natriuretic peptide and optimal management of heart failure

    Institute of Scientific and Technical Information of China (English)

    LI Nan; WANG Jian-an

    2005-01-01

    Aside from the important role of brain natriuretic peptide (BNP) in diagnosis, and differential diagnosis of heart failure, this biological peptide has proved to be an independent surrogate marker of rehospitalization and death of the fatal disease.Several randomized clinical trials demonstrated that drugs such as beta blocker, angiotensin converting enzyme inhibitor, spironolactone and amiodarone have beneficial effects in decreasing circulating BNP level during the management of chronic heart failure. The optimization of clinical decision-making appeals for a representative surrogate marker for heart failure prognosis. The serial point-of-care assessments of BNP concentration provide a therapeutic goal of clinical multi-therapy and an objective guidance for optimal treatment of heart failure. Nevertheless new questions and problems in this area remain to be clarified. On the basis of current research advances, this article gives an overview of BNP peptide and its property and role in the management of heart failure.

  9. Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Chelsea A Vadnie

    2014-09-01

    Full Text Available Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use disorders (AUD. In this review, we discuss the effects of several gut-brain peptides on alcohol-related behaviors and the potential mechanisms by which these gut-brain peptides may interfere with alcohol-induced changes in corticostriatal-limbic circuitry. This review provides a summary of current knowledge on gut-brain peptides focusing on five peptides: neurotensin, glucagon-like peptide 1, ghrelin, substance P, and neuropeptide Y. Our review will be helpful to develop novel therapeutic targets for AUD.

  10. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    Directory of Open Access Journals (Sweden)

    Essam M Abdelalim

    2016-12-01

    Full Text Available Brain natriuretic peptide (BNP exerts its functions through natriuretic peptide receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using RT-PCR and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and DRG. BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the dorsal horn of the spinal cord and in the neurons of the intermediate column and ventral horn. Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I-II labeled with calcitonin gene-related peptide (CGRP, suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase in the motor neurons of the ventral horn. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NPR-A and/or NPR-B in the DRG and spinal cord.

  11. Effect of Professional Exercises on Brain Natriuretic Peptide

    Directory of Open Access Journals (Sweden)

    MA Babaee Beigi

    2009-12-01

    Full Text Available Background: Brain natriuretic peptide (BNP reflects myocardial wall stress. BNP activities are similar to those of atrial natriuretic peptide, including diuresis, natriuresis, hypotension and smooth muscle relaxation as well as ability to inhibit the rennin aldosterone system. It is mainly produced and released into the circulation by the ventricle in response to increased ventricular wall pressure or stretching. Therefore, BNP can be served as a marker of left ventricular dysfunction. The aim of this study was to investigate effect of various professional exercises on plasma BNP levels.Methods: We enrolled 20 consecutive healthy professional athletic males from different sporting disciplines including 5 football players, 5 volleyball players, 5 bodybuilders and 5 water- polo players. Plasma BNP samples were taken immediately before and 1 hour after exercise.Results: Plasma BNP level was significantly increased after exercise (30.01 ± 23.46 vs. 16.72 ± 10.86 pg/ml; P= 0.042. The highest increase in BNP level was found among volleyball players (mean values: 19.12 to 43.38 pg/ml; 126.3% increase after volleyball compared to other exercises. Conclusion: Exercise can increase plasma BNP levels, particularly among volleyball players.

  12. Brain natriuretic peptide concentrations after aneurysmal subarachnoid hemorrhage : relationship with hypovolemia and hyponatremia

    NARCIS (Netherlands)

    Dorhout Mees, Sanne M; Hoff, Reinier G; Rinkel, Gabriel J E; Algra, Ale; van den Bergh, Walter M

    2011-01-01

    BACKGROUND: Hyponatremia and hypovolemia occur often after aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor outcome. The authors investigated whether brain natriuretic peptide (BNP) is related to hypovolemia and hyponatremia after SAH and whether it can differentiate between hyp

  13. Dendrimer D5 is a vector for peptide transport to brain cells.

    Science.gov (United States)

    Sarantseva, S V; Bolshakova, O I; Timoshenko, S I; Kolobov, A A; Schwarzman, A L

    2011-02-01

    Dendrimers are a new class of nonviral vectors for gene or drug transport. Dendrimer capacity to penetrate through the blood-brain barrier remaines little studied. Biotinylated polylysine dendrimer D5, similarly to human growth hormone biotinylated fragment covalently bound to D5 dendrimer, penetrates through the blood-brain barrier and accumulates in Drosophila brain after injection into the abdomen. Hence, D5 dendrimer can serve as a vector for peptide transport to brain cells.

  14. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    Science.gov (United States)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  15. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    Science.gov (United States)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  16. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Gøtze, J P; Fuglsang, Stefan;

    2003-01-01

    subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators......BACKGROUND AND AIMS: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers...... of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis. PATIENTS AND METHODS: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation. RESULTS: Plasma proBNP and BNP were significantly increased...

  17. Identification of nose-to-brain homing peptide through phage display.

    Science.gov (United States)

    Wan, Xiao-Mei; Chen, Yong-Ping; Xu, Wen-Rui; Yang, Wen-Jun; Wen, Long-Ping

    2009-02-01

    Brain delivery of drug molecules through the nasal passage represents a viable approach for bypassing the blood-brain barrier (BBB) but remains a major challenge due to lack of efficient homing carriers. To screen for potential peptides with the ability to transport into the brain via the nasal passage, we applied a C7C phage peptide display library (Ph.D.-C7C) intra-nasally to anesthetized rats and recovered phage from the brain tissue 45 min after phage administration. After three rounds of panning, 10 positive phage clones were selected and sequenced. Clone7, which exhibited highest translocation efficiency, was chosen for further studies. After nasal administration, Clone7 entered the brain within 30 min and exhibited translocation efficiency about 50-fold higher than a random phage. A 11-amino acid synthetic peptide derived from the displayed sequence of Clone7 (ACTTPHAWLCG) efficiently inhibited the nasal-brain translocation of Clone7. Both phage recovery results and fluorescent microscopy images revealed the presence of many more Clone7 phage in the brain than in the liver, kidney and other internal organs after the nasal administration, suggesting that Clone7 bypassed the BBB and entered brain directly. Furthermore, both Clone7 and the ACTTPHAWLCG peptide were found to be heavily distributed along the olfactory nerve after the nasal administration, further suggesting a direct passage route into the brain via the olfactory region. These results demonstrated the feasibility of using the in vivo phage display approach for selecting peptides with the nose-to-brain homing capability and may have implications for the development of novel targeting carriers useful for brain delivery.

  18. Association between plasma brain natriuretic peptide/N-terminal pro-brain natriuretic peptide levels and atrial fibrillation:evidence from a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Liu Yaowu; Xiao Yunyun; Chen Xinguang; Zhang Fengxiang

    2014-01-01

    Background Several small sample-size observational studies evaluated the association of plasma brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) with atrial fibrillation (AF),but the results were contradictory.We aimed to perform a meta-analysis of relevant studies to evaluate the availability of this association.Methods We performed an extensive literature search on PubMed,Web of Science (WOS) and the Cochrane Library databases.Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to assess the strength of association using random effects models.We performed sensitivity and subgroup analyses to explore the potential sources of heterogeneity.We also estimated publication biases.Statistical analyses were performed using the STATA 12.0 software.Results A total of 11 studies including 777 cases and 870 controls were finally analyzed.Overall,the brain natriuretic peptide/N-terminal pro-brain natriuretic peptide levels were higher in atrial fibrillation patients than controls without atrial fibrillation.Results showed that the SMD in the natriuretic peptide levels between cases and controls was 2.68 units (95%CI 1.76 to 3.60); test for overall effect z-score=5.7 (P <0.001).There was significant heterogeneity between individual studies (I2=97.8%; P <0.001).Further analysis revealed that differences in the assay of natriuretic peptide possibly account for this heterogeneity.Conclusions Increased BNP/NT-proBNP levels were associated with the presence of atrial fibrillation.This finding indicates that BNP/NT-proBNP may prove to be a biomarker of an underlying predisposition to AF.

  19. Clinical significance of N-terminal pro-brain natriuretic peptide

    Institute of Scientific and Technical Information of China (English)

    张向阳; 朱继红

    2004-01-01

    @@ Traditionally, it was believed that the natriuretic peptide family (NPs) was composed of four natural peptides, i.e., atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and urodilatin. All of them have the same 17-amino acid ring connected by bisulfate bond, which is essential for their biological activity.1 There are C-terminal and N-terminal tails on the ring. Each peptide encoded by an independent gene has its own tissue specificity and regulation mechanism. It is now suggested that beside the four traditional peptides, their precursors and the peptide fragments released by the activation or hydrolysis of the precursors, such as precursor of ANP and N-terminal proANP (NTANP), precursor of BNP and N-terminal proBNP (NTBNP) are also NPs. Furthermore, an artificially synthesized NP, vasonatrin peptide, is also a new member of NP family. In fish like eel, another peptide named ventricular natriuretic peptide was found. We now have a review on the clinical significance of NTBNP.

  20. CCHamide-2 is an orexigenic brain-gut peptide in Drosophila

    DEFF Research Database (Denmark)

    Ren, Guilin Robin; Hauser, Frank; Rewitz, Kim Furbo;

    2015-01-01

    The neuroendocrine peptides CCHamide-1 and -2, encoded by the genes ccha1 and -2, are produced by endocrine cells in the midgut and by neurons in the brain of Drosophila melanogaster. Here, we used the CRISPR/Cas9 technique to disrupt the ccha1 and -2 genes and identify mutant phenotypes with a f......The neuroendocrine peptides CCHamide-1 and -2, encoded by the genes ccha1 and -2, are produced by endocrine cells in the midgut and by neurons in the brain of Drosophila melanogaster. Here, we used the CRISPR/Cas9 technique to disrupt the ccha1 and -2 genes and identify mutant phenotypes...

  1. Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tingting Lin

    2016-07-01

    Full Text Available Brain delivery of macromolecular therapeutics (e.g., proteins remains an unsolved problem because of the formidable blood–brain barrier (BBB. Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs, new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available pathways (e.g., epithelial tight junctions, uptake by olfactory neurons, transport into brain tissues, and intra-brain diffusion, a low molecular weight protamine (LMWP cell-penetrating peptide was utilized to facilitate nose-to-brain transport. Cell-penetrating peptides (CPP have been widely used to mediate macromolecular delivery through many kinds of biobarriers. Our results show that conjugates of LMWP–proteins are able to effectively penetrate into the brain after intranasal administration. The CPP-based intranasal method highlights a promising solution for protein therapy of brain diseases.

  2. Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides.

    Science.gov (United States)

    Lin, Tingting; Liu, Ergang; He, Huining; Shin, Meong Cheol; Moon, Cheol; Yang, Victor C; Huang, Yongzhuo

    2016-07-01

    Brain delivery of macromolecular therapeutics (e.g., proteins) remains an unsolved problem because of the formidable blood-brain barrier (BBB). Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs, new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available pathways (e.g., epithelial tight junctions, uptake by olfactory neurons, transport into brain tissues, and intra-brain diffusion), a low molecular weight protamine (LMWP) cell-penetrating peptide was utilized to facilitate nose-to-brain transport. Cell-penetrating peptides (CPP) have been widely used to mediate macromolecular delivery through many kinds of biobarriers. Our results show that conjugates of LMWP-proteins are able to effectively penetrate into the brain after intranasal administration. The CPP-based intranasal method highlights a promising solution for protein therapy of brain diseases.

  3. Cre Fused with RVG Peptide Mediates Targeted Genome Editing in Mouse Brain Cells In Vivo

    Directory of Open Access Journals (Sweden)

    Zhiyuan Zou

    2016-12-01

    Full Text Available Cell penetrating peptides (CPPs are short peptides that can pass through cell membranes. CPPs can facilitate the cellular entry of proteins, macromolecules, nanoparticles and drugs. RVG peptide (RVG hereinafter is a 29-amino-acid CPP derived from a rabies virus glycoprotein that can cross the blood-brain barrier (BBB and enter brain cells. However, whether RVG can be used for genome editing in the brain has not been reported. In this work, we combined RVG with Cre recombinase for bacterial expression. The purified RVG-Cre protein cut plasmids in vitro and traversed cell membranes in cultured Neuro2a cells. By tail vein-injecting RVG-Cre into Cre reporter mouse lines mTmG and Rosa26lacZ, we demonstrated that RVG-Cre could target brain cells and achieve targeted somatic genome editing in adult mice. This direct delivery of the gene-editing enzyme protein into mouse brains with RVG is much safer than plasmid- or viral-based methods, holding promise for further applications in the treatment of various brain diseases.

  4. A D-peptide ligand of nicotine acetylcholine receptors for brain-targeted drug delivery.

    Science.gov (United States)

    Wei, Xiaoli; Zhan, Changyou; Shen, Qing; Fu, Wei; Xie, Cao; Gao, Jie; Peng, Chunmei; Zheng, Ping; Lu, Weiyue

    2015-03-01

    Lysosomes of brain capillary endothelial cells are implicated in nicotine acetylcholine receptor (nAChR)-mediated transcytosis and act as an enzymatic barrier for the transport of peptide ligands to the brain. A D-peptide ligand of nAChRs (termed (D)CDX), which binds to nAChRs with an IC50 value of 84.5 nM, was developed by retro-inverso isomerization. (D)CDX displayed exceptional stability in lysosomal homogenate and serum, and demonstrated significantly higher transcytosis efficiency in an in vitro blood-brain barrier monolayer compared with the parent L-peptide. When modified on liposomal surface, (D)CDX facilitated significant brain-targeted delivery of liposomes. As a result, brain-targeted delivery of (D)CDX modified liposomes enhanced therapeutic efficiency of encapsulated doxorubicin for glioblastoma. This study illustrates the importance of ligand stability in nAChRs-mediated transcytosis, and paves the way for developing stable brain-targeted entities.

  5. Peptide Transport through the Blood-Brain Barrier

    Science.gov (United States)

    1989-01-01

    analogues for treatment of membiry,.ACIH analogues for treatmen of post-traumatic epilepsy), should these peptides be capable of traversing the BBB...thus far. In addition, since cationization does not destroy immunoglobulin G antigenicity, the use of cationized immunoglobulins may be used for... aerosolized insulin. Mixed-meal studies and long-term use in Type I diabetes. N. Engl. J. Med. 312:1078-1084. 12. Pardridge, W.M. (1988): Recent advances in

  6. Association between psychological measures and brain natriuretic peptide in heart failure patients

    DEFF Research Database (Denmark)

    Brouwers, Corline; Spindler, Helle; Larsen, Mogens Lytken;

    2012-01-01

    ABSTRACT Objective: Brain natriuretic peptide (BNP) is a promising marker for heart failure diagnosis and prognosis. Although psychological factors also influence heart failure (HF) prognosis, this might be attributed to confounding by BNP. Our aim was to examine the association between multiple...

  7. CCHamide-2 is an orexigenic brain-gut peptide in Drosophila

    DEFF Research Database (Denmark)

    Ren, Guilin Robin; Hauser, Frank; Rewitz, Kim Furbo;

    2015-01-01

    The neuroendocrine peptides CCHamide-1 and -2, encoded by the genes ccha1 and -2, are produced by endocrine cells in the midgut and by neurons in the brain of Drosophila melanogaster. Here, we used the CRISPR/Cas9 technique to disrupt the ccha1 and -2 genes and identify mutant phenotypes with a f...

  8. Dose-response testing of peptides by hippocampal brain slice recording.

    Science.gov (United States)

    Phillips, M I; Palovcik, R A

    1989-01-01

    The brain slice chamber described offers a method of studying, with intracellular electrodes, the relationship of response to dose of peptides. By raising the level of the slices 1 mm above the level of flowing perfusion medium, we can test substances in known concentrations, free from artifacts, during long duration, stable intracellular recordings. Manipulation of Ca2+/Mg2+ ratios in the medium can help to define synaptic and second messenger mediation of the responses. The addition of substances to the perfusion medium in this system could be combined with iontophoresis and/or micropressure techniques. Pathways in the slices may also be stimulated electrically and analyzed for the involvement of various synaptic transmitters. The results with the method so far show distinct differences among the peptides studied. Thus, there are several advantages to this method in establishing the physiological role of peptides in the brain.

  9. Cell-Penetrating Peptides Selectively Cross the Blood-Brain Barrier In Vivo.

    Directory of Open Access Journals (Sweden)

    Sofie Stalmans

    Full Text Available Cell-penetrating peptides (CPPs are a group of peptides, which have the ability to cross cell membrane bilayers. CPPs themselves can exert biological activity and can be formed endogenously. Fragmentary studies demonstrate their ability to enhance transport of different cargoes across the blood-brain barrier (BBB. However, comparative, quantitative data on the BBB permeability of different CPPs are currently lacking. Therefore, the in vivo BBB transport characteristics of five chemically diverse CPPs, i.e. pVEC, SynB3, Tat 47-57, transportan 10 (TP10 and TP10-2, were determined. The results of the multiple time regression (MTR analysis revealed that CPPs show divergent BBB influx properties: Tat 47-57, SynB3, and especially pVEC showed very high unidirectional influx rates of 4.73 μl/(g × min, 5.63 μl/(g × min and 6.02 μl/(g × min, respectively, while the transportan analogs showed a negligible to low brain influx. Using capillary depletion, it was found that 80% of the influxed peptides effectively reached the brain parenchyma. Except for pVEC, all peptides showed a significant efflux out of the brain. Co-injection of pVEC with radioiodinated bovine serum albumin (BSA did not enhance the brain influx of radiodionated BSA, indicating that pVEC does not itself significantly alter the BBB properties. A saturable mechanism could not be demonstrated by co-injecting an excess dose of non-radiolabeled CPP. No significant regional differences in brain influx were observed, with the exception for pVEC, for which the regional variations were only marginal. The observed BBB influx transport properties cannot be correlated with their cell-penetrating ability, and therefore, good CPP properties do not imply efficient brain influx.

  10. C-peptide of preproinsulin-like peptide 7: localization in the rat brain and activity in vitro.

    Science.gov (United States)

    Brailoiu, E; Dun, S L; Gao, X; Brailoiu, G C; Li, J-G; Luo, J J; Yang, J; Chang, J K; Liu-Chen, L-Y; Dun, N J

    2009-03-17

    With the use of a rabbit polyclonal antiserum against a conserved region (54-118) of C-peptide of human preproinsulin-like peptide 7, referred to herein as C-INSL7, neurons expressing C-INSL7-immunoreactivity (irC-INSL7) were detected in the pontine nucleus incertus, the lateral or ventrolateral periaqueductal gray, dorsal raphe nuclei and dorsal substantia nigra. Immunoreactive fibers were present in numerous forebrain areas, with a high density in the septum, hypothalamus and thalamus. Pre-absorption of C-INSL7 antiserum with the peptide C-INSL7 (1 microg/ml), but not the insulin-like peptide 7 (INSL7; 1 microg/ml), also known as relaxin 3, abolished the immunoreactivity. Optical imaging with a voltage-sensitive dye bis-[1,3-dibutylbarbituric acid] trimethineoxonol (DiSBAC4(3)) showed that C-INSL7 (100 nM) depolarized or hyperpolarized a small population of cultured rat hypothalamic neurons studied. Ratiometric imaging studies with calcium-sensitive dye fura-2 showed that C-INSL7 (10-1000 nM) produced a dose-dependent increase in cytosolic calcium concentrations [Ca2+]i in cultured hypothalamic neurons with two distinct patterns: (1) a sustained elevation lasting for minutes; and (2) a fast, transitory rise followed by oscillations. In a Ca2+-free Hanks' solution, C-INSL7 again elicited two types of calcium transients: (1) a fast, transitory increase not followed by a plateau phase, and (2) a transitory rise followed by oscillations. INSL7 (100 nM) elicited a depolarization or hyperpolarization in a small population of hypothalamic neurons, and an increase of [Ca2+]i with two patterns that were dissimilar from that of C-INSL7. [125I]C-INSL7 bindings to rat brain membranes were inhibited by C-INSL7 in a dose-dependent manner; the Kd and Bmax. values were 17.7 +/- 8.2 nM and 45.4 +/- 20.5 fmol/mg protein. INSL7 did not inhibit [125I]C-INSL7 binding to rat brain membranes, indicating that C-INSL7 and INSL7 bind to distinct binding sites. Collectively, our result

  11. 3D printing of layered brain-like structures using peptide modified gellan gum substrates.

    Science.gov (United States)

    Lozano, Rodrigo; Stevens, Leo; Thompson, Brianna C; Gilmore, Kerry J; Gorkin, Robert; Stewart, Elise M; in het Panhuis, Marc; Romero-Ortega, Mario; Wallace, Gordon G

    2015-10-01

    The brain is an enormously complex organ structured into various regions of layered tissue. Researchers have attempted to study the brain by modeling the architecture using two dimensional (2D) in vitro cell culturing methods. While those platforms attempt to mimic the in vivo environment, they do not truly resemble the three dimensional (3D) microstructure of neuronal tissues. Development of an accurate in vitro model of the brain remains a significant obstacle to our understanding of the functioning of the brain at the tissue or organ level. To address these obstacles, we demonstrate a new method to bioprint 3D brain-like structures consisting of discrete layers of primary neural cells encapsulated in hydrogels. Brain-like structures were constructed using a bio-ink consisting of a novel peptide-modified biopolymer, gellan gum-RGD (RGD-GG), combined with primary cortical neurons. The ink was optimized for a modified reactive printing process and developed for use in traditional cell culturing facilities without the need for extensive bioprinting equipment. Furthermore the peptide modification of the gellan gum hydrogel was found to have a profound positive effect on primary cell proliferation and network formation. The neural cell viability combined with the support of neural network formation demonstrated the cell supportive nature of the matrix. The facile ability to form discrete cell-containing layers validates the application of this novel printing technique to form complex, layered and viable 3D cell structures. These brain-like structures offer the opportunity to reproduce more accurate 3D in vitro microstructures with applications ranging from cell behavior studies to improving our understanding of brain injuries and neurodegenerative diseases.

  12. Independent effects of both right and left ventricular function on plasma brain natriuretic peptide

    DEFF Research Database (Denmark)

    Vogelsang, Thomas Wiis; Jensen, Ruben J; Monrad, Astrid L;

    2007-01-01

    BACKGROUND: Brain natriuretic peptide (BNP) is increased in heart failure; however, the relative contribution of the right and left ventricles is largely unknown. AIM: To investigate if right ventricular function has an independent influence on plasma BNP concentration. METHODS: Right (RVEF), left......, which is a strong prognostic marker in heart failure, independently depends on both left and right ventricular systolic function. This might, at least in part, explain why BNP holds stronger prognostic value than LVEF alone....

  13. Delivery and Tracking of Quantum Dot Peptide Bioconjugates in an Intact Developing Avian Brain

    Science.gov (United States)

    Agarwal, Rishabh; Domowicz, Miriam S.; Schwartz, Nancy B.; Henry, Judy; Medintz, Igor; Delehanty, James B.; Stewart, Michael H.; Susumu, Kimihiro; Huston, Alan L.; Deschamps, Jeffrey R.; Dawson, Philip E.; Palomo, Valle; Dawson, Glyn

    2016-01-01

    Luminescent semiconductor ~9.5 nm nanoparticles (quantum dots: QDs) have intrinsic physiochemical and optical properties which enable us to begin to understand the mechanisms of nanoparticle mediated chemical/drug delivery. Here, we demonstrate the ability of CdSe/ZnS core/shell QDs surface functionalized with a zwitterionic compact ligand to deliver a cell-penetrating lipopeptide to the developing chick embryo brain without any apparent toxicity. Functionalized QDs were conjugated to the palmitoylated peptide WGDap-(Palmitoyl)VKIKKP9GGH6, previously shown to uniquely facilitate endosomal escape, and microinjected into the embryonic chick spinal cord canal at embryo day 4 (E4). We were subsequently able to follow the labeling of spinal cord extension into the ventricles, migratory neuroblasts, maturing brain cells, and complex structures such as the choroid plexus. QD intensity extended throughout the brain, and peaked between E8 and E11 when fluorescence was concentrated in the choroid plexus before declining to hatching (E21/P0). We observed no abnormalities in embryonic patterning or embryo survival, and mRNA in situ hybridization confirmed that, at key developmental stages, the expression pattern of genes associated with different brain cell types (brain lipid binding protein, Sox-2, proteolipid protein and Class III-β-Tubulin) all showed a normal labeling pattern and intensity. Our findings suggest that we can use chemically modified QDs to identify and track neural stem cells as they migrate, that the choroid plexus clears these injected QDs/nanoparticles from the brain after E15, and that they can deliver drugs and peptides to the developing brain. PMID:25688887

  14. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    Directory of Open Access Journals (Sweden)

    Caghan Kizil

    Full Text Available Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI, RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  15. The effect of beta-turn structure on the permeation of peptides across monolayers of bovine brain microvessel endothelial cells

    DEFF Research Database (Denmark)

    Sorensen, M; Steenberg, B; Knipp, G T;

    1997-01-01

    PURPOSE: To investigate the effects of the beta-turn structure of a peptide on its permeation via the paracellular and transcellular routes across cultured bovine brain microvessel endothelial cell (BBMEC) monolayers, an in vitro model of the blood-brain barrier (BBB). METHODS: The effective...

  16. Modulation of intercellular junctions by cyclic-ADT peptides as a method to reversibly increase blood-brain barrier permeability.

    Science.gov (United States)

    Laksitorini, Marlyn D; Kiptoo, Paul K; On, Ngoc H; Thliveris, James A; Miller, Donald W; Siahaan, Teruna J

    2015-03-01

    It is challenging to deliver molecules to the brain for diagnosis and treatment of brain diseases. This is primarily because of the presence of the blood-brain barrier (BBB), which restricts the entry of many molecules into the brain. In this study, cyclic-ADT peptides (ADTC1, ADTC5, and ADTC6) have been shown to modify the BBB to enhance the delivery of marker molecules [e.g., (14) C-mannitol, gadolinium-diethylenetriaminepentacetate (Gd-DTPA)] to the brain via the paracellular pathways of the BBB. The hypothesis is that these peptides modulate cadherin interactions in the adherens junctions of the vascular endothelial cells forming the BBB to increase paracellular drug permeation. In vitro studies indicated that ADTC5 had the best profile to inhibit adherens junction resealing in Madin-Darby canine kidney cell monolayers in a concentration-dependent manner (IC50 = 0.3 mM) with a maximal response at 0.4 mM. Under the current experimental conditions, ADTC5 improved the delivery of (14) C-mannitol to the brain about twofold compared with the negative control in the in situ rat brain perfusion model. Furthermore, ADTC5 peptide increased in vivo delivery of Gd-DTPA to the brain of Balb/c mice when administered intravenously. In conclusion, ADTC5 has the potential to improve delivery of diagnostic and therapeutic agents to the brain.

  17. Science Letters: Brain natriuretic peptide: A potential indicator of cardiomyogenesis after autologous mesenchymal stem cell transplantation?

    Institute of Scientific and Technical Information of China (English)

    LI Nan; WANG Jian-an

    2006-01-01

    We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.

  18. Alzheimer's disease and amyloid beta-peptide deposition in the brain: a matter of 'aging'?

    DEFF Research Database (Denmark)

    Moro, Maria Luisa; Collins, Matthew J; Cappellini, Enrico

    2010-01-01

    Biomolecules can experience aging processes that limit their long-term functionality in organisms. Typical markers of protein aging are spontaneous chemical modifications, such as AAR (amino acid racemization) and AAI (amino acid isomerization), mainly involving aspartate and asparagine residues....... Since these modifications may affect folding and turnover, they reduce protein functionality over time and may be linked to pathological conditions. The present mini-review describes evidence of AAR and AAI involvement in the misfolding and brain accumulation of Abeta (amyloid beta-peptide), a central...

  19. The response of circulating brain natriuretic peptide to academic stress in college students.

    Science.gov (United States)

    Amir, Offer; Sagiv, Moran; Eynon, Nir; Yamin, Chen; Rogowski, Ori; Gerzy, Yishay; Amir, Ruthie E

    2010-01-01

    Brain natriuretic peptide (BNP), a cardiac peptide, has been implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. The influence of academic stress on circulating concentration of the N-terminal fragment of BNP precursor (NT-proBNP), and in relation to the stress hormone (cortisol) response was studied in 170 college students undergoing major examinations. Just prior to the examination, we measured self-estimated stress level, systolic, and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma levels of cortisol, and NT-proBNP. These parameters were compared to the participants' baseline measurements, taken at the same hour of a different 'control day', without a major examination to induce stress. Hemodynamic variables (SBP, DBP, and HR) increased on the examination day compared with baseline values ( p stress was marked by a significant decrease in plasma NT-proBNP concentration (-40%, p stress and the NT-proBNP reduction ( p = 0.02). In response to academic stress, the plasma cortisol elevation was accompanied by a marked reduction in plasma NT-proBNP level. These data may indicate that mental stress entails an interface between the HPA axis and the peripheral natriuretic peptide system, leading to reciprocating changes in circulating levels of the corresponding hormones.

  20. Endomorphins, endogenous opioid peptides, provide antioxidant defense in the brain against free radical-induced damage.

    Science.gov (United States)

    Lin, Xin; Yang, Ding-Jian; Cai, Wen-Qing; Zhao, Qian-Yu; Gao, Yan-Feng; Chen, Qiang; Wang, Rui

    2003-11-20

    Oxidative stress has been considered to be a major cause of cellular injuries in a variety of chronic health problems, such as carcinogenesis and neurodegenerative disorders. The brain appears to be more susceptible to oxidative damage than other organs. Therefore, the existence of antioxidants may be essential in brain protective systems. The antioxidative and free radical scavenging effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, have been investigated in vitro. The oxidative damage was initiated by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrocholoride) (AAPH) and hydrogen peroxide (H2O2). The linoleic acid peroxidation, DNA and protein damage were monitored by formation of hydroperoxides, by plasmid pBR 322 DNA nicking assay and single-cell alkaline electrophoresis, and by SDS-polyacrylamide gel electrophoresis. Endomorphins can inhibit lipid peroxidation, DNA strand breakage, and protein fragmentation induced by free radical. Endomorphins also reacted with galvinoxyl radicals in homogeneous solution, and the pseudo-first-order rate constants were determined spectrophotometrically by following the disappearance of galvinoxyl radicals. In all assay systems, EM1 was more potent than EM2 and GSH, a major intracellular water-soluble antioxidant. We propose that endomorphins are one of the protective systems against free radical-induced damage in the brain.

  1. Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.

    Science.gov (United States)

    Ito, Shingo; Ohtsuki, Sumio; Murata, Sho; Katsukura, Yuki; Suzuki, Hiroya; Funaki, Miho; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-01-01

    Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.

  2. Visualization and Quantitative Assessment of the Brain Distribution of Insulin through Nose-to-Brain Delivery Based on the Cell-Penetrating Peptide Noncovalent Strategy.

    Science.gov (United States)

    Kamei, Noriyasu; Shingaki, Tomotaka; Kanayama, Yousuke; Tanaka, Misa; Zochi, Riyo; Hasegawa, Koki; Watanabe, Yasuyoshi; Takeda-Morishita, Mariko

    2016-03-07

    Our recent work suggested that intranasal coadministration with the cell-penetrating peptide (CPP) penetratin increased the brain distribution of the peptide drug insulin. The present study aimed to distinctly certify the ability of penetratin to facilitate the nose-to-brain delivery of insulin by quantitatively evaluating the distribution characteristics in brain using radioactive (64)Cu-NODAGA-insulin. Autoradiography and analysis using a gamma counter of brain areas demonstrated that the accumulation of radioactivity was greatest in the olfactory bulb, the anterior part of the brain closest to the administration site, at 15 min after intranasal administration of (64)Cu-NODAGA-insulin with l- or d-penetratin. The brain accumulation of (64)Cu-NODAGA-insulin with penetratin was confirmed by ELISA using unlabeled insulin in which intact insulin was delivered to the brain after intranasal coadministration with l- or d-penetratin. By contrast, quantification of cerebrospinal fluid (CSF) samples showed increased insulin concentration in only the anterior portion of the CSF at 15 min after intranasal coadministration with l-penetratin. This study gives the first concrete proof that penetratin can accelerate the direct transport of insulin from the nasal cavity to the brain parenchyma. Further optimization of intranasal administration with CPP may increase the efficacy of delivery of biopharmaceuticals to the brain while reducing the risk of systemic drug exposure.

  3. Blood-brain barrier to peptides: (/sup 3/H)gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Ermisch, A.; Ruehle, H.J. (Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften); Klauschenz, E.; Kretzschmar, R. (Akademie der Wissenschaften der DDR, Berlin. Inst. fuer Wirkstofforschung)

    1984-01-01

    After intracarotid injection of (/sup 3/H)gonadotropin-releasing hormone ((/sup 3/H)GnRH) the mean accumulation of radioactivity per unit wet weight of 18 brain samples investigated and the anterior pituitary was 0.38 +- 0.11% g/sup -1/ of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of (/sup 3/H)GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated (/sup 3/H)OH. In BBB-free regions the accumulation of radioactivity was more than 25-fold higher than in BBB-protected regions. The accumulation of (/sup 3/H)GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for (/sup 3/H)GnRH are similar to those for other peptides so far investigated.

  4. Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent

    Directory of Open Access Journals (Sweden)

    Brian Casserly

    2009-11-01

    Full Text Available Brian Casserly, James R KlingerDivision of Pulmonary and Critical Care Medicine, The Memorial Hospital of Rhode Island, Pawtucket, RI, Rhode Island Hospital, Providence, RI, Alpert Medical School of Brown University, Providence, RI, USAAbstract: B-type natriuretic peptide (BNP is a member of the natriuretic peptide family, a group of widely distributed, but evolutionarily conserved, polypeptide mediators that exert myriad cardiovascular effects. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean pulmonary arterial pressure (mPAP and pulmonary vascular resistance (PVR in patients with pulmonary arterial hypertension (PAH. Elevated plasma BNP levels are associated with increased mortality in patients with PAH and a fall in BNP levels after therapy is associated with improved survival. These findings have important clinical implications in that a noninvasive blood test may be used to identify PAH patients at high-risk of decompensation and to guide pulmonary vasodilator therapy. BNP also has several biologic effects that could be beneficial to patients with PAH. However, lack of a convenient method for achieving sustained increases in circulating BNP levels has impeded the development of BNP as a therapy for treating pulmonary hypertension. New technologies that allow transdermal or oral administration of the natriuretic peptides have the potential to greatly accelerate research into therapeutic use of BNP for cor pulmonale and pulmonary vascular diseases. This review will examine the basic science and clinical research that has led to our understanding of the role of BNP in cardiovascular physiology, its use as a biomarker of right ventricular function and its therapeutic potential for managing patients with pulmonary vascular disease.Keywords: brain natriuretic peptide, pulmonary artery hypertension

  5. Biological characteristics of brain natriuretic peptide and its association with central nervous system diseases

    Institute of Scientific and Technical Information of China (English)

    Yubao Huang; Changxiang Yan; Chunjiang Yu

    2007-01-01

    OBJECTIVE: To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide (BNP), and analyze its role in central nervous system diseases.DATA SOURCES: An online search of Pubmed was undertaken to identify articles related to BNP published in English from January 1990 to February 2007 by using the Key words of "brain natriuretic peptide (BNP), central nervous system, subarachnoid hemorrhage (SAH), brain edema, epilepsy". Other articles were searched in China Hospital Knowledge Database (CHKD) by concrete name of journals and title of articles.STUDY SELECTION: The collected articles were primarily screened, those about BNP and its association with central nervous system diseases were selected, whereas the obviously irrelative ones excluded, and the full-texts of the other literatures were searched manually.DATA EXTRACTION: Totally 96 articles were collected, 40 of them were enrolled, and the other 56 were excluded due to repetitive studies or reviews.DATA SYNTHESIS: At present, there are penetrating studies on BNP in the preclinical medicine and clinical medicine of cerebrovascular and cardiovascular diseases, and the investigative outcomes have been gradually applied in clinical practice, and satisfactory results have been obtained. However, the application of BNP in diagnosing and treating central nervous system diseases is still at the experimental phase without -outstanding outcomes, thus the preclinical and clinical studies should be enhanced.CONCLUSION: As a kind of central medium or modulator, BNP plays a certain role in the occurrence,development and termination of central nervous system diseases, the BNP level in serum has certain changing law in AH,brainedema,epilepsy,etc., but the specific mechanisms are unclear.

  6. Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage

    Directory of Open Access Journals (Sweden)

    Eridan eRocha-Ferreira

    2015-02-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5 per 1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy and cognitive disabilities. Even though the brain is considered an immune-privileged site, it has innate and adaptive immune response and can produce complement (C components and antimicrobial peptides (AMPs. Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain.Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS, including neonatal hypoxia-ischemia (HI, resident microglia and astroglia are the main cells providing immune defence to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI-injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins which can chemoattract and promote maturation of dendritic cells, and can also limit inflammation by controlling the viability of these same dendritic cells. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI-injury and the effect of that balance on the

  7. Protective effects of endomorphins, endogenous opioid peptides in the brain, on human low density lipoprotein oxidation.

    Science.gov (United States)

    Lin, Xin; Xue, Li-Ying; Wang, Rui; Zhao, Qian-Yu; Chen, Qiang

    2006-03-01

    Neurodegenerative disorders are associated with oxidative stress. Low density lipoprotein (LDL) exists in the brain and is especially sensitive to oxidative damage. Oxidative modification of LDL has been implicated in the pathogenesis of neurodegenerative diseases. Therefore, protecting LDL from oxidation may be essential in the brain. The antioxidative effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, on LDL oxidation has been investigated in vitro. The peroxidation was initiated by either copper ions or a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). Oxidation of the LDL lipid moiety was monitored by measuring conjugated dienes, thiobarbituric acid reactive substances, and the relative electrophoretic mobility. Low density lipoprotein oxidative modifications were assessed by evaluating apoB carbonylation and fragmentation. Endomorphins markedly and in a concentration-dependent manner inhibited Cu2+ and AAPH induced the oxidation of LDL, due to the free radical scavenging effects of endomorphins. In all assay systems, EM1 was more potent than EM2 and l-glutathione, a major intracellular water-soluble antioxidant. We propose that endomorphins provide protection against free radical-induced neurodegenerative disorders.

  8. Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience.

    Science.gov (United States)

    Yang, Bangkun; Yang, Chun; Ren, Qian; Zhang, Ji-Chun; Chen, Qian-Xue; Shirayama, Yukihiko; Hashimoto, Kenji

    2016-12-01

    Using learned helplessness (LH) model of depression, we measured protein expression of brain-derived neurotrophic factor (BDNF) pro-peptide, BDNF precursors (proBDNF and preproBDNF) in the brain regions of LH (susceptible) and non-LH rats (resilience). Expression of preproBDNF, proBDNF and BDNF pro-peptide in the medial prefrontal cortex of LH rats, but not non-LH rats, was significantly higher than control rats, although expression of these proteins in the nucleus accumbens of LH rats was significantly lower than control rats. This study suggests that regional differences in conversion of BDNF precursors into BDNF and BDNF pro-peptide by proteolytic cleavage may contribute to stress resilience.

  9. Circulating N-terminal brain natriuretic peptide and cardiac function in response to acute systemic hypoxia in healthy humans

    NARCIS (Netherlands)

    I. Heinonen (Ilkka); M. Luotolahti (Matti); O. Vuolteenaho (Olli); M. Nikinmaa (Mikko); A. Saraste (Antti); J. Hartiala (Jaakko); J. Koskenvuo (Juha); J. Knuuti (Juhani); O. Arjamaa (Olli)

    2014-01-01

    textabstractBackground: As it remains unclear whether hypoxia of cardiomyocytes could trigger the release of brain natriuretic peptide (BNP) in humans, we investigated whether breathing normobaric hypoxic gas mixture increases the circulating NT-proBNP in healthy male subjects.Methods: Ten healthy y

  10. Correlation of hyponatremia with plasma renin activity, antidiuretic hormone and brain natri- uretic peptide in chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    富路

    2006-01-01

    Objective To observe the changes of plasma renin activity, antidiuretic hormone and brain natriuretic peptide in chronic heart failure (CHF) and their correlation with hyponatremia. Methods Plasma levels of PRA, ADH, and BNP were measured by radioimmunology in 76 CHF patients. Forty-one out of 76 CHF patients with hyponatremia and 35 CHF patients without hyponatremia

  11. Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection.

    Science.gov (United States)

    Bergman, Peter; Johansson, Linda; Wan, Hong; Jones, Allison; Gallo, Richard L; Gudmundsson, Gudmundur H; Hökfelt, Tomas; Jonsson, Ann-Beth; Agerberth, Birgitta

    2006-12-01

    Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP.

  12. CCHamide-2 Is an Orexigenic Brain-Gut Peptide in Drosophila.

    Directory of Open Access Journals (Sweden)

    Guilin R Ren

    Full Text Available The neuroendocrine peptides CCHamide-1 and -2, encoded by the genes ccha1 and -2, are produced by endocrine cells in the midgut and by neurons in the brain of Drosophila melanogaster. Here, we used the CRISPR/Cas9 technique to disrupt the ccha1 and -2 genes and identify mutant phenotypes with a focus on ccha-2 mutants. We found that both larval and adult ccha2 mutants showed a significantly reduced food intake as measured in adult flies by the Capillary Feeding (CAFE assay (up to 72% reduced food intake compared to wild-type. Locomotion tests in adult flies showed that ccha2 mutants had a significantly reduced locomotor activity especially around 8 a.m. and 8 p.m., where adult Drosophila normally feeds (up to 70% reduced locomotor activity compared to wild-type. Reduced larval feeding is normally coupled to a delayed larval development, a process that is mediated by insulin. Accordingly, we found that the ccha2 mutants had a remarkably delayed development, showing pupariation 70 hours after the pupariation time point of the wild-type. In contrast, the ccha-1 mutants were not developmentally delayed. We also found that the ccha2 mutants had up to 80% reduced mRNA concentrations coding for the Drosophila insulin-like-peptides-2 and -3, while these concentrations were unchanged for the ccha1 mutants. From these experiments we conclude that CCHamide-2 is an orexigenic peptide and an important factor for controlling developmental timing in Drosophila.

  13. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain-Adipocyte Axis.

    Science.gov (United States)

    Geloneze, Bruno; de Lima-Júnior, José Carlos; Velloso, Lício A

    2017-02-23

    The complexity of neural circuits that control food intake and energy balance in the hypothalamic nuclei explains some of the constraints involved in the prevention and treatment of obesity. Two major neuronal populations present in the arcuate nucleus control caloric intake and energy expenditure: one population co-expresses orexigenic agouti-related peptide (AgRP) and neuropeptide Y and the other expresses the anorexigenic anorectic neuropeptides proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). In addition to integrating signals from neurotransmitters and hormones, the hypothalamic systems that regulate energy homeostasis are affected by nutrients. Fat-rich diets, for instance, elicit hypothalamic inflammation (reactive activation and proliferation of microglia, a condition named gliosis). This process generates resistance to the anorexigenic hormones leptin and insulin, contributing to the genesis of obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have increasingly been used to treat type 2 diabetes mellitus. One compound (liraglutide) was recently approved for the treatment of obesity. Although most studies suggest that GLP-1RAs promote weight loss mainly due to their inhibitory effect on food intake, other central effects that have been described for native GLP-1 and some GLP-1RAs in rodents and humans encourage future clinical trials to explore additional mechanisms that potentially underlie the beneficial effects observed with this drug class. In this article we review the most relevant data exploring the mechanisms involved in the effects of GLP-1RAs in the brain-adipocyte axis.

  14. CART peptide and opioid addiction: Expression changes in male rat brain.

    Science.gov (United States)

    Bakhtazad, A; Vousooghi, N; Garmabi, B; Zarrindast, M R

    2016-06-14

    Previous studies have shown the prominence of cocaine- and amphetamine-regulated transcript (CART) peptide in rewarding and reinforcing effects of drugs of abuse specially psychostimulants. The data regarding the effects of different stages of opioid addiction on CART expression and the interconnection between CART and opioids are not much available. Here we have studied the changes in the expression level of CART mRNA and protein in various parts of the brain reward pathway in different stages of opioid addiction. Groups of male rats received acute low-dose (10mg/kg), acute high-dose (80mg/kg) and chronic escalating doses of morphine. In addition, withdrawal and abstinence states were evaluated after injection of naloxone (1mg/kg) and long-term maintenance of addicted animals, respectively. Expression of CART mRNA in the brain was measured by real-time PCR method. Western blotting was used to quantify the protein level. CART mRNA and protein were both up-regulated in high-dose morphine-administered animals and also in the withdrawal group in the nucleus accumbens (NAc), striatum and prefrontal cortex (PFC). In the addicted group, CART mRNA and protein were both down-regulated in NAc and striatum. In the abstinent group, CART mRNA was down-regulated in NAc. In the hippocampus, the only observed change was the up-regulation of CART mRNA in the withdrawal group. We suggest that the modulatory role of CART peptide in rewarding and reinforcing effects of opioids weakens when opioids are used for a long time and is stimulated when acute stress such as naloxone-induced withdrawal syndrome or acute high-dose administration of morphine occurs to the animal.

  15. Influence of Peptide Transporter 2 (PEPT2) on the Distribution of Cefadroxil in Mouse Brain: A Microdialysis Study.

    Science.gov (United States)

    Chen, Xiaomei; Keep, Richard F; Liang, Yan; Zhu, Hao-Jie; Hammarlund-Udenaes, Margareta; Hu, Yongjun; Smith, David E

    2017-02-10

    Peptide transporter 2 (PEPT2) is a high-affinity low-capacity transporter belonging to the proton-coupled oligopeptide transporter family. Although many aspects of PEPT2 structure-function are known, including its localization in choroid plexus and neurons, its regional activity in brain, especially extracellular fluid (ECF), is uncertain. In this study, the pharmacokinetics and regional brain distribution of cefadroxil, a ß-lactam antibiotic and PEPT2 substrate, were investigated in wildtype and Pept2 null mice using in vivo intracerebral microdialysis. Cefadroxil was infused intravenously over 4 hours at 0.15 mg/min/kg, and samples obtained from plasma, brain ECF, cerebrospinal fluid (CSF) and brain tissue. A permeability-surface area experiment was also performed in which 0.15 mg/min/kg cefadroxil was infused intravenously for 10 min, and samples obtained from plasma and brain tissues. Our results showed that PEPT2 ablation significantly increased the brain ECF and CSF levels of cefadroxil (2- to 2.5-fold). In contrast, there were no significant differences between wildtype and Pept2 null mice in the amount of cefadroxil in brain cells. The unbound volume of distribution of cefadroxil in brain was 60% lower in Pept2 null mice indicating an uptake function for PEPT2 in brain cells. Finally, PEPT2 did not affect the influx clearance of cefadroxil, thereby, ruling out differences between the two genotypes in drug entry across the blood-brain barriers. These findings demonstrate, for the first time, the impact of PEPT2 on brain ECF as well as the known role of PEPT2 in removing peptide-like drugs, such as cefadroxil, from the CSF to blood.

  16. Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B W

    2016-01-01

    BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we record...... cortex. Sumatriptan injection reversed these changes. CONCLUSION: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.......BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...

  17. Comparison of Linear and Cyclic His-Ala-Val Peptides in Modulating the Blood-Brain Barrier Permeability: Impact on Delivery of Molecules to the Brain.

    Science.gov (United States)

    Alaofi, Ahmed; On, Ngoc; Kiptoo, Paul; Williams, Todd D; Miller, Donald W; Siahaan, Teruna J

    2016-02-01

    The aim of this study is to evaluate the effect of peptide cyclization on the blood-brain barrier (BBB) modulatory activity and plasma stability of His-Ala-Val peptides, which are derived from the extracellular 1 domain of human E-cadherin. The activities to modulate the intercellular junctions by linear HAV4 (Ac-SHAVAS-NH2), cyclic cHAVc1 (Cyclo(1,8)Ac-CSHAVASC-NH2), and cyclic cHAVc3 (Cyclo(1,6)Ac-CSHAVC-NH2) were compared in in vitro and in vivo BBB models. Linear HAV4 and cyclic cHAVc1 have the same junction modulatory activities as assessed by in vitro MDCK monolayer model and in situ rat brain perfusion model. In contrast, cyclic cHAVc3 was more effective than linear HAV4 in modulating MDCK cell monolayers and in improving in vivo brain delivery of Gd-DTPA on i.v. administration in Balb/c mice. Cyclic cHAVc3 (t1/2 = 12.95 h) has better plasma stability compared with linear HAV4 (t1/2 = 2.4 h). The duration of the BBB modulation was longer using cHAVc3 (2-4 h) compared with HAV4 (<1 h). Both HAV4 and cHAVc3 peptides also enhanced the in vivo brain delivery of IRdye800cw-PEG (25 kDa) as detected by near IR imaging. The result showed that cyclic cHAVc3 peptide had better activity and plasma stability than linear HAV4 peptide.

  18. Reversible Opening of Intercellular Junctions of Intestinal Epithelial and Brain Endothelial Cells With Tight Junction Modulator Peptides.

    Science.gov (United States)

    Bocsik, Alexandra; Walter, Fruzsina R; Gyebrovszki, Andrea; Fülöp, Lívia; Blasig, Ingolf; Dabrowski, Sebastian; Ötvös, Ferenc; Tóth, András; Rákhely, Gábor; Veszelka, Szilvia; Vastag, Monika; Szabó-Révész, Piroska; Deli, Mária A

    2016-02-01

    The intercellular junctions restrict the free passage of hydrophilic compounds through the paracellular clefts. Reversible opening of the tight junctions of biological barriers is investigated as one of the ways to increase drug delivery to the systemic circulation or the central nervous system. Six peptides, ADT-6, HAV-6, C-CPE, 7-mer (FDFWITP, PN-78), AT-1002, and PN-159, acting on different integral membrane and linker junctional proteins were tested on Caco-2 intestinal epithelial cell line and a coculture model of the blood-brain barrier. All peptides tested in nontoxic concentrations showed a reversible tight junctions modulating effect and were effective to open the paracellular pathway for the marker molecules fluorescein and albumin. The change in the structure of cell-cell junctions was verified by immunostaining for occludin, claudin-4,-5, ZO-1, β-catenin, and E-cadherin. Expression levels of occludin and claudins were measured in both models. We could demonstrate a selectivity of C-CPE, ADT-6, and HAV-6 peptides for epithelial cells and 7-mer and AT-1002 peptides for brain endothelial cells. PN-159 was the most effective modulator of junctional permeability in both models possibly acting via claudin-1 and -5. Our results indicate that these peptides can be effectively and selectively used as potential pharmaceutical excipients to improve drug delivery across biological barriers.

  19. A novel peptide delivers plasmids across blood-brain barrier into neuronal cells as a single-component transfer vector.

    Directory of Open Access Journals (Sweden)

    Ailing Fu

    Full Text Available There is no data up to now to show that peptide can deliver plasmid into brain as a single-component transfer vector. Here we show that a novel peptide, RDP (consisted of 39 amino acids, can be exploited as an efficient plasmid vector for brain-targeting delivery. The plasmids containing Lac Z reporter gene (pVAX-Lac Z and BDNF gene (pVAX-BDNF are complexed with RDP and intravenously injected into mice. The results of gel retardation assay show that RDP enables to bind DNA in a dose-dependent manner, and the X-Gal staining identity that Lac Z is specifically expressed in the brain. Also, the results of Western blot and immunofluorescence staining of BDNF indicate that pVAX-BDNF complexed with RDP can be delivered into brain, and show neuroprotective properties in experimental Parkinson's disease (PD model. The results demonstrate that RDP enables to bind and deliver DNA into the brain, resulting in specific gene expression in the neuronal cells. This strategy provides a novel, simple and effective approach for non-viral gene therapy of brain diseases.

  20. A novel peptide delivers plasmids across blood-brain barrier into neuronal cells as a single-component transfer vector.

    Science.gov (United States)

    Fu, Ailing; Zhang, Miaomiao; Gao, Feiyan; Xu, Xingran; Chen, Zhangbao

    2013-01-01

    There is no data up to now to show that peptide can deliver plasmid into brain as a single-component transfer vector. Here we show that a novel peptide, RDP (consisted of 39 amino acids), can be exploited as an efficient plasmid vector for brain-targeting delivery. The plasmids containing Lac Z reporter gene (pVAX-Lac Z) and BDNF gene (pVAX-BDNF) are complexed with RDP and intravenously injected into mice. The results of gel retardation assay show that RDP enables to bind DNA in a dose-dependent manner, and the X-Gal staining identity that Lac Z is specifically expressed in the brain. Also, the results of Western blot and immunofluorescence staining of BDNF indicate that pVAX-BDNF complexed with RDP can be delivered into brain, and show neuroprotective properties in experimental Parkinson's disease (PD) model. The results demonstrate that RDP enables to bind and deliver DNA into the brain, resulting in specific gene expression in the neuronal cells. This strategy provides a novel, simple and effective approach for non-viral gene therapy of brain diseases.

  1. Effects of lamprey PQRFamide peptides on brain gonadotropin-releasing hormone concentrations and pituitary gonadotropin-β mRNA expression.

    Science.gov (United States)

    Daukss, Dana; Gazda, Kristen; Kosugi, Takayoshi; Osugi, Tomohiro; Tsutsui, Kazuyoshi; Sower, Stacia A

    2012-06-01

    Within the RFamide peptide family, PQRFamide peptides that include neuropeptide FF and AF possess a C-terminal Pro-Gln-Arg-Phe-NH(2) motif. We previously identified PQRFamide peptides, lamprey PQRFa, PQRFa-related peptide (RP)-1 and -RP-2 by immunoaffinity purification in the brain of lamprey, one of the most ancient vertebrate species [13]. Lamprey PQRFamide peptide precursor mRNA was expressed in regions predicted to be involved in neuroendocrine regulation in the hypothalamus. However, the putative function(s) of lamprey PQRFamide peptides (PQRFa, PQRFa-RP-1 and PQRFa-RP-2) were not examined nor was the distribution of PQRFamide peptides examined in other tissues besides the brain. The objective of this study was to determine tissue distribution of lamprey PQRFamide peptide precursor mRNA, and to examine the effects of PQRFamide peptides on brain gonadotropin-releasing hormone (GnRH)-I, -II, and -III protein concentrations, and pituitary gonadotropin (GTH)-β mRNA expression in adult lampreys. Lamprey PQRFamide peptide precursor mRNA was expressed in the eye and the brain. Lamprey PQRFa at 100 μg/kg increased brain concentrations of lamprey GnRH-II compared with controls. PQRFa, PQRFa-RP-1 and PQRFa-RP-2 did not significantly change brain protein concentrations of either lamprey GnRH-I, -III, or lamprey GTH-β mRNA expression in the pituitary. These data suggest that one of the PQRFamide peptides may act as a neuroregulator of at least the lamprey GnRH-II system in adult female lamprey.

  2. A novel bioassay for the activity determination of therapeutic human brain natriuretic peptide (BNP.

    Directory of Open Access Journals (Sweden)

    Lei Yu

    Full Text Available BACKGROUND: Recombinant human brain natriuretic peptide (rhBNP is an important peptide-based therapeutic drug indicated for the treatment of acute heart failure. Accurate determination of the potency of therapeutic rhBNP is crucial for the safety and efficacy of the drug. The current bioassay involves use of rabbit aortic strips, with experiments being complicated and time-consuming and markedly variable in results. Animal-less methods with better precision and accuracy should be explored. We have therefore developed an alternative cell-based assay, which relies on the ability of BNP to induce cGMP production in HEK293 cells expressing BNP receptor guanylyl cyclase-A. METHODOLOGY/PRINCIPAL FINDINGS: An alternative assay based on the measurement of BNP-induced cGMP production was developed. Specifically, the bioassay employs cells engineered to express BNP receptor guanylyl cyclase-A (GCA. Upon rhBNP stimulation, the levels of the second messager cGMP in these cells drastically increased and subsequently secreted into culture supernatants. The quantity of cGMP, which corresponds to the rhBNP activity, was determined using a competitive ELISA developed by us. Compared with the traditional assay, the novel cell-based assay demonstrated better reproducibility and precision. CONCLUSION/SIGNIFICANCE: The optimized cell-based assay is much simpler, more rapid and precise compared with the traditional assay using animal tissues. To our knowledge, this is the first report on a novel and viable alternative assay for rhBNP potency analysis.

  3. Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles.

    Science.gov (United States)

    Kanazawa, T; Akiyama, F; Kakizaki, S; Takashima, Y; Seta, Y

    2013-12-01

    The potential for RNA-based agents to serve as effective therapeutics for central nerve systems (CNS) disorders has been successfully demonstrated in vitro. However, the blood-brain barrier limits the distribution of systemically administered therapeutics to the CNS, posing a major challenge for drug development aimed at combatting CNS disorders. Therefore, the development of effective strategies to enhance siRNA delivery to the brain is of great interest in clinical and pharmaceutical fields. To improve the efficiency of small interfering RNA (siRNA) delivery to the brain, we developed a nose-to-brain delivery system combined with cell-penetrating peptide (CPP) modified nano-micelles comprising polyethylene glycol-polycaprolactone (PEG-PCL) copolymers conjugated with the CPP, Tat (MPEG-PCL-Tat). In this study, we describe intranasal brain delivery of siRNA or dextran (Mw: 10,000 Da) as a model siRNA, by using MPEG-PCL-Tat. Intranasal delivery of dextran with MPEG-PCL-Tat improved brain delivery compared to intravenous delivery of dextran either with or without MPEG-PCL-Tat. We also studied the intranasal transfer of MPEG-PCL-Tat to the brain via the olfactory and trigeminal nerves, the putative pathways to the brain from the nasal cavity. We found that MPEG-PCL-Tat accelerated transport along the olfactory and trigeminal nerve pathway because of its high permeation across the nasal mucosa.

  4. Some Brain Peptides Regulating the Secretion of Digestive Enzymes in the Indian Meal Moth, Plodia Interpunctella (Lepidoptera: Pyralidae

    Directory of Open Access Journals (Sweden)

    Sajjadian Seyede Minoo

    2014-07-01

    Full Text Available The Indian meal moth, Plodia interpunctella (Hübner (Lepidoptera: Pyralidae is a destructive polyphagous pest of many stored products. To interfere with the physiological processes, especially digestion, of the larval pest, more information on the regulatory mechanisms is needed. The brain extract from 1-day-old last instar larvae of P. interpunctella was examined. In the bioassays, the midguts were treated with the brain extract, and the carbohydrase and protease activities were measured. The brain extract showed increasing dose-dependent effects on α-amylase, α-glucosidase, β-glucosidase, α-galactosidase, β-galactosidase, and trypsin secretion in the larval midgut. The extract was further characterised and partially purified using high performance liquid chromatography (HPLC. Several peptides were determined in the brain extract regulating hydrolase activities in the larval midgut of the pest.

  5. Detection of left ventricular enlargement and impaired systolic function with plasma N-terminal pro brain natriuretic peptide concentrations

    DEFF Research Database (Denmark)

    Grønning, Bjørn Aaris; Nilsson, Jens C.; Søndergaard, Lars

    2002-01-01

    BACKGROUND: Brain- and N-terminal pro brain natriuretic peptide (NT-proBNP) have been identified as promising markers for heart failure. However, previous studies have revealed that they may hold insufficient diagnostic power for implementation into clinical practice because of a significant...... to investigate the diagnostic potential of NT-proBNP with magnetic resonance imaging as the reference method for the cardiac measurements. METHODS: Forty-eight patients with stable symptomatic heart failure in New York Heart Association functional classifications II to IV were examined once with blood samples...

  6. Brain-targeted co-delivery of therapeutic gene and peptide by multifunctional nanoparticles in Alzheimer's disease mice.

    Science.gov (United States)

    Liu, Yang; An, Sai; Li, Jianfeng; Kuang, Yuyang; He, Xi; Guo, Yubo; Ma, Haojun; Zhang, Yu; Ji, Bin; Jiang, Chen

    2016-02-01

    Multifunctional nanocarriers are increasingly promising for disease treatment aimed to regulate multiple pathological dysfunctions and overcome barriers in drug delivery. Here we develop a multifunctional nanocarrier for Alzheimer's disease (AD) treatment by achieving therapeutic gene and peptide co-delivery to brain based on PEGylated dendrigraft poly-l-lysines (DGLs) via systemic administration. The dendritic amine-rich structure of DGLs provides plenty reaction sites and positive charge for drug loading. Successful co-delivery of drugs overcoming the blood-brain barrier by brain-targeted ligand modification was demonstrated both in vitro and in vivo. The pharmacodynamics study of the system following multiple-dosing treatment was verified in transgenic AD mice. Down-regulation of the key enzyme in amyloid-β formation was achieved by delivering non-coding RNA plasmid. Simultaneous delivery of the therapeutic peptide into brain leads to reduction of neurofibrillary tangles. Meanwhile, memory loss rescue in AD mice was also observed. Taken together, the multifunctional nanocarrier provides an excellent drug co-delivery platform for brain diseases.

  7. Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide

    DEFF Research Database (Denmark)

    Carlsen, Christian Malchau; Bay, Morten; Kirk, Vibeke

    2012-01-01

    The aim of this study was to assess the epidemiological features and prognosis of heart failure with preserved ejection fraction (HFPEF) and to compare these findings with those from patients with reduced ejection fraction. Furthermore the effects of N-terminal pro brain natriuretic peptide (NT......-proBNP) requirement in the heart failure diagnosis were assessed by repeating the analyses in the subgroup of patients with elevated NT-proBNP....

  8. Resting and dobutamine stress test induced serum concentrations of brain natriuretic peptide in German Shepherd dogs.

    Science.gov (United States)

    Spasojević Kosić, Ljubica; Trailović, Dragiša R; Matunović, Radomir

    2012-12-01

    Studies of clinical uses of brain natriuretic peptide (BNP) represent one of the most important advances in cardiology since the introduction of echocardiography as a clinical diagnostic procedure. Defining the clinical potential of BNP in canine cardiology has not been completed yet. The aim of this study is to measure BNP concentrations in healthy German Shepherd dogs of different ages as a baseline in resting and when conventional protocol of the dobutamine stress test (DST) is applied to dogs. Concentrations of BNP were measured in blood serum by the radioimmunoassay method. The values of BNP concentrations were compared to cardiac parameters obtained by standard cardiac diagnostic procedures (radiology, electrocardiography and echocardiography). No significant differences in serum BNP concentrations existed in dogs of different ages. A statistically significant increase in BNP concentrations was registered after DST. These changes in BNP concentrations were related to ST/T electrocardiographic changes, and correlated to changes in the left ventricular internal diameter in systole (LVESD). These data suggest that BNP is not increased in aged dogs with normal cardiac systolic function and renal function, and that myocardial ischemia leads to a significant increase in BNP concentrations even in dogs with normal left ventricular function.

  9. Changes of Plasma Levels of Brain Natriuretic Peptide in Patients with Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    Pei Xiaoyang; Pan Ying; Hu Xuesong; Li Song; Xu Yawei; Yu Xuejing

    2006-01-01

    Objectives To investigate the changes of plasma brain natriuretic peptide (BNP) levels in patients with chronic heart failure (CHF).Methods Plasma BNP concentrations in patients with CHF (n=56) and in normal controls (n=60) were measured with specific radioimmunoassay. Left ventricular ejection fraction in patients with chronic heart failure was measured with 99mTc gated cardiac blood pool scintigraphy. Results The results showed that Plasma BNP concentrations in patients with CHF were significantly higher than normal controls (223±79 ng/L vs 40±15 ng/L, P < 0.01). Plasma BNP concentrations had a significant negative correlation with left ventricular ejection fractions(r=-0.68, P <0.01 ). Conclusions These results indicates that Plasma BNP levels are increased in patients with CHF, and they markedly increased according to the severity of heart failure classified by NYHA classification. The plasma BNP levels may be a biochemical parameter for evaluating the left ventricular function.

  10. Cortical Brain Connectivity and B-Type Natriuretic Peptide in Patients With Congestive Heart Failure.

    Science.gov (United States)

    Vecchio, Fabrizio; Miraglia, Francesca; Valeriani, Lavinia; Scarpellini, Maria Gabriella; Bramanti, Placido; Mecarelli, Oriano; Rossini, Paolo M

    2015-07-01

    The brain has a high level of complexity and needs continuous oxygen supply. So it is clear that any pathological condition, or physiological (aging) change, in the cardiovascular system affects functioning of the central nervous system. We evaluated linear aspects of the relationship between the slowness of cortical rhythms, as revealed by the modulation of a graph connectivity parameter, and congestive heart failure (CHF), as a reflection of neurodegenerative processes. Eyes-closed resting electroencephalographic (EEG) data of 10 patients with CHF were recorded by 19 electrodes positioned according the international 10-20 system. Graph theory function (normalized characteristic path length λ) was applied to the undirected and weighted networks obtained by lagged linear coherence evaluated by eLORETA software, therefore getting rid of volumetric propagation influences. The EEG frequency bands of interest were: delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). The analysis between B-type natriuretic peptide (BNP) values and λ showed positive correlation in delta, associated with a negative correlation in alpha 2 band. Namely, the higher the severity of the disease (as revealed by the BNP vales), the higher the λ in delta, and lower in alpha 2 band. Results suggest that delta and alpha λ indices are good markers of the severity of CHF.

  11. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats.

    NARCIS (Netherlands)

    Armbruszt, S.; Abraham, H.; Figler, M.; Kozicz, T.L.; Hajnal, A.

    2013-01-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the

  12. ProSAAS-derived peptides are differentially processed and sorted in mouse brain and AtT-20 cells.

    Directory of Open Access Journals (Sweden)

    Jonathan H Wardman

    Full Text Available ProSAAS is the precursor for some of the most abundant peptides found in mouse brain and other tissues, including peptides named SAAS, PEN, and LEN. Both SAAS and LEN are found in big and little forms due to differential processing. Initial processing of proSAAS is mediated by furin (and/or furin-like enzymes and carboxypeptidase D, while the smaller forms are generated by secretory granule prohormone convertases and carboxypeptidase E. In mouse hypothalamus, PEN and big LEN colocalize with neuropeptide Y. In the present study, little LEN and SAAS were detected in mouse hypothalamus but not in cell bodies of neuropeptide Y-expressing neurons. PEN and big LEN show substantial colocalization in hypothalamus, but big LEN and little LEN do not. An antiserum to SAAS that detects both big and little forms of this peptide did not show substantial colocalization with PEN or big LEN. To further study this, the AtT-20 cells mouse pituitary corticotrophic cell line was transfected with rat proSAAS and the distribution of peptides examined. As found in mouse hypothalamus, only some of the proSAAS-derived peptides colocalized with each other in AtT-20 cells. The two sites within proSAAS that are known to be efficiently cleaved by furin were altered by site-directed mutagenesis to convert the P4 Arg into Lys; this change converts the sequences from furin consensus sites into prohormone convertase consensus sites. Upon expression of the mutated form of proSAAS in AtT-20 cells, there was significantly more colocalization of proSAAS-derived peptides PEN and SAAS. Taken together, these results indicate that proSAAS is initially cleaved in the Golgi or trans-Golgi network by furin and/or furin-like enzymes and the resulting fragments are sorted into distinct vesicles and further processed by additional enzymes into the mature peptides.

  13. Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells.

    Science.gov (United States)

    Park, See-Hyoung; Yoon, Young Ii; Moon, Hyoungwon; Lee, Ga-Hyun; Lee, Byung-Heon; Yoon, Tae-Jong; Lee, Hak Jong

    2016-07-01

    Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells. In addition, WST-1 assay results showed that MB-Lipo (Dox)‑IL4RTP inhibited the proliferation of U87MG cells IL4R‑dependently. This was confirmed by western blotting of γH2AX, phospho (Ser15)-p53, p53 and p21 which are signal transduction proteins involved in DNA damage response and cell cycle arrest. Taken together, these results indicate that MB-Lipo (Dox)-IL4RTP represents a promising ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

  14. Effects of Wen Dan Tang on insomnia-related anxiety and levels of the brain-gut peptide Ghrelin

    Institute of Scientific and Technical Information of China (English)

    Liye Wang; Binghe Guan; Xiaolan Liu; Yuehan Song; Feng Li; Yan Liu; Jie Ma; Meng Mao; Fengzhi Wu; Ying Wu; Sinai Li

    2014-01-01

    Ghrelin, a brain-gut peptide that induces anxiety and other abnormal emotions, contributes to the effects of insomnia on emotional behavior. In contrast, the traditional Chinese Medi-cine remedy Wen Dan Tang reduces insomnia-related anxiety, which may perhaps correspond to changes in the brain-gut axis. This suggests a possible relationship between Wen Dan Tang’s pharmacological mechanism and the brain-gut axis. Based on this hypothesis, a sleep-deprived rat model was induced and Wen Dan Tang was administered using oral gavage during model es-tablishment. Wen Dan Tang signiifcantly reduced insomnia-related anxiety and prevented Ghrelin level decreases following sleep deprivation, especially in the hypothalamus. Increased expression of Ghrelin receptor mRNA in the hypothalamus was also observed, suggesting that reduced anxi-ety may be a result of Wen Dan Tang’s regulation of Ghrelin-Ghrelin receptors.

  15. Kadar N-Terminal Pro-Brain Natriuretic Peptide sebagai Prediktor Luaran Klinis Sindrom Koroner Akut

    Directory of Open Access Journals (Sweden)

    Florencia Idajanti Tandhana

    2012-06-01

    Full Text Available Plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP levels may reflect the severity of ischemia, although there is no necrosis. A transient ischemia which can increase the heart wall stretch would induces BNP synthesis and release. Synthesis and release of BNP are comparable with the severity of ischemia. The aim of this study was to analyze whether NT-proBNP levels in patients with acute coronary syndrome (ACS can be used as a predictor for clinical outcome. Studies was held since January to March 2010. Subject were patients with ACS who came to emergency room Dr. Hasan Sadikin Hospital Bandung and were clinically diagnosed according to World Health Organization criteria. Subjects which were suited with the inclusion criteria, stored until assayed. NT-pro BNP concentration was examined by electrochemiluminescence immunoassay method along with creatine kinase muscle brain (enzymatic method and cardiac troponin T (quantitative method. Statistical analysis was performed using the one-sample Kolmogorov-Smirnov test for verifying normality, normally distributed data were analyzed using parametric analysis and abnormal distributed data was assayed using multiple logistic regression analysis to determine the parameters which can be used as predictor for clinical outcome in patients with ACS. Multiple logistic regression analysis on 83 subjects showed predictive value of NT-proBNP levels with OR=1.00, which mean there was no different likelihood in patients with high and low concentration of NT-proBNP to have longer hospitality duration. NT-proBNP β coefficient of 0.001 states that every addition of 1,000 pg/mL of NT-proBNP concentration will increase the length of hospitality duration for one day. On convalesce subjects, the most significant predictive value for predicting clinical outcome cTnT was more better than NT-proBNP concentration in patients with ACS (OR=32.53, 95%CI; 0.58–1,819.26. In conclusions, NT-proBNP is not a major

  16. The association between brain natriuretic peptide and tissue Doppler parameters in children with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Taliha Öner

    2016-01-01

    Full Text Available In this study, we investigated the association between brain natriuretic peptide (BNP levels and tissue Doppler imaging measurements and also screening for deadly mutations in patients with hypertrophic cardiomyopathy (HCM. We enrolled 20 patients diagnosed with HCM (age:10.7±5 years (1-17, 85% male, weight:42.25±23.10 kg, height:141.80±32.45 cm and 20 age, gender and body weight-matched control subjects. We performed electrocardiography, transthoracic echocardiography, and tissue Doppler echocardiography in each group, as well as genetic tests (for Arg403Gln, Arg453Cys, Arg719Trp and Arg719Gln mutations in MYH7 Exons 13, 14, 19 and BNP in the patients. The patients were divided into two groups according to the presence (Group 1 or absence (Group 2 of left ventricular (LV outflow tract obstruction. QTc dispersion and the LV ejection fraction and left atrial (LA volume index were increased in Group 1. The LA volume index and the mitral and septal E/Ea ratio and septum Z-score were increased while the mitral lateral annulus and septal annulus Ea wave velocities and the mitral and tricuspid E/A ratio were decreased in patients with high levels of BNP compared to those with normal BNP levels. There were no mutations that are associated with increased risk of sudden death found in patients included in this study. In the light of our data, we conclude that such parameters BNP levels above the 98 pg/mL, septal thickness Z-score ˃6, and higher mitral and septal E/Ea ratios can be used for management of patients with HCM according to life-threatening conditions.

  17. Alteration of Plasma Brain Natriuretic Peptide Level After Acute Moderate Exercise in Professional Athletes

    Directory of Open Access Journals (Sweden)

    Homa Sheikhani

    2011-12-01

    Full Text Available Background: Cardiac fatigue or myocardial damage following exercise until complete exhaustion can increase blood levels of brain natriuretic peptide (BNP in athletes. Objectives: The aim of the present study was to investigate the effect of resistance and acute moderate aerobic exercise on alterations in BNP levels in professional athletes. Materials and Methods: Forty professional athletes who had at least 3 years of a championship background in track and field (aerobic group or body building (resistance group volunteered to participate in the present study. Track and field athletes (n = 20 were requested to run 8 km at 60% to 70% of maximum heart rate. Body building athletes (n = 20 performed a resistance training session of 5 exercises in 3 sets of 10 repetitions at 75% of 1 RM (bench press, seated row, leg extension, leg curl, and leg press. Before and immediately after the exercise, plasma BNP levels of both groups of athletes were measured by PATHFASTTM NT-proBNP assay, an immunochemiluminescent assay using two polyclonal antibodies in sandwich test format, on a PATHFASTTM automated analyzer. Results: Plasma BNP levels immediately following exercise increased significantly as compared with baseline values. Plasma BNP concentrations in the aerobic group were significantly higher than in the resistance group before and after exercise. Moreover, the increase in mean BNP concentrations in aerobic athletes was 7 times more than in resistance athletes. Conclusions: BNP levels in athlete who performed distance exercises increased significantly compared with resistance training. Possibly exercise program type, intensity of exercise, volume of exercise program, and field sport can be factors of changes in BNP levels

  18. Brain reward-system activation in response to anticipation and consumption of palatable food is altered by glucagon-like peptide-1 receptor activation in humans

    NARCIS (Netherlands)

    van Bloemendaal, L.; Veltman, D. J.; ten Kulve, J. S.; Groot, P. F. C.; Ruhe, H. G.; Barkhof, F.; Sloan, J. H.; Diamant, M.; Ijzerman, R. G.

    2015-01-01

    AimTo test the hypothesis that food intake reduction after glucagon-like peptide-1 (GLP-1) receptor activation is mediated through brain areas regulating anticipatory and consummatory food reward. MethodsAs part of a larger study, we determined the effects of GLP-1 receptor activation on brain respo

  19. Identification and distribution of gonadotropin-releasing hormone-like peptides in the brain of horseshoe crab Tachypleus tridentatus

    Institute of Scientific and Technical Information of China (English)

    HUANG Huiyang; LI Linming; YE Haihui; FENG Biyun; LI Shaojing

    2013-01-01

    Gonadotropin-releasing hormone (GnRH) is a crucial peptide for the regulation of reproduction.Using immunological techniques,we investigated the presence of GnRH in horseshoe crab Tachypleus tridentatus.Octopus GnRH-like immunoreactivity,tunicate GnRH-like immunoreactivity,and lamprey GnRH-I-like immunoreactivity were detected in the neurons and fibers of the protocerebrum.However,no mammal GnRH-like immunoreactivity or lamprey GnRH-Ⅲ-like immunoreactivity was observed.Our results suggest that a GnRH-like factor,an ancient peptide,existed in the brain of T.tridentatus and may be involved in the reproductive endocrine system.

  20. Brain-natriuretic peptide and cyclic guanosine monophosphate as biomarkers of myxomatous mitral valve disease in dogs

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Falk, Bo Torkel; Teerlink, Tom;

    2011-01-01

    Elevations in the plasma concentrations of natriuretic peptides correlate with increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study correlates the severity of MMVD with the plasma concentrations of the biomarkers N-terminal fragment of the pro-brain-natriuretic peptide...... (NT-proBNP) and its second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the l-arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of nitric oxide availability. The study included 75 dogs sub-divided into five groups based on severity of MMVD as assessed...... by clinical examination and echocardiography. Plasma NT-proBNP and cGMP concentrations increased with increasing valve dysfunction and were significantly elevated in dogs with heart failure. The cGMP:NT-proBNP ratio decreased significantly in dogs with heart failure, suggesting the development of natriuretic...

  1. Evidence that a synthetic amyloid-ß oligomer-binding peptide (ABP) targets amyloid-ß deposits in transgenic mouse brain and human Alzheimer's disease brain.

    Science.gov (United States)

    Chakravarthy, Balu; Ito, Shingo; Atkinson, Trevor; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Whitfield, James

    2014-03-14

    The synthetic ~5 kDa ABP (amyloid-ß binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents Aß1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering Aß oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice.

  2. Plasma pro-brain natriuretic peptide and electrocardiographic changes in combination improve risk prediction in persons without known heart disease

    DEFF Research Database (Denmark)

    Jørgensen, Peter G; Jensen, Jan S; Appleyard, Merete

    2015-01-01

    BACKGROUND: Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine...... cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death. RESULTS: ECG changes were present in 907...

  3. Heart murmur and N-terminal pro-brain natriuretic peptide as predictors of death in 2977 consecutive hospitalized patients

    DEFF Research Database (Denmark)

    Iversen, Kasper; Nielsen, O.W.; Kirk, V.

    2008-01-01

    Background: Little is known about the prognostic importance of murmur in unselected patients. It is difficult to distinguish between innocent and significant murmurs. N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and BNP have recently been shown to be useful in small series of patients......-pro-BNP, discovery of valvular heart disease by echocardiography yielded no additional prognostic information. Conclusions: Detection of a cardiac murmur during routine medical examination of hospitalized patients is associated with increased risk of death within a year. A blood test for NT-pro-BNP gives significant...

  4. Prognostic usefulness of anemia and N-terminal pro-brain natriuretic peptide in outpatients with systolic heart failure

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Kistorp, Caroline N

    2007-01-01

    N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and anemia are predictors of outcome in systolic heart failure. It is currently unclear how these 2 markers interact in particular with regard to the prognostic information carried by each risk marker. We therefore tested the hypothesis...... that anemia (World Health Organization criteria, hemoglobin levels ... prospectively at the baseline visit to our heart failure clinic (inclusion criterion left ventricular ejection fraction anemia was 27%. In a multivariate logistic regression model, anemia (p = 0...

  5. Association between brain natriuretic peptide, markers of inflammation and the objective and subjective response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Brouwers, Corline; Versteeg, Henneke; Meine, Mathias;

    2014-01-01

    Introduction: Studies suggest that cardiac resynchronization therapy (CRT) can induce a decrease in brain natriuretic peptide (BNP) and systemic inflammation, which may be associated with CRT-response. However, the evidence is inconclusive. We examined levels of BNP and inflammatory markers from...... ventricular end systolic volume; subjective CRT-response was defined as an improvement of ⩾10 points in patient-reported health status assessed with the Kansas City Cardiomyopathy Questionnaire. Plasma BNP and markers of inflammation (CRP, IL-6, TNFα, sTNFr1 and sTNFr2) were measured at three time points......=27.31, pinflammation. This indicates that response to CRT...

  6. Brain natriuretic peptide is a potent vasodilator in aged human microcirculation and shows a blunted response in heart failure patients

    DEFF Research Database (Denmark)

    Edvinsson, Marie-Louise; Uddman, Erik; Edvinsson, Lars;

    2014-01-01

    BACKGROUND: Brain natriuretic peptide (BNP) is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects (CHF). BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic...... in the forearm was measured by laser Doppler Flowmetry. Local heating (+44°C, 10 min) was used to evoke a maximum local dilator response. RESULTS: Non-invasive iontophoretic administration of either BNP or acetylcholine (ACh), a known endothelium-dependent dilator, elicited an increase in local flow. The nitric...

  7. Prognostic Importance of Exercise Brain Natriuretic Peptide in Asymptomatic Chronic Organic Severe Mitral Regurgitation: An Observational Study

    Science.gov (United States)

    Sinha, Santosh Kumar; Garg, Shalini; Thakur, Ramesh; Krishna, Vinay; Singh, Karandeep; Sachan, Mohit; Goel, Amit; Razi, Mahamdula; Pandey, Umeshwar; Varma, Chandra Mohan

    2016-01-01

    Background The optimal timing of surgery in patients with chronic organic severe mitral regurgitation (MR) continues to be debated, especially for those who are asymptomatic. The aim of the study was to determine independent and additive prognostic value of exercise brain natriuretic peptide (eBNP) in patients with severe asymptomatic MR and normal left ventricular ejection fraction (LVEF). Methods Two hundred twenty-three consecutive patients with severe MR defined by effective regurgitant orifice (ERO) area ≥ 40 mm2 and/or residual volume ≥ 60 mL, LVEF > 60%, and normal LV end-systolic diameter free survival and might be considered for early MVR.

  8. Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis.

    Science.gov (United States)

    De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G

    2015-03-01

    Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes.

  9. Brain natriuretic peptide as a predictor of heart failure in patients with permanent pacemaker

    Directory of Open Access Journals (Sweden)

    Jelić Vera

    2007-01-01

    Full Text Available Introduction: Brain natriuretic peptide (BNP has a role in control of cardiovascular and renal functions. Objective The objective was to assess the predictive value of BNP levels for development of heart failure in patients with permanent pacemakers. Method In patients with implanted DDD pacemakers, BNP levels were measured at rest and after exercise testing, on DDD and VVI modes. There were 42 patients (25 males; 59.5%, without symptoms or signs of coronary disease or heart failure, and with normal echocardiograms. According to BNP levels, the patients were divided into three groups: with BNP levels lower than 80 pg/ml, BNP ranging from 81-150 pg/ml, and BNP levels over 151 pg/ml. Results In the first group (27 patients, BNP levels were significantly higher on VVI compared to DDD mode, both at rest and after exercise (p<0.01, with all BNP levels within normal range. In the second group (5 pts, BNP levels at rest were also significantly higher on VVI than on DDD mode, p<0.05. After exercise, these values were also higher on VVI compared to DDD mode, but without statistical significance. The third group (10 pts as a whole had higher BNP values on VVI compared to DDD mode, with no statistical significance. In patients from this group who later developed heart failure, BNP levels were found to be significantly lower on DDD as opposed to VVI mode at rest, p<0.05, and even higher significance was found after exercise, p<0.01. After 6-year follow-up, 2 out of 5 patients from the second group developed dilated cardiomyopathy, and 8/10 patients in the third group experienced heart failure with LV EF 34.1±10%, LV EDD 6.1±0.42 cm, LV ESD 4.8±0.45 cm. Five of these patients died within the follow-up period. Conclusion The increased BNP levels can be valuable for early screening of patients with higher risk of heart failure. In patients with increased BNP at the time of pacemaker implantation, DDD pacing is a modality of choice.

  10. Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides

    OpenAIRE

    Tingting Lin; Ergang Liu; Huining He; Meong Cheol Shin; Cheol Moon; Yang, Victor C.; Yongzhuo Huang

    2016-01-01

    Brain delivery of macromolecular therapeutics (e.g., proteins) remains an unsolved problem because of the formidable blood–brain barrier (BBB). Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs, new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available path...

  11. Neural effects of gut- and brain-derived glucagon-like peptide-1 and its receptor agonist.

    Science.gov (United States)

    Katsurada, Kenichi; Yada, Toshihiko

    2016-04-01

    Glucagon-like peptide-1 (GLP-1) is derived from both the enteroendocrine L cells and preproglucagon-expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP-1 is cleaved by dipeptidyl peptidase-4 yielding a half-life of less than 2 min, it is plausible that the gut-derived GLP-1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP-1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain-derived GLP-1 is restriction of feeding. GLP-1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP-1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase-4, and is highly likely to act on the brain by passing through the blood-brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP-1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP-1 and the pathway by which peripheral GLP-1 informs the brain, and then discuss recent findings on the central effects of GLP-1 and GLP-1 receptor agonists.

  12. A nanoengineered peptidic delivery system with specificity for human brain capillary endothelial cells

    DEFF Research Database (Denmark)

    Wu, Linping; Moghimi, Seyed Moein

    2016-01-01

    The blood–brain-barrier (BBB) is a formidable obstacle for successful translocation of many drug molecules from the systemic circulation into the brain, and therefore a major challenge for neurotherapeutics. Nanoparticles may offer some opportunities for delivery of bioactive molecules into brain...

  13. The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin

    Directory of Open Access Journals (Sweden)

    M.C. Beinfeld

    2001-11-01

    Full Text Available This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant.

  14. Brain Natriuretic Peptide Stimulates Lipid Metabolism through Its Receptor NPR1 and the Glycerolipid Metabolism Pathway in Chicken Adipocytes.

    Science.gov (United States)

    Huang, H Y; Zhao, G P; Liu, R R; Li, Q H; Zheng, M Q; Li, S F; Liang, Z; Zhao, Z H; Wen, J

    2015-11-03

    Brain natriuretic peptide (BNP) is related to lipid metabolism in mammals, but its effect and the molecular mechanisms underlying it in chickens are incompletely understood. We found that the level of natriuretic peptide precursor B (NPPB, which encodes BNP) mRNA expression in high-abdominal-fat chicken groups was significantly higher than that of low-abdominal-fat groups. Partial correlations indicated that changes in the weight of abdominal fat were positively correlated with NPPB mRNA expression level. In vitro, compared with the control group, preadipocytes with NPPB interference showed reduced levels of proliferation, differentiation, and glycerin in media. Treatments of cells with BNP led to enhanced proliferation and differentiation of cells and glycerin concentration, and mRNA expression of its receptor natriuretic peptide receptor 1 (NPR1) was upregulated significantly. In cells exposed to BNP, 482 differentially expressed genes were identified compared with controls without BNP. Four genes known to be related to lipid metabolism (diacylglycerol kinase; lipase, endothelial; 1-acylglycerol-3-phosphate O-acyltransferase 1; and 1-acylglycerol-3-phosphate O-acyltransferase 2) were enriched in the glycerolipid metabolism pathway and expressed differentially. In conclusion, BNP stimulates the proliferation, differentiation, and lipolysis of preadipocytes through upregulation of the levels of expression of its receptor NPR1 and key genes enriched in the glycerolipid metabolic pathway.

  15. Neuroprotective peptide ADNF-9 in fetal brain of C57BL/6 mice exposed prenatally to alcohol

    Directory of Open Access Journals (Sweden)

    Karty Jonathan A

    2011-10-01

    Full Text Available Abstract Background A derived peptide from activity-dependent neurotrophic factor (ADNF-9 has been shown to be neuroprotective in the fetal alcohol exposure model. We investigated the neuroprotective effects of ADNF-9 against alcohol-induced apoptosis using TUNEL staining. We further characterize in this study the proteomic architecture underlying the role of ADNF-9 against ethanol teratogenesis during early fetal brain development using liquid chromatography in conjunction with tandem mass spectrometry (LC-MS/MS. Methods Pregnant C57BL/6 mice were exposed from embryonic days 7-13 (E7-E13 to a 25% ethanol-derived calorie [25% EDC, Alcohol (ALC] diet, a 25% EDC diet simultaneously administered i.p. ADNF-9 (ALC/ADNF-9, or a pair-fed (PF liquid diet. At E13, fetal brains were collected from 5 dams from each group, weighed, and frozen for LC-MS/MS procedure. Other fetal brains were fixed for TUNEL staining. Results Administration of ADNF-9 prevented alcohol-induced reduction in fetal brain weight and alcohol-induced increases in cell death. Moreover, individual fetal brains were analyzed by LC-MS/MS. Statistical differences in the amounts of proteins between the ALC and ALC/ADNF-9 groups resulted in a distinct data-clustering. Significant upregulation of several important proteins involved in brain development were found in the ALC/ADNF-9 group as compared to the ALC group. Conclusion These findings provide information on potential mechanisms underlying the neuroprotective effects of ADNF-9 in the fetal alcohol exposure model.

  16. 脑钠肽临床应用进展%Advances in Clinical Application of Brain Natriuretic Peptide

    Institute of Scientific and Technical Information of China (English)

    金涛; 戴晓莉; 胡玉霞

    2012-01-01

    Brain natriuretic peptide (BNP) is one of the most attentive cardiovascular physiological biomarkers in recent years, It is a major peptide hormone secreted by the heart, and it plays an important compensatory role in maintaining heart normal structure and function. It's has satisfaction row, urination, vasodilators, and lowering blood pressure and so on in the human body, inhibitting RAAS system and sympathetic nervous system. BNP has a closing relationship with differential diagnosis of dyspnea, myocardial infarction, hypertension, fibrillation, cardiomyopathy, pulmonary embolism and so on. Now this paper will reviewe on BNP's research progress.%脑钠肽(brain natriuretic peptide,BNP)是近年倍受关注的心血管生物标记物,BNP是一种主要由心脏分泌的肽类激素,在心脏维持其正常结构和功能的中起着重要的作用,它具有利钠、利尿、扩血管、降压、拮抗RAAS系统、抑制交感神经兴奋等作用.它已超过原来仅作为心衰的诊断检测指标范畴.研究表明BNP与呼吸困难的鉴别诊断、心肌梗死、高血压、心房颤动、心肌病、肺栓塞等关系密切,现就BNP的临床研究进展作一综述.

  17. Systemic inflammatory response syndrome following burns is mediated by brain natriuretic peptide/natriuretic peptide A receptor-induced shock factor 1 signaling pathway.

    Science.gov (United States)

    Xu, Yang-Cheng; Luo, Cheng-Qun; Li, Xiong

    2016-10-01

    The aim of this study was to determine whether systemic inflammatory response syndrome (SIRS) in burn patients is mediated by the brain natriuretic peptide (BNP)/natriuretic peptide A receptor (NPRA)-induced heat shock factor 1 (HSF-1) signalling pathway. Mononuclear cells (MNCs) that were isolated from patients with burn injuries and SIRS mouse models and a RAW264.7 cell line were treated with normal serum or serum obtained from animals with burn injuries. In parallel, small hairpin RNAs (shRNAs) against BNP or NPRA were transfected in both cell types. Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA) were used to detect protein expression and inflammatory factor levels, respectively. We found that interleukin (IL)-12, tumour necrosis factor (TNF)-α, C-reactive protein (CRP), and BNP levels were increased and IL-10 levels were decreased in the plasma and MNCs in vivo in the animal model of SIRS. Additionally, NPRA was upregulated, whereas HSF-1 was downregulated in monocytes in vivo. Treatment of RAW264.7 cells with burn serum or BNP induced IL-12, TNF-α, and CRP secretion as well as HSF-1 expression. Finally, silencing BNP with shRNA interrupted the effect of burn serum on RAW264.7 cells, and silencing NPRA blocked burn serum- and BNP-mediated changes in RAW264.7 cells. These results suggest that the interaction of NPRA with BNP secreted from circulatory MNCs as well as mononuclear macrophages leads to inflammation via HSF-1 during SIRS development following serious burn injury.

  18. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    OpenAIRE

    Rutten, Joost

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the fi rst natriuretic peptide to be discovered and in humans ANP is predominantly formed in the cardiomyocytes of the atria.2 B-type natriuretic peptide (BNP) was fi rst discovered in porcine brain hen...

  19. Pregnancy Vaccination with Gold Glyco-Nanoparticles Carrying Listeria monocytogenes Peptides Protects against Listeriosis and Brain- and Cutaneous-Associated Morbidities

    Directory of Open Access Journals (Sweden)

    Ricardo Calderón-Gonzalez

    2016-08-01

    Full Text Available Listeriosis is a fatal infection for fetuses and newborns with two clinical main morbidities in the neonatal period, meningitis and diffused cutaneous lesions. In this study, we vaccinated pregnant females with two gold glyconanoparticles (GNP loaded with two peptides, listeriolysin peptide 91–99 (LLO91–99 or glyceraldehyde-3-phosphate dehydrogenase 1–22 peptide (GAPDH1–22. Neonates born to vaccinated mothers were free of bacteria and healthy, while non-vaccinated mice presented clear brain affections and cutaneous diminishment of melanocytes. Therefore, these nanoparticle vaccines are effective measures to offer pregnant mothers at high risk of listeriosis interesting therapies that cross the placenta.

  20. Zinc(II) interactions with brain-derived neurotrophic factor N-terminal peptide fragments: inorganic features and biological perspectives.

    Science.gov (United States)

    Travaglia, Alessio; La Mendola, Diego; Magrì, Antonio; Pietropaolo, Adriana; Nicoletti, Vincenzo G; Grasso, Giuseppe; Malgieri, Gaetano; Fattorusso, Roberto; Isernia, Carla; Rizzarelli, Enrico

    2013-10-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal differentiation, growth, and survival; it is involved in memory formation and higher cognitive functions. The N-terminal domain of BDNF is crucial for the binding selectivity and activation of its specific TrkB receptor. Zn(2+) ion binding may influence BDNF activity. Zn(2+) complexes with the peptide fragment BDNF(1-12) encompassing the sequence 1-12 of the N-terminal domain of BDNF were studied by means of potentiometry, electrospray mass spectrometry, NMR, and density functional theory (DFT) approaches. The predominant Zn(2+) complex species, at physiological pH, is [ZnL] in which the metal ion is bound to an amino, an imidazole, and two water molecules (NH2, N(Im), and 2O(water)) in a tetrahedral environment. DFT-based geometry optimization of the zinc coordination environment showed a hydrogen bond between the carboxylate and a water molecule bound to zinc in [ZnL]. The coordination features of the acetylated form [AcBDNF(1-12)] and of a single mutated peptide [BDNF(1-12)D3N] were also characterized, highlighting the role of the imidazole side chain as the first anchoring site and ruling out the direct involvement of the aspartate residue in the metal binding. Zn(2+) addition to the cell culture medium induces an increase in the proliferative activity of the BDNF(1-12) peptide and of the whole protein on the SHSY5Y neuroblastoma cell line. The effect of Zn(2+) is opposite to that previously observed for Cu(2+) addition, which determines a decrease in the proliferative activity for both peptide and protein, suggesting that these metals might discriminate and modulate differently the activity of BDNF.

  1. The Appetite-Inducing Peptide, Ghrelin, Induces Intracellular Store-Mediated Rises in Calcium in Addiction and Arousal-Related Laterodorsal Tegmental Neurons in Mouse Brain Slices

    DEFF Research Database (Denmark)

    Hauberg, Katrine; Kohlmeier, Kristi Anne

    2015-01-01

    Ghrelin, a gut and brain peptide, has recently been shown to be involved in motivated behavior and regulation of the sleep and wakefulness cycle. The laterodorsal tegmental nucleus (LDT) is involved in appetitive behavior and control of the arousal state of an organism, and accordingly, behavioral...... this peptide has been shown in other cell types to lead to rises in calcium via release of calcium from intracellular stores. To determine whether ghrelin induced intracellular calcium rises in mouse LDT neurons, we conducted calcium imaging studies in LDT brain slices loaded with the calcium binding dye, Fura...

  2. Distribution of Vasotocin- and Vasoactive Intestinal Peptide-like Immunoreactivity in the Brain of Blue Tit (Cyanistes coeruleus

    Directory of Open Access Journals (Sweden)

    Catherine Monique Montagnese

    2015-07-01

    Full Text Available Blue tits (Cyanistes coeruleus are songbirds, used as model animals in numerous studies covering a wide field of research. Nevertheless, the distribution of neuropeptides in the brain of this avian species remains largely unknown. Here we present some of the first results on distribution of Vasotocine (AVT and Vasoactive intestinal peptide (VIP in the brain of males and females of this songbird species, using immunohistochemistry mapping.The bulk of AVT-like cells are found in the hypothalamic supraoptic, paraventricular and suprachiasmatic nuclei, bed nucleus of the stria terminalis, and along the lateral forebrain bundle. Most AVT-like fibers course toward the median eminence, some reaching the arcopallium, and lateral septum. Further terminal fields occur in the dorsal thalamus, ventral tegmental area and pretectal area. Most VIP-like cells are in the lateral septal organ and arcuate nucleus. VIP-like fibers are distributed extensively in the hypothalamus, preoptic area, lateral septum, diagonal band of Broca. They are also found in the bed nucleus of the stria terminalis, amygdaloid nucleus of taenia, robust nucleus of the arcopallium, caudo-ventral hyperpallium, nucleus accumbens and the brainstem. Taken together, these results suggest that both AVT and VIP immunoreactive structures show similar distribution to other avian species, emphasizing evolutionary conservatism in the history of vertebrates. The current study may enable future investigation into the localization of AVT and VIP, in relation to behavioral and ecological traits in the brain of tit species.

  3. The influence of anaemia on stroke prognosis and its relation to N-terminal pro-brain natriuretic peptide

    DEFF Research Database (Denmark)

    Nybo, M; Kristensen, S R; Mickley, H;

    2007-01-01

    Anaemia is a negative prognostic factor for patients with heart failure and impaired renal function, but its role in stroke patients is unknown. Furthermore, anaemia has been shown to influence the level of N-terminal pro-brain natriuretic peptide (NT-proBNP), but this is only investigated...... in patients with heart failure, not in stroke patients. Two-hundred-and-fifty consecutive, well-defined ischemic stroke patients were investigated. Mortality was recorded at 6 months follow-up. Anaemia was diagnosed in 37 patients (15%) in whom stroke severity was worse than in the non-anaemic group, whilst...... the prevalence of renal affection, smoking and heart failure was lower. At 6 months follow-up, 23 patients were dead, and anaemia had an odds ratio of 4.7 when adjusted for age, Scandinavian Stroke Scale and a combined variable of heart and/or renal failure and/or elevation of troponin T using logistic...

  4. Effect of electroacupuncturein Weijing points on gastroin testinal interdigestive migrating motor complex and brain gut peptides release in dogs

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Interdigestive gastrointestinal migratingmotor complex (MMC) activities were recorded by strain gauge implanted on the serosa in 7 conscious dogs. We studied theffects of electroacupuncture (EAP) Weijing points Zusanli (S36), Tianshu (S25), Liangmen (S21) on MMC and release of motilin and gastrin, and compared them with that of EAP Pangguangjing points. The results indicated that EAP Weijing points could not only strengthen MMC contractions in antrum, duodenum and proximal jejunum, but also increase plasma concentration of motilin and gastrin. Anti-motilin serum, proglumide, atropine, or hexamethonium could markedly block the effect of EAP on reinforcing MMC contraction and release of motilin and gastrin. We could get the conclusions that such enhancing effect of EAP Weijing points on MMC and brain-gut peptides release is mediated by motilin and gastrin, on which both cholinergic nerve and sympathetic nerve play important roles.

  5. Natriuretic Peptides, Diagnostic and Prognostic Biomarkers

    NARCIS (Netherlands)

    J.H.W. Rutten (Joost)

    2010-01-01

    textabstractIn humans, the natriuretic peptide family consists of three different types of peptides: atrial natriuretic peptide (synonym: atrial natriuretic factor), B-type natriuretic peptide (synonym: brain natriuretic peptide) and C-natriuretic peptide.1 Atrial natriuretic peptide (ANP) was the f

  6. Amyloid-β peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: A review of experimental and clinical studies

    Directory of Open Access Journals (Sweden)

    Parmenion P. Tsitsopoulos

    2013-06-01

    Full Text Available Traumatic brain injury (TBI survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in most severe TBI patients, results in accumulation of amyloid precursor protein (APP. Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ peptides, a hallmark finding in Alzheimer’s disease (AD. At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF using cerebral microdialysis and/or cerebrospinal fluid (CSF following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques and the complexity of TBI in available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using e.g. rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long

  7. Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage.

    Science.gov (United States)

    Knauf, Claude; Cani, Patrice D; Perrin, Christophe; Iglesias, Miguel A; Maury, Jean François; Bernard, Elodie; Benhamed, Fadilha; Grémeaux, Thierry; Drucker, Daniel J; Kahn, C Ronald; Girard, Jean; Tanti, Jean François; Delzenne, Nathalie M; Postic, Catherine; Burcelin, Rémy

    2005-12-01

    Intestinal glucagon-like peptide-1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9-39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state.

  8. Brain Activation by Peptide Pro-Leu-Gly-NH (MIF-1

    Directory of Open Access Journals (Sweden)

    Reas S. Khan

    2010-01-01

    Full Text Available MIF-1 (Pro-Leu-Gly-NH2 is a tripeptide for which the therapeutic potential in Parkinson's disease and depression has been indicated by many studies. However, the cellular mechanisms of action of MIF-1 are not yet clear. Here, we show the specific brain regions responsive to MIF-1 treatment by c-Fos mapping, and determine the kinetics of cellular signaling by western blotting of pERK, pSTAT3, and c-Fos in cultured neurons. The immunoreactivity of c-Fos was increased 4 hours after MIF-1 treatment in brain regions critically involved in the regulation of mood, anxiety, depression, and memory. The number of cells activated was greater after peripheral treatment (intravenous delivery than after intracerebroventricular injection. In cultured SH-SY5Y neuronal cells, c-Fos was induced time- and dose-dependently. The activation of cellular c-Fos was preceded by a transient increase of mitogen-activated protein kinase pERK but a reduction of phosphorylated Signal Transducer and Activator of Transcription (pSTAT3 initially. We conclude that MIF-1 can modulate multiple cellular signals including pERK, and pSTAT3 to activate c-Fos. The cellular activation in specific brain regions illustrates the biochemical and neuroanatomical basis underlying the therapeutic effect of MIF-1 in Parkinson's disease and depression.

  9. TDP6, a brain-derived neurotrophic factor-based trkB peptide mimetic, promotes oligodendrocyte myelination.

    Science.gov (United States)

    Wong, Agnes W; Giuffrida, Lauren; Wood, Rhiannon; Peckham, Haley; Gonsalvez, David; Murray, Simon S; Hughes, Richard A; Xiao, Junhua

    2014-11-01

    Brain-derived neurotrophic factor (BDNF) plays critical roles in the development and maintenance of the central (CNS) and peripheral nervous systems (PNS). BDNF exerts its biological effects via tropomyosin-related kinase B (TrkB) and the p75 neurotrophin receptor (p75NTR). We have recently identified that BDNF promotes CNS myelination via oligodendroglial TrkB receptors. In order to selectively target TrkB to promote CNS myelination, we have used a putative TrkB agonist, a small multicyclic peptide (tricyclic dimeric peptide 6, TDP6) previously described by us that structurally mimics a region of BDNF that binds TrkB. We confirmed that TDP6 acts as a TrkB agonist as it provoked autophosphorylation of TrkB and its downstream signalling effector extracellular related-kinase 1 and 2 (Erk1/2) in primary oligodendrocytes. Using an in vitro myelination assay, we show that TDP6 significantly promotes myelination by oligodendrocytes in vitro, as evidenced by enhanced myelin protein expression and an increased number of myelinated axonal segments. In contrast, a second, structurally distinct BDNF mimetic (cyclo-dPAKKR) that targets p75NTR had no effect upon oligodendrocyte myelination in vitro, despite the fact that cyclo-dPAKKR is a very effective promoter of peripheral (Schwann cell) myelination. The selectivity of TDP6 was further verified by using TrkB-deficient oligodendrocytes, in which TDP6 failed to promote myelination, indicating that the pro-myelinating effect of TDP6 is oligodendroglial TrkB-dependent. Together, our results demonstrate that TDP6 is a novel BDNF mimetic that promotes oligodendrocyte myelination in vitro via targeting TrkB.

  10. 脑利钠肽BNP的临床应用进展%Clinical Research Progress of Brain Natriuretic Peptide

    Institute of Scientific and Technical Information of China (English)

    杨欣; 任斌辉; 许林

    2013-01-01

    脑利钠肽(BNP)是利钠肽系统中的重要成员之一.BNP是一种包含了32个氨基酸的多肽,于1998年被日本学者从猪脑中发现并提取出来.它主要由心室肌细胞受压分泌,故可以反映左心室壁承受的压力大小.BNP可产生排钠利尿效应,参与调节水、电解质平衡,减少血浆容量;同时还可扩张血管,从而降低体循环血管阻力.有大量研究显示,血浆BNP水平在充血性心力衰竭中增高,因此它可作为心衰的有效监测指标之一,并且在临床上得到了广泛应用.此外,BNP还可作为早期心血管疾病的筛查高危因素.近年来BNP在诊疗心血管疾病、呼吸困难、肺栓塞、慢性阻塞性肺疾病和肺癌过程中均显示出重要作用.现就BNP在上述多学科领域中运用的新进展作一综述.%BNP (Brain natriuretic peptide) is an important member of natriuretic peptide system. It is a 32-amino acid polypep-tide. It was firstly discovered and extracted in porcine brain in Japan. It is mainly from secretion in the cardiac ventricles in response to dilatation or an increase of pressure, so it can reflect the pressure of the left ventricular wall. Its biological function is a tension-decreasing effect based on natriuresis, diuresis and vasodilatation effects. A lot of experimental evidences revealed that the plasma concentration of BNP was raised in congestive heart failure, so it is an effective marker for monitoring heart failure, widely used in clinical practice. Further, BNP could be used to identify patients who are at higher risk for developing cardiovascular events. This article reviews the current state of the BNP in diagnosing and treating cardiovascular disease, dyspnea, pulmonary embolism, chronic obstructive pulmonary disease and lung cancer.

  11. Research on polychaete annelid osmoregulatory peptide(s) by immunocytochemical and physiological approaches. Computer reconstruction of the brain and evidence for a role of angiotensin-like molecules in Nereis (Hediste) diversicolor OF Müller.

    Science.gov (United States)

    Fewou, J; Dhainaut-Courtois, N

    1995-01-01

    Immunohistochemical and physiological studies were carried out on Nereis (Hediste) diversicolor OF Müller in order to obtain evidence concerning the neuroendocrine control of polychaete osmoregulation. The occurrence in this animal of peptides immunologically related to mammalian angiotensin II and I (AII and AI) and oxytocin (OT) was demonstrated in the brain and the ventral nerve cord (VNC) perikarya and nerve fibres as well as in a few peripheral structures (peripheral nerves, epithelial cells, nuchal organ, intestine and nephridia). The exact localization of immunoreactive cells was achieved by serial sections of brain and ventral nerve cord followed by a three-dimensional reconstruction of brain ganglionic nuclei using the CATIA ('Conception Assistée Tridimensionnelle Inter Active') Dassault system program. Injections of polyclonal antisera against AII or OT provoked a partial inhibition of the increase in body weight in Nereis exposed to hypo-osmotic medium. The effect of a-AII seemed more pronounced than that of a-OT. In a subsequent test, injections of synthetic AII and AII-amide (peptide recently isolated from an achaete (Salzet et al (1995) J Biol Chem 270, 1575-1582) enhanced the increase in body weight and, therefore, strengthened the hypothesis of the neuroendocrine control of Nereis osmoregulation. The antidiuretic effect of both synthetic peptides in this study was indicative of the exact role of Nereis endogenous molecule(s). AII was less potent than its amidated form. If AI-like can easily be struck off the list of putative endogenous osmoregulatory factors, the role of OT-like substance in Nereis osmoregulation, which is partially demonstrated in this study, needs to be clarified by further physiological experiments using injection of synthetic peptide(s) or endogenous substance(s). All these results are discussed and compared to those recently obtained in an achaete annelid (Salzet et al (1993) Brain Res 631, 247-255; Salzet et al (1993) Brain

  12. The synthetic NCAM-derived peptide, FGL, modulates the transcriptional response to traumatic brain injury

    DEFF Research Database (Denmark)

    Pedersen, Martin Volmer; Helweg-Larsen, Rehannah Borup; Nielsen, Finn Cilius;

    2008-01-01

    Cerebral responses to traumatic brain injury (TBI) include up- and downregulation of a vast number of proteins involved in endogenous inflammatory responses and defense mechanisms developing postinjury. The present study analyzed the global gene expression profile in response to cryo-induced TBI...... at various time-points postlesion (6 h, 1 day and 4 days). The effects of injury, treatment, and injury-treatment interaction were observed. TBI alone rendered a large number of genes affected. Analysis of lesion and treatment interactions resulted in a clear effect of the interaction between injury and FGL......-treatment compared to injury and placebo-treatment. Genes affected by TBI alone included inflammation markers, protein kinases, ion channel members and growth factors. Genes encoding regulators of apoptosis, signal transduction and metabolism were altered by the interaction between FGL-treatment and TBI. FGL...

  13. Structural Elucidation of the Cell-Penetrating Penetratin Peptide in Model Membranes at the Atomic Level: Probing Hydrophobic Interactions in the Blood-Brain Barrier.

    Science.gov (United States)

    Bera, Swapna; Kar, Rajiv K; Mondal, Susanta; Pahan, Kalipada; Bhunia, Anirban

    2016-09-06

    Cell-penetrating peptides (CPPs) have shown promise in nonpermeable therapeutic drug delivery, because of their ability to transport a variety of cargo molecules across the cell membranes and their noncytotoxicity. Drosophila antennapedia homeodomain-derived CPP penetratin (RQIKIWFQNRRMKWKK), being rich in positively charged residues, has been increasingly used as a potential drug carrier for various purposes. Penetratin can breach the tight endothelial network known as the blood-brain barrier (BBB), permitting treatment of several neurodegenerative maladies, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, a detailed structural understanding of penetratin and its mechanism of action is lacking. This study defines structural features of the penetratin-derived peptide, DK17 (DRQIKIWFQNRRMKWKK), in several model membranes and describes a membrane-induced conformational transition of the DK17 peptide in these environments. A series of biophysical experiments, including high-resolution nuclear magnetic resonance spectroscopy, provides the three-dimensional structure of DK17 in different membranes mimicking the BBB or total brain lipid extract. Molecular dynamics simulations support the experimental results showing preferential binding of DK17 to particular lipids at atomic resolution. The peptide conserves the structure of the subdomain spanning residues Ile6-Arg11, despite considerable conformational variation in different membrane models. In vivo data suggest that the wild type, not a mutated sequence, enters the central nervous system. Together, these data highlight important structural and functional attributes of DK17 that could be utilized in drug delivery for neurodegenerative disorders.

  14. Effect of recombinant human brain natriuretic peptide-assisted interventional treatment on prognosis of acute myocardial infarction patients complicated with cardiogenic shock

    Institute of Scientific and Technical Information of China (English)

    Xi-Zhou Chen

    2016-01-01

    Objective:To analyze the effect of recombinant human brain natriuretic peptide-assisted interventional treatment on prognosis of acute myocardial infarction patients complicated with cardiogenic shock.Methods: A total of 112 cases of inpatients treated in Cardiology Department of our hospital from March 2013 to March 2015 were selected, all of whom had acute myocardial infarction within 12 hours of onset and received direct PCI treatment. They were divided into observation group and control group according to random number table, each group with 56 cases, control group received conventional interventional treatment and observation group received recombinant human brain natriuretic peptide-assisted interventional treatment. Then differences of regional myocardial deformability, myocardial enzyme spectrum indicators, brain natriuretic peptide and inflammatory factors, blood sugar and stress hormones as well as myocardial infarction prognosis-associated indexes, etc, between two groups after treatment were compared.Results:After treatment, LVEF, SRs, SRe and Sra levels of observation group were higher than those of control group, WMSI level was lower than that of control group; serum myocardial enzyme spectrum indicators CK, CK-MB, AST and LDH values were lower than those of control group; serum BNP, CRP, TNF-α and IL-6 levels were lower than those of control group; serum cortisol, growth hormone and glucagon levels were lower than those of control group, insulin level was higher than that of control group; FT3 and IGF-1 levels were higher than those of control group, sPLA2 and Hcy levels were lower than those of control group.Conclusion: Recombinant human brain natriuretic peptide-assisted interventional treatment for acute myocardial infarction patients complicated with cardiogenic shock can reduce myocardial function injury, protect normal myocardial function and optimize patients' long-term prognosis; it has active clinical significance.

  15. Diagnostic utility of C-reactive Protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Murakami Junji

    2011-06-01

    Full Text Available Abstract Introduction Discriminating acute lung injury (ALI or acute respiratory distress syndrome (ARDS from cardiogenic pulmonary edema (CPE using the plasma level of brain natriuretic peptide (BNP alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP in critically ill patients with pulmonary edema. Methods This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed. Results There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439 pg/mL and 119 (62-165 mg/L in ALI/ARDS, and 691 (416-1,194 pg/mL (p Conclusions Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.

  16. The relationship between N-terminal pro-brain natriuretic peptide and risk for hospitalization and mortality is curvilinear in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Corell, Pernille

    2007-01-01

    BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore, a clinica......BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore...... of doubling NT-proBNP on adjusted hazard ratios was 1.56 (95% CI 1.32-1.85) for mortality and 1.19 (95% CI 1.09-1.31) for hospitalization. We observed a curvilinear relationship between NT-proBNP and risk for mortality and hospitalization in the whole range of NT-proBNP. CONCLUSIONS: N-terminal pro-brain...... natriuretic peptide predicts risk for hospitalization and mortality. A simple algorithm indicates that every time NT-proBNP is doubled, estimated hazard ratio for death increases by a factor of 1.56 (56%) and by a factor of 1.19 (19%) for hospitalization. Finally, the relationship between NT-proBNP and risk...

  17. Effect of compound danshen dropping pill on angina as well as serum c-reactive protein (CRP) and brain natriuretic peptide (BNP)

    Institute of Scientific and Technical Information of China (English)

    Jing Ye

    2016-01-01

    Objective:To study the effect of Compound Danshen Dropping Pill on angina as well as serum C-reactive protein (CRP) and brain natriuretic peptide (BNP) so as to provide reference for clinical treatment.Methods: Patients with angina treated in our hospital from February 2010 to August 2015 were enrolled in this research. The effect of Compound Danshen Dropping Pill on angina as well as serum C reaction protein (CRP) and brain natriuretic peptide (BNP) were analyzed. 110 cases of healthy subjects receiving physical examination in our hospital during the same period were taken as control.Results: After treatment, the duration of angina significantly decreased, the frequency of angina pectoris attack significantly decreased, and serum inflammatory factors IL1, IL2 and IL6 as well as Hcy, TG, TC and LDL levels significantly decreased while HDL, folic acid and vitamin B12 levels significantly increased, and compared with before treatment, differences were with notable statistical significance. Conclusion: Compound Danshen Dropping Pill can effectively treat angina, which is related to its regulation of serum C-reactive protein, brain natriuretic peptide and inflammatory factor levels.

  18. Effect of recombinant human brain natriuretic peptide combined with sodium nitroprusside therapy on hemodynamics and cardiac in patients with acute decompensated heart failure

    Institute of Scientific and Technical Information of China (English)

    Qiao-Li Xing; Xian-Hong Ma; Lu Wang

    2016-01-01

    Objective:To evaluate the effect of recombinant human brain natriuretic peptide combined with sodium nitroprusside therapy on hemodynamics and cardiac function levels in patients with acute decompensated heart failure.Methods:A total of 118 patients with acute decompensated heart failure were randomly divided into observation group and the control group (n=59). Control group received clinical conventional therapy for heart failure, observation group received recombinant human brain natriuretic peptide combined with sodium nitroprusside therapy, and the differences in hemodynamics, cardiac function and circulation factor levels were compared between two groups after 12 hours of treatment. Results: After 12 hours of treatment, central venous pressure, right atrial pressure and pulmonary capillary wedge pressure values as well as circulating blood IL-6, hsCRP, ST2, NT-proBNP and cTnⅠlevels of observation group were lower than those of control group, and left heart GLS, GCS, GSRs, GSRe, GSRa, ROT and ROTR levels were higher than those of control group (P<0.05).Conclusions:Recombinant human brain natriuretic peptide combined with sodium nitroprusside therapy for patients with acute decompensated heart failure has significant advantages in optimizing hemodynamics, cardiac function and other aspects.

  19. Hypocretin and brain β-amyloid peptide interactions in cognitive disorders and narcolepsy

    Directory of Open Access Journals (Sweden)

    Yves A Dauvilliers

    2014-06-01

    Full Text Available Objective: To examine relationships between cerebrospinal fluid (CSF Alzheimer’ disease (AD biomarkers and hypocretin-1 levels in patients with cognitive abnormalities and hypocretin-deficient narcolepsy-cataplexy (NC, estimate diagnostic accuracy, and determine correlations with sleep disturbances. Background: Sleep disturbances are frequent in AD. Interactions between brain β-amyloid (Aβ aggregation and a wake-related neurotransmitter hypocretin have been reported in a mouse model of AD. Methods: Ninety-one cognitive patients (37 AD, 16 mild cognitive impairment – MCI that converts to AD, 38 other dementias and 15 elderly patients with NC were recruited. Patients were diagnosed blind to CSF results. CSF A42, total tau, ptau181, and hypocretin-1 were measured. Sleep disturbances were assessed with questionnaires in 32 cognitive patients. Results: Lower CSF Aβ42 but higher tau and P-tau levels were found in AD and MCI compared to other dementias. CSF hypocretin-1 levels were higher in patients with MCI due to AD compared to other dementias, with a similar tendency for patients with advanced AD. CSF hypocretin-1 was significantly and independently associated with AD/MCI due to AD, with an OR of 2.70 after full adjustment, exceeding that for Aβ42. Aβ42 correlated positively with hypocretin-1 levels in advanced stage AD. No association was found between sleep disturbances and CSF biomarkers. No patients with NC achieved pathological cutoffs for Aβ42, with respectively one and four patients with NC above tau and P-tau cutoffs and no correlations between hypocretin-1 and other biomarkers. Conclusions: Our results suggest a pathophysiological relationship between Aβ42 and hypocretin-1 in the AD process, with higher CSF hypocretin-1 levels in early disease stages. Further longitudinal studies are needed to validate these biomarker interactions and to determine the cause-effect relationship and the role of wake/sleep behavior in amyloid

  20. High circulating N-terminal pro-brain natriuretic peptide and tumor necrosis factor-α in mixed cryoglobulinemia

    Institute of Scientific and Technical Information of China (English)

    Alessandro Antonelli; Clodoveo Ferri; Silvia Martina Ferrari; Fabio Galetta; Ferdinando Franzoni; Gino Santoro; Salvatore De Marco; Emiliano Ghiri; Poupak Fallahi

    2009-01-01

    AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor α (TNF-α) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV).METHODS: Serum NTproBNP and TNF-α levels were assayed in 50 patients with MC+HCV, and in 50 sex-and age-matched controls.RESULTS: Cryoglobulinemic patients showed significantly higher mean NTproBNP and TNF-α levels than controls ( P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (χ~2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (χ~2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as the patients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (χ~2, P = 0.08).CONCLUSION: The study demonstrates high levels of circulating NTproBNP and TNF-α in MC+HCV patients.The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction.

  1. Elevated N-terminal pro-brain natriuretic peptide is associated with mortality in tobacco smokers independent of airflow obstruction.

    Directory of Open Access Journals (Sweden)

    Jason A Stamm

    Full Text Available BACKGROUND: Tobacco use is associated with an increased prevalence of cardiovascular disease. N-terminal pro-brain natiuretic peptide (NT-proBNP, a widely available biomarker that is associated with cardiovascular outcomes in other conditions, has not been investigated as a predictor of mortality in tobacco smokers. We hypothesized that NT-proBNP would be an independent prognostic marker in a cohort of well-characterized tobacco smokers without known cardiovascular disease. METHODS: Clinical data from 796 subjects enrolled in two prospective tobacco exposed cohorts was assessed to determine factors associated with elevated NT-proBNP and the relationship of these factors and NT-proBNP with mortality. RESULTS: Subjects were followed for a median of 562 (IQR 252-826 days. Characteristics associated with a NT-proBNP above the median (≥49 pg/mL were increased age, female gender, and decreased body mass index. By time-to-event analysis, an NT-proBNP above the median (≥49 pg/mL was a significant predictor of mortality (log rank p = 0.02. By proportional hazard analysis controlling for age, gender, cohort, and severity of airflow obstruction, an elevated NT-proBNP level (≥49 pg/mL remained an independent predictor of mortality (HR = 2.19, 95% CI 1.07-4.46, p = 0.031. CONCLUSIONS: Elevated NT-proBNP is an independent predictor of mortality in tobacco smokers without known cardiovascular disease, conferring a 2.2 fold increased risk of death. Future studies should assess the ability of this biomarker to guide further diagnostic testing and to direct specific cardiovascular risk reduction inventions that may positively impact quality of life and survival.

  2. A fast and sensitive enzyme immunoassay for brain natriuretic peptide based on micro-magnetic probes strategy.

    Science.gov (United States)

    Liu, Ruping; Liu, Juntao; Xie, Li; Wang, Mixia; Luo, Jinping; Cai, Xinxia

    2010-05-15

    In this paper, a simple, rapid and low-cost method for the high-sensitivity detection of brain natriuretic peptide (BNP) was developed, which adopted three amplification steps: (a) biotin-streptavidin amplification; (b) micro-magnetic probe amplification; (c) HRP (horseradish peroxidase) signal amplification. In the present strategy, the streptavidin-coated micro-magnetic particles (MMPs) were first conjugated with biotin-labeled capture antibody via the biotin-streptavidin interaction, which formed bio-functional micro-magnetic probes. Then, the analyte (antigen) is sandwiched by HRP-labeled antibody and capture antibody bound to MMPs. Finally, the HRP at the surface of sandwich structures catalytically oxidized the substrate and generated optical signals that reflected the amount of the target BNP. The influence of some important parameters such as the size of magnetic particles, the working concentration of HRP-labeled BNP antibody, the stability of magnetic probes, and the assay medium of serum BNP, etc. on the detection ability of present method was investigated in details. It is found that the detection limit of the proposed method could reach 10pg/mL for BNP, which is much lower than that of sandwich-type ELISA. Furthermore, this detection time for the proposed method just takes about 30min (two reaction steps and one wash step), which is faster than that of conventional sandwich-type ELISA (taking about 4h, three reaction steps and three wash steps). Inspired by these advantages, it is expected that this method can probably be applicable to the detection of other hormones and tumor markers that are present in only low concentrations within the human body.

  3. Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers

    Science.gov (United States)

    Gupta, Rajinder K.; Himashree, G.; Singh, Krishan; Soree, Poonam; Desiraju, Koundinya; Agrawal, Anurag; Ghosh, Dishari; Dass, Deepak; Reddy, Prassana K.; Panjwani, Usha; Singh, Shashi Bala

    2016-01-01

    Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility. PMID:26892302

  4. Non-linear Equation using Plasma Brain Natriuretic Peptide Levels to Predict Cardiovascular Outcomes in Patients with Heart Failure

    Science.gov (United States)

    Fukuda, Hiroki; Suwa, Hideaki; Nakano, Atsushi; Sakamoto, Mari; Imazu, Miki; Hasegawa, Takuya; Takahama, Hiroyuki; Amaki, Makoto; Kanzaki, Hideaki; Anzai, Toshihisa; Mochizuki, Naoki; Ishii, Akira; Asanuma, Hiroshi; Asakura, Masanori; Washio, Takashi; Kitakaze, Masafumi

    2016-11-01

    Brain natriuretic peptide (BNP) is the most effective predictor of outcomes in chronic heart failure (CHF). This study sought to determine the qualitative relationship between the BNP levels at discharge and on the day of cardiovascular events in CHF patients. We devised a mathematical probabilistic model between the BNP levels at discharge (y) and on the day (t) of cardiovascular events after discharge for 113 CHF patients (Protocol I). We then prospectively evaluated this model on another set of 60 CHF patients who were readmitted (Protocol II). P(t|y) was the probability of cardiovascular events occurring after >t, the probability on t was given as p(t|y) = -dP(t|y)/dt, and p(t|y) = pP(t|y) = αyβP(t|y), along with p = αyβ (α and β were constant); the solution was p(t|y) = αyβ exp(-αyβt). We fitted this equation to the data set of Protocol I using the maximum likelihood principle, and we obtained the model p(t|y) = 0.000485y0.24788 exp(-0.000485y0.24788t). The cardiovascular event-free rate was computed as P(t) = 1/60Σi=1,…,60 exp(-0.000485yi0.24788t), based on this model and the BNP levels yi in a data set of Protocol II. We confirmed no difference between this model-based result and the actual event-free rate. In conclusion, the BNP levels showed a non-linear relationship with the day of occurrence of cardiovascular events in CHF patients.

  5. One-year prognosis and the role of brain natriuretic peptide levels in patients with chronic cor pulmonale.

    Science.gov (United States)

    Park, So Young; Lee, Chang Youl; Kim, Changhwan; Jang, Seung Hun; Park, Yong Bum; Park, Sunghoon; Hwang, Yong Il; Lee, Myung Goo; Jung, Ki-Suck; Kim, Dong-Gyu

    2015-04-01

    Data on the clinical outcomes and role of brain natriuretic peptide (BNP) levels in patients with chronic cor pulmonale are limited. A total of 69 patients with chronic cor pulmonale, admitted for dyspnea (January 2007 to September 2011) to three university hospitals, were retrospectively reviewed. All of the patients had right ventricular (RV) dysfunction on echocardiography. The median age was 70.0 yr, and chronic obstructive pulmonary disease (40.6%) and tuberculosis-destroyed lung (TDL, 27.5%) were the leading causes of chronic cor pulmonale. At the 1-yr follow-up, the mortality rate was 15.9%, and the readmission rate was 53.7%; patients with TDL had higher mortality (31.6% vs. 10.0%; P=0.059) and readmission rates (78.9% vs. 43.8%; P=0.009) than those with non-TDL diseases. The area under the receiver operating characteristic curve for admission BNP levels to predict readmission was 0.788 (95% confidence interval [CI], 0.673-0.904), and the sensitivity and specificity of the cut-off value were 80.6% and 77.4%, respectively. In multivariate analysis, high admission BNP levels were a significant risk factor for subsequent readmission (hazard ratio, 1.049; 95% CI, 1.005-1.094). Additionally, admission BNP levels were well correlated with cardiac troponin I (r=0.558), and delta BNP also correlated with delta RV systolic pressure (n=25; r=0.562). In conclusion, among hospitalized patients with chronic cor pulmonale, admission high BNP levels are a significant risk factor for subsequent readmission. Therefore, more intensive monitoring and treatment are needed in patients with higher BNP levels.

  6. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage.

    Directory of Open Access Journals (Sweden)

    Ana Garcia-Alvarez

    Full Text Available INTRODUCTION: Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP in the early identification of cardiac involvement in Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-four patients divided into 3 groups--group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32, group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14, and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction 37 pg/ml were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27 ± 26 vs. 11 ± 8 pg/ml, p = 0.03. CONCLUSION/SIGNIFICANCE: In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

  7. Brain natriuretic peptide and copeptin levels are associated with cardiovascular disease in patients with chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    LI Xin; YANG Xin-chun; SUN Qian-mei; CHEN Xiang-dong; LI Yan-chun

    2013-01-01

    Background Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD).We explored the relationship between CVD,plasma brain natriuretic peptide (BNP) and copeptin in non-dialysis patients with chronic kidney disease (CKD).Methods BNP and copeptin were measured using ELISA in 86 non-dialysis patients with different degrees of CKD and in 20 control patients.The effects of BNP,copeptin levels and other biochemical indices on carotid ultrasound echocardiography and CVD history were determined using correlation analysis.Results BNP and copeptin levels were significantly higher in the CKD group than in the control group.Both indices increased progressively,in parallel with the decline in glomerular filtration rate (GFR).BNP levels were (184.25±65.18)ng/L in early phase CKD,(975.245±354.09) ng/L in middle phase CKD,and (1463.51±614.92) ng/ml in end phase CKD compared with levels of (101.56±42.76) ng/L in the control group (all P <0.01).Copeptin levels in the middle phase ((20.36±9.47) pmol/L) and end phase groups ((54.26±18.23) pmol/L were significantly higher than in the control group ((9.21±2.64) pmol/L; both P <0.01).There was no difference in copeptin levels between early phase CKD ((10.09±5.23)pmol/L) and control patients.Stepwise multiple regression analysis identified GFR,intima-media thickness (IMT),left ventricular hypertrophy (LVH),and previous history of CVD as independent risk factors for elevated BNP and copeptin levels.Conclusion BNP and copeptin appear to provide sensitive biological markers for the evaluation of atherosclerosis in non-dialysis patients with CKD.

  8. Effect of acupuncture at Foot-Yangming Meridian on gastric mucosal blood flow, gastric motility and brain-gut peptide

    Institute of Scientific and Technical Information of China (English)

    Ya-Ping Lin; Shou-Xiang Yi; Jie Yan; Xiao-Rong Chang

    2007-01-01

    AIM: To observe the effect of acupuncture at Foot-Yangming Meridian on gastric mucosal blood flow (GMBF),gastric motility and brain-gut peptide.METHODS: Sixty SD rats were randomly divided into 6 groups: normal control group, model group (group with gastric mucosal damage, GMD), Sibai group (with acupuncture at Sibai point + GMD), Tianshu group (with acupuncture at Tianshu point + GMD), Zusanli group (with acupuncture at Zusanli point + GMD) and nonacupoint group (with acupuncture at non-acupoint +GMD). The GMD model group was induced by infusing pure alcohol into gastric cavity. H2 Gas Clearance Test (HGCT) was used to measure GMBF, the frequency and amplitude of gastric motility were measured by the method of aerocyst, the content of brain-gut peptide in sinus ventriculi and bulbus medullae were detected by radioimmunoassay.RESULTS: Inhibitory effect of the frequency and amplitude of gastric motility were shown in model group,and the rates of frequency and amplitude changes were remarkably different from the normal control group (-19.41 ± 17.21 vs -4.71 ± 10.32, P < 0.05; -51.61 ±29.02 vs 1.81 ± 14.12, P < 0.01). In comparison with control group, the GMBF was 0.52 ± 0.161 mL vs 1.03± 0.255 mL per 100g tissue/min, P < 0.01, the content ofmotilin in sinus ventriculi and bulbus medullae was 63.04 ± 7.77 pg/mL vs 72.91 ± 8.42 pg/mL, P < 0.05and 50.96 ± 8.77 pg/mL vs 60.76 ± 8.05 pg/mL, P <0.05, but the content of somatostatin in sinus ventriculi and bulbus medullae was 179.85 ± 43.13 ng/g vs 90.54 ± 40.42 ng/g, P < 0.01 and 532.86 ± 122.58 ng/g vs 370.91 ± 76.29 ng/g, P < 0.05,respectively. In comparison with model group, the amplitude of gastric motility was 1.52 ± 20.13, -6.52 ± 23.31, 6.92 ± 25.21 vs -51.61 ± 29.02, P < 0.01 and GMBF was 0.694 ± 0.160mL vs 0.893 ± 0.210 mL, 1.038 ± 0.301 mL vs 0.52 ±0.161 mL per 100g tissue/min, P < 0.01, respectively in Tianshu, Sibai and Zusanli groups, the content of motilin in sinus

  9. 脑钠肽在儿科疾病的应用%The use of brain natriuretic peptide in pediatric diseases

    Institute of Scientific and Technical Information of China (English)

    章阿元

    2015-01-01

    脑钠肽(brain natriuretic peptide,BNP)是利钠肽家族中的一员,主要由心室肌细胞分泌,有利钠、利尿、扩张血管、抑制肾素-血管紧张素-醛固酮系统和交感神经系统活性作用.近年来,BNP检测多用于成人疾病领域,尤其是其在心血管疾病的临床应用已形成广泛共识.但目前BNP在儿科领域的相关研究及应用仍相对较少,本文就目前BNP在儿科领域的研究现状作一综述.%Brain natriuretic peptide (BNP) is one member of natriuretic peptide family and mainly secreted by ventricular myocardium.BNP has many functions such as natriuresis,diuresis,dilation of blood vessels,inhibition of renin-angiotensin-aldosterone system and sympathetic nervous system activity.In recent years,BNP analysis widely used in fields of adult diseases,especially in cardiovascular disease.But research and application of BNP in pediatrics diseases is still relatively small.This article reviewed biology character and the progress of BNP in pediatric diseases.

  10. Cocaine- and amphetamine-regulated transcript peptide (CART) in the brain of zebra finch, Taeniopygia guttata: Organization, interaction with neuropeptide Y, and response to changes in energy status.

    Science.gov (United States)

    Singh, Omprakash; Kumar, Santosh; Singh, Uday; Kumar, Vinod; Lechan, Ronald M; Singru, Praful S

    2016-10-15

    Cocaine- and amphetamine-regulated transcript (CART) has emerged as a potent anorectic agent. CART is widely distributed in the brain of mammals, amphibians, and teleosts, but the relevant information in avian brain is not available. In birds, CART inhibits food intake, whereas neuropeptide Y (NPY), a well-known orexigenic peptide, stimulates it. How these neuropeptides interact in the brain to regulate energy balance is not known. We studied the distribution of CART-immunoreactivity in the brain of zebra finch, Taeniopygia guttata, its interaction with NPY, and their response to dynamic energy states. CART-immunoreactive fibers were found in the subpallium, hypothalamus, midbrain, and brainstem. Conspicuous CART-immunoreactive cells were observed in the bed nucleus of the stria terminalis, hypothalamic paraventricular, supraoptic, dorsomedial, infundibular (IN), lateral hypothalamic, Edinger-Westphal, and parabrachial nuclei. Hypothalamic sections of fed, fasted, and refed animals were immunostained with cFos, NPY, and CART antisera. Fasting dramatically increased cFos- and NPY-immunoreactivity in the IN, followed by rapid reduction by 2 hours and restoration to normal fed levels 6-10 hours after refeeding. CART-immunoreactive fibers in IN showed a significant reduction during fasting and upregulation with refeeding. Within the IN, double immunofluorescence revealed that 94 ± 2.1% of NPY-immunoreactive neurons were contacted by CART-immunoreactive fibers and 96 ± 2.8% NPY-immunoreactive neurons expressed cFos during fasting. Compared to controls, superfused hypothalamic slices of fasted birds treated with CART-peptide showed a significant reduction (P CART in the brain of T. guttata may perform several functions, and has a particularly important role in the hypothalamic regulation of energy homeostasis. J. Comp. Neurol. 524:3014-3041, 2016. © 2016 Wiley Periodicals, Inc.

  11. Levels of vasoactive intestinal peptide,cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction

    Institute of Scientific and Technical Information of China (English)

    Chun-Hua Hang; Ji-Xin Shi; Jie-Shou Li; Wei Wu; Wei-Qin Li; Hong-Xia Yin

    2004-01-01

    AIM: To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction.METHODS: Rat models of focal traumatic brain injury were established by impact insult method, and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3, 12, 24, 72 h, and d 7. Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously. The levels of vasoactive intestinal peptide (VIP) in plasma, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VTP in jejunum. RESULTS: Gastric distension, delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12 h and 72 h, which peaked at postinjury 72 h. As compared with that of control group (247.8±29.5 ng/L), plasma VIP levels were significantly decreased at postinjury 3, 12 and 24 h (106.7±34.1 ng/L, 148.7±22.8 ng/L, 132.8±21.6 ng/L,respectively), but significantly increased at 72 h (405.0±29.8 ng/L) and markedly declined on d 7 (130.7±19.3 ng/L).However, Plasma levels CCK and CGRP were significantly increased through 3 h and 7 d following TBT (126-691% increases), with the peak at 72 h. Compared with control (VIP, 13.6±1.4 ng/g; CGRP, 70.6±17.7 ng/g); VIP and CGRP levels in jejunum were significantly increased at 3 h after TBI (VIP, 35.4±5.0 ng/g; CGRP, 103.8±22.1 ng/g), anddeclined gradually at 12 h and 24 h (VIP, 16.5±1.8 ng/g, 5.5±1.4 ng/g; CGRP, 34.9±9.7 ng/g, 18.5±7.7 ng/g), but were significantly increased again at 72 h (VIP, 48.7±9.5 ng/g; CGRP, 142.1±24.3 ng/g), then declined in various degrees on d 7 (VIP, 3.8±1

  12. Influence of recombinant human brain natriuretic peptide on myocardial enzymes, serum cardiac function indexes and oxygen metabolism of patients with open heart surgery with cardiopulmonary bypass

    Institute of Scientific and Technical Information of China (English)

    Shu-Tian Song; Ming Yang; Kun-Peng Li; Juan Xu; Chuan-Ming Bai; Ji-Wu Zhou

    2016-01-01

    Objective:To investigate and analyze the influence of recombinant human brain natriuretic peptide on myocardial enzymes, serum cardiac function indexes and oxygen metabolism of patients with open heart surgery with cardiopulmonary bypass.Methods:A total of 42 patients with open heart surgery with cardiopulmonary bypass during the period of June 2014 to January 2016 were randomly divided into the control group of 21 cases and the observation group of 21 cases. The control group was treated with routine postoperative treatment, and the observation group was treated with recombinant human brain natriuretic peptide on the basic treatment of control group, then the myocardial enzymes, serum cardiac function indexes and oxygen metabolism indexes of the two groups before the surgery and at 2 h, 12 h and 24 h after the surgery were respectively detected and compared.Results: There were no significant difference in myocardial enzymes, serum cardiac function indexes and oxygen metabolism indexes between two groups before the surgery (allP>0.05), while the myocardial enzymes and serum cardiac function indexes of the observation group at 2 h ,12 h and 24 h after the surgery were all significantly lower than those of control group, the oxygen metabolism indexes were significantly better than the levels of control group (allP<0.05).Conclusions:The recombinant human brain natriuretic peptide can effectively improve the myocardial enzymes, serum cardiac function indexes and oxygen metabolism state of patients with open heart surgery with cardiopulmonary bypass, and it has application value for the patients with the surgery is higher.

  13. Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex

    DEFF Research Database (Denmark)

    Olsen, M.H.; Hansen, T.W.; Christensen, M.K.

    2008-01-01

    BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated...... factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years. RESULTS: In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P

  14. Right and left cardiac function in HIV-infected patients investigated using radionuclide ventriculography and brain natriuretic peptide: a 5-year follow-up study

    DEFF Research Database (Denmark)

    Kristoffersen, U.S.; Lebech, A.M.; Gerstoft, J.

    2008-01-01

    ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF), as well as measurement of brain natriuretic peptide (BNP). Between July 2005 and January 2007, 63 patients (69%) agreed to participate in a follow-up study with a mean follow-up of 4.5 years. RESULTS: All patients had normal......, it seems that the improvement in immunocompetency and viral load has removed the problem of HIV-related cardiomyopathy. Although HAART has been suggested as a possible new cause of cardiomyopathy, we did not find any evidence of this Udgivelsesdato: 2008/3...

  15. Right and left cardiac function in HIV-infected patients investigated using radionuclide ventriculography and brain natriuretic peptide: a 5-year follow-up study

    DEFF Research Database (Denmark)

    Kristoffersen, U S; Lebech, A M; Gerstoft, J

    2008-01-01

    ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF), as well as measurement of brain natriuretic peptide (BNP). Between July 2005 and January 2007, 63 patients (69%) agreed to participate in a follow-up study with a mean follow-up of 4.5 years. RESULTS: All patients had normal......, it seems that the improvement in immunocompetency and viral load has removed the problem of HIV-related cardiomyopathy. Although HAART has been suggested as a possible new cause of cardiomyopathy, we did not find any evidence of this....

  16. Evaluation of proinflammatory cytokines and brain natriuretic peptide in patients with rheumatic heart diseases and coronary heart disease complicated by chronic heart insufficiency

    OpenAIRE

    2005-01-01

    Objective. To study proinflammatory cytokines and brain natriuretic peptide (BNP) in patients with rheumatic heart diseases (RHD) and coronary heart disease (CHD) complicated by chronic heart insufficiency (CHI). Material and methods. 54 pts with CHI (among them 16 with RHD and 38 with CHD with signs of CHI ofll-IV functional class according to NYHA that correspond to 11A-III stage according to N.D. Strazesko-V.H. \\frsilenko classification) and 30 healthy persons of control group were examine...

  17. Expression and Distribution of Glucagon-Like Peptide-1 Receptor mRNA, Protein and Binding in the Male Nonhuman Primate (Macaca mulatta) Brain

    OpenAIRE

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) is released from endocrine L-cells lining the gut in response to food ingestion. However, GLP-1 is also produced in the nucleus of the solitary tract, where it acts as an anorectic neurotransmitter and key regulator of many autonomic and neuroendocrine functions. The expression and projections of GLP-1-producing neurons is highly conserved between rodent and primate brain, although a few key differences have been identified. The GLP-1 receptor (GLP-1R) has been...

  18. N-terminal pro-brain natriuretic peptide levels and short term prognosis in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Vandanapu Naveen

    2015-01-01

    Full Text Available Background: Sparse published data are available regarding the prognostic importance of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP in patients with acute ischemic stroke. Materials and Methods: We prospectively studied 74 consecutive patients presenting with acute ischemic stroke within 24 hours of onset. All of them underwent laboratory and imaging evaluation and were treated as per guidelines. In all subjects, plasma NT-proBNP levels were measured at initial admission and again on day 7. Results: Their mean age was 54 ± 13.5years; there were 49 males; 18 (24% patients died during the hospital stay. A statistically significant negative correlation between log NT-proBNP and Glasgow coma scale (GCS score (P < 0.001; and a significant positive correlation between log NT-proBNP and National Institutes of Health Stroke Scale (NIHSS score (P < 0.001 were observed. Baseline log NT-proBNP levels were higher among non-survivors compared with survivors (6.7 ± 0.47 vs. 5.37 ± 0.62; P = 0.06; day 7 log NT-proBNP levels were significantly higher in non-survivors compared with survivors (7.3 ± 0.26 vs. 4.5 ± 0.4; P = 0.000. In survivors, there was a statistically significant decline in log NT-proBNP levels from baseline to day 7 (5.3710 ± 0.620 vs. 4.5320 ± 0.451; P < 0.001. In contrast, among non-survivors, log NT-proBNP levels showed a statistically significant increase from baseline to day 7 (4.5322 ± 0.451 vs. 7.2992 ± 0.263; P < 0.001. On receiver operator characteristic curve (ROC analysis, at a cut-off value of ≥ 6.0661, log NT-proBNP had a sensitivity and specificity of 98.2 and 88.9, respectively, in predicting death. Conclusions: Plasma log NT-pro-BNP level appears to be a useful biological marker for predicting in-hospital mortality inpatients presenting with acute ischemic stroke.

  19. Prolongation of life in rats with malignant glioma by intranasal siRNA/drug codelivery to the brain with cell-penetrating peptide-modified micelles.

    Science.gov (United States)

    Kanazawa, Takanori; Morisaki, Kazuki; Suzuki, Shohei; Takashima, Yuuki

    2014-05-01

    New therapeutic strategies are required to develop candidate drugs and ensure efficient delivery of these drugs to the brain and the central nervous system (CNS). Small interfering RNA (siRNA)-based therapies have been investigated as potential novel approaches for the treatment of brain disorders. Previously, we showed that Tat, a cell-penetrating peptide derived from HIV-Tat, and the modified block copolymers (MPEG-PCL-Tat) can form stable complexes with siRNA or can be loaded with an anticancer drug and efficiently deliver the drugs to the brain tissue via intranasal delivery. In this study, to develop a novel, efficient, and safe therapeutic strategy for managing brain disorders, we used MPEG-PCL-Tat micelles with a nose-to-brain delivery system to investigate its therapeutic effects on a rat model of malignant glioma using siRNA with a Raf-1 (siRaf-1)/camptothecin (CPT) codelivery system. MPEG-PCL-Tat and CPT-loaded MPEG-PCL-Tat can form a stable complex with siRNA with a particle size from 60 to 200 nm and a positive charge at N/P ratios up to 5. Additionally, MPEG-PCL-Tat/siRaf-1 and CPT-loaded MPEG-PCL-Tat/siRaf-1 have fostered cell death in rat glioma cells after the high cellular uptake of siRaf-1/drug by the MPEG-PCL-Tat carrier. Furthermore, compared to the unloaded MPEG-PCL-Tat/siRaf-1 complex, a CPT-loaded MPEG-PCL-Tat/siRaf-1 complex achieved the high therapeutic effect because of the additive effects of CPT and siRaf-1. These results indicate that drug/siRNA codelivery using MPEG-PCL-Tat nanomicelles with nose-to-brain delivery is an excellent therapeutic approach for brain and CNS diseases.

  20. Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood–brain barrier in rats

    Directory of Open Access Journals (Sweden)

    Valiante S

    2015-03-01

    Full Text Available Salvatore Valiante,1,* Annarita Falanga,2,3,* Luisa Cigliano,1 Giuseppina Iachetta,1 Rosa Anna Busiello,1 Valeria La Marca,1 Massimiliano Galdiero,4 Assunta Lombardi,1 Stefania Galdiero1,2 1Department of Biology, 2Department of Pharmacy, 3DFM Scarl, University of Naples Federico II, 4Department of Experimental Medicine, II University of Naples, Naples, Italy *These authors contributed equally to this paper and are considered joint first authors Abstract: Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood–brain barrier (BBB. In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human diseases. Keywords: drug delivery, neurons, astrocytes, blood–brain barrier, peptide

  1. The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Hiroko Sano

    2015-05-01

    Full Text Available The coordination of growth with nutritional status is essential for proper development and physiology. Nutritional information is mostly perceived by peripheral organs before being relayed to the brain, which modulates physiological responses. Hormonal signaling ensures this organ-to-organ communication, and the failure of endocrine regulation in humans can cause diseases including obesity and diabetes. In Drosophila melanogaster, the fat body (adipose tissue has been suggested to play an important role in coupling growth with nutritional status. Here, we show that the peripheral tissue-derived peptide hormone CCHamide-2 (CCHa2 acts as a nutrient-dependent regulator of Drosophila insulin-like peptides (Dilps. A BAC-based transgenic reporter revealed strong expression of CCHa2 receptor (CCHa2-R in insulin-producing cells (IPCs in the brain. Calcium imaging of brain explants and IPC-specific CCHa2-R knockdown demonstrated that peripheral-tissue derived CCHa2 directly activates IPCs. Interestingly, genetic disruption of either CCHa2 or CCHa2-R caused almost identical defects in larval growth and developmental timing. Consistent with these phenotypes, the expression of dilp5, and the release of both Dilp2 and Dilp5, were severely reduced. Furthermore, transcription of CCHa2 is altered in response to nutritional levels, particularly of glucose. These findings demonstrate that CCHa2 and CCHa2-R form a direct link between peripheral tissues and the brain, and that this pathway is essential for the coordination of systemic growth with nutritional availability. A mammalian homologue of CCHa2-R, Bombesin receptor subtype-3 (Brs3, is an orphan receptor that is expressed in the islet β-cells; however, the role of Brs3 in insulin regulation remains elusive. Our genetic approach in Drosophila melanogaster provides the first evidence, to our knowledge, that bombesin receptor signaling with its endogenous ligand promotes insulin production.

  2. Method for measurement of the blood-brain barrier permeability in the perfused mouse brain: application to amyloid-beta peptide in wild type and Alzheimer's Tg2576 mice.

    Science.gov (United States)

    LaRue, Barbra; Hogg, Elizabeth; Sagare, Abhay; Jovanovic, Suzana; Maness, Lawrence; Maurer, Calvin; Deane, Rashid; Zlokovic, Berislav V

    2004-09-30

    The role of transport exchanges of neuroactive solutes across the blood-brain barrier (BBB) is increasingly recognized. To take full advantage of genetically altered mouse models of neurodegenerative disorders for BBB transport studies, we adapted a brain perfusion technique to the mouse. During a carotid brain perfusion with a medium containing sheep red blood cells and mock plasma, the physiological parameters in the arterial inflow, regional cerebral blood flow (14C-iodoantipyrine autoradiography), ultrastructural integrity of the tissue, barrier to lanthanum, brain water content, energy metabolites and lactate levels remain unchanged. Amyloid-beta peptides (Abeta) were iodinated by lactoperoxidase method. Non-oxidized mono-iodinated Abeta monomers were separated by HPLC (as confirmed by MALDI-TOF spectrometry) and used in transport measurements. Transport of intact 125I-Abeta40 across the BBB was time- and concentration-dependent in contrast to negligible 14C-inulin uptake. In 5-6 months old Alzheimer's Tg2576 mice, Abeta40 BBB transport was increased by >eight-fold compared to age-matched littermate controls, and was mediated via the receptor for advanced glycation endproducts. We conclude the present arterial brain perfusion method provides strictly controlled environment in cerebral microcirculation suitable for examining transport of rapidly and slowly penetrating molecules across the BBB in normal and transgenic mice.

  3. Gene delivery to brain cells with apoprotein E derived peptide conjugated to polylysine (apoEdp-PLL).

    Science.gov (United States)

    Mousazadeh, Mohammad; Palizban, Abbasali; Salehi, Rasool; Salehi, Mansoor

    2007-04-01

    A promising strategy to carry genetic material to brain cells either in vitro or in vivo is using the LDL receptor (LDLr) on blood-brain barrier. LDLr naturally help to low density lipoproteins (LDL(S)) transporting across the BBB by endocytosis. Here we present the idea of using the LDLr-mediated pathway for transporting genetic material to brain cells. A tandem dimer Sequence of apoprotein-E (apoE) (141-150) conjugated to polylysine sequence was used as a novel DNA Delivery vector for transfecting of brain cells either in vitro or in vivo. DNA condensation occurs with this vector because electrostatic interaction between DNA and polylysine. The vector favors to protection of DNA from enzymatic degradation and also helps to DNA carrying in blood stream to reach BBB and transport it to brain cells and eventually help DNA expression in target cells. These results suggest a novel gene delivery vector for gene therapy of brain disease.

  4. Neuropeptide Y receptor binding sites in rat brain: differential autoradiographic localizations with sup 125 I-peptide YY and sup 125 I-neuropeptide Y imply receptor heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Lynch, D.R.; Walker, M.W.; Miller, R.J.; Snyder, S.H. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1989-08-01

    Neuropeptide Y (NPY) receptor binding sites have been localized in the rat brain by in vitro autoradiography using picomolar concentrations of both 125I-NPY and 125I-peptide YY (PYY) and new evidence provided for differentially localized receptor subtypes. Equilibrium binding studies using membranes indicate that rat brain contains a small population of high-affinity binding sites and a large population of moderate-affinity binding sites. 125I-PYY (10 pM) is selective for high-affinity binding sites (KD = 23 pM), whereas 10 pM 125I-NPY labels both high- and moderate-affinity sites (KD = 54 pM and 920 pM). The peptide specificity and affinity of these ligands in autoradiographic experiments match those seen in homogenates. Binding sites for 125I-PYY are most concentrated in the lateral septum, stratum oriens, and radiatum of the hippocampus, amygdala, piriform cortex, entorhinal cortex, several thalamic nuclei, including the reuniens and lateral posterior nuclei, and substantia nigra, pars compacta, and pars lateralis. In the brain stem, 125I-PYY sites are densest in a variety of nuclei on the floor of the fourth ventricle, including the pontine central grey, the supragenual nucleus, and the area postrema. 125I-NPY binding sites are found in similar areas, but relative levels of NPY binding and PYY binding differ regionally, suggesting differences in sites labeled by the two ligands. These receptor localizations resemble the distribution of endogenous NPY in some areas, but others, such as the hypothalamus, contain NPY immunoreactivity but few binding sites.

  5. Scorpion venom heat-resistant peptide (SVHRP enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Scorpion venom heat-resistant peptide (SVHRP is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2'-dexoxyuridine (BrdU-positive cells, BrdU-positive/neuron-specific nuclear protein (NeuN-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM-positive immature neurons in the subventricular zone (SVZ and subgranular zone (SGZ of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF but not nerve growth factor (NGF or glial cell line-derived neurotrophic factor (GDNF was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values

  6. Scorpion venom heat-resistant peptide (SVHRP) enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Wang, Tao; Wang, Shi-Wei; Zhang, Yue; Wu, Xue-Fei; Peng, Yan; Cao, Zhen; Ge, Bi-Ying; Wang, Xi; Wu, Qiong; Lin, Jin-Tao; Zhang, Wan-Qin; Li, Shao; Zhao, Jie

    2014-01-01

    Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2'-dexoxyuridine (BrdU)-positive cells, BrdU-positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP.

  7. Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood–brain barrier in rats

    Science.gov (United States)

    Valiante, Salvatore; Falanga, Annarita; Cigliano, Luisa; Iachetta, Giuseppina; Busiello, Rosa Anna; La Marca, Valeria; Galdiero, Massimiliano; Lombardi, Assunta; Galdiero, Stefania

    2015-01-01

    Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood–brain barrier (BBB). In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human diseases. PMID:25792823

  8. Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood-brain barrier in rats.

    Science.gov (United States)

    Valiante, Salvatore; Falanga, Annarita; Cigliano, Luisa; Iachetta, Giuseppina; Busiello, Rosa Anna; La Marca, Valeria; Galdiero, Massimiliano; Lombardi, Assunta; Galdiero, Stefania

    2015-01-01

    Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood-brain barrier (BBB). In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human diseases.

  9. A multimodal Pepstatin A peptide-based nanoagent for the molecular imaging of P-glycoprotein in the brains of epilepsy rats.

    Science.gov (United States)

    Yu, Xiangrong; Wang, Jianhong; Liu, Jiansheng; Shen, Shun; Cao, Zhonglian; Pan, Jiawei; Zhou, Shuyi; Pang, Zhiqing; Geng, Daoying; Zhang, Jun

    2016-01-01

    Regional overexpression of the multidrug transporter P-glycoprotein (P-gp) in epileptic brain tissues may lower antiepileptic drugs concentrations at the target site and contribute to pharmacoresistance in refractory epilepsy. However, few techniques are available to quantitate the level of P-gp expression noninvasively in vivo. In this study, we developed a nanoagent by conjugating superparamagnetic iron oxide nanoparticles with a near infrared probe and the targeting element Pepstatin A, a peptide with specific affinity for P-gp. In a rat model of epilepsy, the nanoagent was readily and selectively accumulated within epileptogenic cerebral regions, which were detectable by both magnetic resonance imaging and optical imaging modalities. This P-gp-targeted nanoagent could be used not only in the molecular imaging of P-gp expression changes in seizure-induced regional, understanding the mechanisms of P-gp disorders, and the prediction of refractory epilepsy, but also in targeted therapies with P-gp modulators.

  10. Effects of body mass index and age on N-terminal pro brain natriuretic peptide are associated with glomerular filtration rate in chronic heart failure patients

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Kistorp, Caroline N

    2007-01-01

    BACKGROUND: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure...... (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR. METHODS: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using...... multiple linear regression models. RESULTS: Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P

  11. The usefulness of brain natriuretic peptide level in diagnosis and prognosis of patients admitted to critical care unit with shortness of breath

    Directory of Open Access Journals (Sweden)

    Yazan Abdeen

    2015-01-01

    Full Text Available Background: Brain Natriuretic Peptide (BNP is a polypeptide secreted by the ventricles as a response to cardio-myocyte stretching. Due to its cardiac origin and correlation with volume overload it has been successfully used for a long time in diagnosing and prognosticating Cardiogenic Pulmonary Edema. Materials and Methods: In this retrospective cohort study, an attempt was made to observe any correlation between admission BNP levels with APACHE II scores and length of ICU stay, in patients admitted with dyspnea to the ICU of a community based hospital. Results/Conclusion: This study showed no significant correlation between length of stay in an ICU and admission BNP levels in dyspneic patients. Independent variables such as age and gender failed to show any coorelation either.

  12. Changes in the brain and plasma Aβ peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Izco, M; Martínez, P; Corrales, A; Fandos, N; García, S; Insua, D; Montañes, M; Pérez-Grijalba, V; Rueda, N; Vidal, V; Martínez-Cué, C; Pesini, P; Sarasa, M

    2014-03-28

    Double transgenic mice expressing mutant amyloid precursor protein (APPswe) and mutant presenilin 1 (PS1dE9) are a model of Alzheimer-type amyloidosis and are widely used in experimental studies. In the present work, the relationships between brain and plasma amyloid-β peptide (Aβ) levels and cognitive impairments were examined in male APPswe/PS1dE9 double transgenic mice at different ages. When compared with non-transgenic littermates, APPswe/PS1dE9 mice exhibited significant learning deficits from the age of 6months (M6), which were aggravated at later stages of life (M8 and M12). Sporadic brain amyloid plaques were observed in mice as early as M3 and progressively increased in number and size up to M12. A similar increase was observed in brain insoluble Aβ levels as assessed by enzyme-linked immunosorbent assay (ELISA). In particular, the levels of brain insoluble Aβ peptides rose steeply from M4 to M6. Interestingly, this pronounced amyloid deposition was accompanied by a temporary fall in the concentration of brain soluble and membrane-bound Aβ peptides at M6 that rose again at M8 and M12. The plasma levels of Aβ40 and Aβ42 decreased with advancing age up to M8, when they stabilized at M12. This decrease in plasma Aβ levels coincided with the observed increase in insoluble brain Aβ levels. These results could be useful for developing plasma Aβ levels as possible biomarkers of the cerebral amyloidosis and provide advances in the knowledge of the Aβ peptide biochemical changes that occur in the brain of Alzheimer's disease patients.

  13. Human anti-Aβ IgGs target conformational epitopes on synthetic dimer assemblies and the AD brain-derived peptide.

    Directory of Open Access Journals (Sweden)

    Alfred T Welzel

    Full Text Available Soluble non-fibrillar assemblies of amyloid-beta (Aβ and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer's disease (AD. Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ's conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody's nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody's lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted.

  14. Human Anti-Aβ IgGs Target Conformational Epitopes on Synthetic Dimer Assemblies and the AD Brain-Derived Peptide

    Science.gov (United States)

    Welzel, Alfred T.; Williams, Angela D.; McWilliams-Koeppen, Helen P.; Acero, Luis; Weber, Alfred; Blinder, Veronika; Mably, Alex; Bunk, Sebastian; Hermann, Corinna; Farrell, Michael A.; Ehrlich, Hartmut J.; Schwarz, Hans P.; Walsh, Dominic M.; Solomon, Alan; O’Nuallain, Brian

    2012-01-01

    Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer’s disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ’s conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody’s nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody’s lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted. PMID:23209707

  15. Human anti-Aβ IgGs target conformational epitopes on synthetic dimer assemblies and the AD brain-derived peptide.

    Science.gov (United States)

    Welzel, Alfred T; Williams, Angela D; McWilliams-Koeppen, Helen P; Acero, Luis; Weber, Alfred; Blinder, Veronika; Mably, Alex; Bunk, Sebastian; Hermann, Corinna; Farrell, Michael A; Ehrlich, Hartmut J; Schwarz, Hans P; Walsh, Dominic M; Solomon, Alan; O'Nuallain, Brian

    2012-01-01

    Soluble non-fibrillar assemblies of amyloid-beta (Aβ) and aggregated tau protein are the proximate synaptotoxic species associated with Alzheimer's disease (AD). Anti-Aβ immunotherapy is a promising and advanced therapeutic strategy, but the precise Aβ species to target is not yet known. Previously, we and others have shown that natural human IgGs (NAbs) target diverse Aβ conformers and have therapeutic potential. We now demonstrate that these antibodies bound with nM avidity to conformational epitopes on plate-immobilized synthetic Aβ dimer assemblies, including synaptotoxic protofibrils, and targeted these conformers in solution. Importantly, NAbs also recognized Aβ extracted from the water-soluble phase of human AD brain, including species that migrated on denaturing PAGE as SDS-stable dimers. The critical reliance on Aβ's conformational state for NAb binding, and not a linear sequence epitope, was confirmed by the antibody's nM reactivity with plate-immobilized protofibrills, and weak uM binding to synthetic Aβ monomers and peptide fragments. The antibody's lack of reactivity against a linear sequence epitope was confirmed by our ability to isolate anti-Aβ NAbs from intravenous immunoglobulin using affinity matrices, immunoglobulin light chain fibrils and Cibacron blue, which had no sequence similarity with the peptide. These findings suggest that further investigations on the molecular basis and the therapeutic/diagnostic potential of anti-Aβ NAbs are warranted.

  16. Association between resting heart rate and N-terminal pro-brain natriuretic peptide in a community-based population study in Beijing

    Directory of Open Access Journals (Sweden)

    Cao R

    2014-12-01

    Full Text Available Ruihua Cao, Yongyi Bai, Ruyi Xu, Ping Ye Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, People’s Republic of China Background: N-terminal pro-brain natriuretic peptide (NT-proBNP is associated with an increased risk of cardiac insufficiency, which possibly leads to heart failure. However, the relationship between resting heart rate and NT-proBNP is unclear.Objective: This study focuses on this relativity between resting heart rate and plasma NT-proBNP levels in a surveyed community-based population.Methods: We evaluated the relativity between resting heart rate and plasma levels of NT-proBNP in 1,567 participants (mean age 61.0 years, range 21–96 years from a community-based population in Beijing, People’s Republic of China.Results: In patients with high resting heart rate (≥75 beats/min, NT-proBNP was higher than in those having low resting heart rate (<75 beats/min. In multiple linear stepwise regression analysis, plasma NT-proBNP was associated with resting heart rate (partial correlation coefficient, 0.82; 95% confidence interval, 0.18–1.51; P=0.011. A subsequent subgroup analysis revealed that the association between resting heart rate and plasma NT-proBNP was strengthened in subjects over 60 years old (partial correlation coefficient 1.28; 95% confidence interval, 0.49–2.36; P=0.031; while the relativity between resting heart rate and plasma NT-proBNP was not emerged in the younger subgroup (<60 years old.Conclusions: Resting heart rate was associated with plasma NT-proBNP in the elderly, which indicated a relationship between resting heart rate and cardiac function damage. Keywords: resting heart rate, N-terminal pro-brain natriuretic peptide, epidemiology, cardiac function, relationship

  17. Relationship between the severity of mitral regurgitation, left ventricular dysfunction and plasma brain natriuretic peptide level: An observational strain imaging study

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Elbey

    2012-12-01

    Full Text Available Objectives: The aim of the this study was to investigatethe relationship between the degree of mitral regurgitation(MR, left ventricular (LV dysfunction determined bystrain (S/strain rate (SR imaging and plasma brain natriureticpeptide (BNP levels.Materials and methods: This is an observational crosssectionalstudy which included 31 consecutive patients(15[48.4%] male who had applied to our outpatient clinicsand diagnosed as mitral regurgitation and 25 (12[48.0%] male healthy persons as control subjects. Themitral regurgitation patients were divided into two groups:those with moderate MR (n=14[45.2%] and those withsevere MR (n=17[54.8%], and maximum strain / strainrate measurements of left ventricular wall segments andplasma brain natriuretic peptide levels were determined inthese two groups and controls.Results: S/SR values of all wall segments of left ventriclewere found to be decreased in patient with severe MRwhen compared with the control subjects and patientswith moderate MR (p<0.001.Conclusions: Although left ventricle functions with conventionalechocardiography in patients with mitral valveregurgitation were normal, subclinic deteriorations ofleft ventricle were detected in patients with severe mitralvalve regurgitation. J Clin Exp Invest 2012; 3 (4: 451-456Key words: strain/strain rate, echocardiography, mitralregurgitation, left ventricular functions

  18. [EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION].

    Science.gov (United States)

    Meshchaninov, V N; Tkachenko, E L; Zharkov, S V; Gavrilov, I V; Katyreva, Iu E

    2015-01-01

    We've estimated the cellular and metabolic part of geroprophylactic effects of short synthetic tripeptides vesugen and pinealon for correction of the biological age. 32 people (18 men, 12 women) aged 41-83 years with polymorbidity and the organic brain syndrome in remission participated in the study. The preparations of "Pinealon" and "Vesugen" have had the significant anabolic effect. They have improved the activity of the Central nervous system and other vital organs, which slows the rate of aging by biological age indicators. Vesugen has demonstrated more visible geroprophylactic effect than Pinealon. At the same time we've found the prooxidant activity through chemiluminescence. Decrease of markers CD34+ positive hematopoietic polypotent cells in blood has shown significant inhibition of hemopoiesis. Apparently, the cells have not been involved in the adaptive reactions. Pinealon and Vesugen haven't affected the degree of chromatin condensation, so they are safe on nuclear genetic level. This property should be studied in future. In geriatric practice, we recommend to apply the peptides Pinealon and Vesugen as geroprotectors anabolic neuroprotective and no antioxidant type for reducing the rate of aging in patients with the organic brain syndrome vascular and/or traumatic genesis.

  19. Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS.

    Science.gov (United States)

    Gao, Bo; Vavricka, Stephan R; Meier, Peter J; Stieger, Bruno

    2015-07-01

    Organic anion transporting polypeptides (OATPs) are polyspecific organic anion transporters, which are expressed in the blood-brain barrier, the choroid plexus, and other organs. The physiologic function of OATPs in extrahepatic tissues remains ambiguous. In rat retina, members of the OATP family are expressed. We therefore investigated the human retina for the expression of OATP1A2 and OATP2B1 and extended the study to human brain. Furthermore, we searched for peptide neurotransmitters as novel OATP substrates. OATP1A2 displayed a broad expression pattern in human retina as assessed by immunofluorescence localization. It is expressed in photoreceptor bodies and somas of amacrine cells. OATP1B2 expression is restricted to the inner nuclear layer and to the inner plexiform layer. Using paraffin sections from human cortex, cerebellum, and hippocampus, OATP1A2 was localized to neurons and neuronal processes, while OATP2B1 is expressed in endothelial cells of brain capillaries. Substance P and vasoactive intestinal peptide were identified as substrates for OATP1A2 and OATP2B1. Double-labeling immunofluorescence of human retina demonstrated the presence of substance P and of vasoactive intestinal peptides in neurons expressing OATP1A2 and OATP2B1, respectively. The expression of OATP1A2 and OATP2B1 in retinal neurons implies a role of these transporters in the reuptake of peptide neurotransmitters released from retinal neurons. The abundant expression of OATP1A2 in brain neurons points to the possibility that OATP1A2 could be involved in the homeostasis of neurosteroids. The high expression of OATP2B1 in brain capillaries supports an important function of OATPs in substance penetration across the blood-brain barrier.

  20. A quantitative in-vivo MR imaging study of brain dehydration in diabetic rats and rats treated with peptide hormones.

    Science.gov (United States)

    Haraldseth, O; Jones, R A; Skottner, A

    1997-01-01

    The main aim of the study was to evaluate the combination of quantitative diffusion, T2 and Magnetisation Transfer Imaging of brain water homeostasis using untreated diabetes as an animal model of brain dehydration. In addition, experimental groups of diabetic rats treated with insulin and insulin-like growth factor (IGF-I) and normal rats treated with IGF-I and growth hormone were studied using the same MR imaging protocol. Untreated diabetes caused weight reduction and an increase in water intake, indicating a general body dehydration linked to chronic blood hyperosmolarity. In the investigated cortical gray matter untreated diabetes caused a significant reduction in the apparent diffusion coefficient of water (ADC) and an increase in T2 relaxtivity (R2) when compared to a control group. No significant changes were observed for the calculated magnetisation transfer parameters Kfor and T1sat. Both ADC and R2 normalized after appropriate insulin treatment whereas only ADC was normalized after IGF-I treatment. IGF-I treatment of normal rats caused significantly higher rate of increase in body weight compared to normal controls. There were, however, no significant changes in ADC, R2 nor the magnetisation transfer parameters measured in the cortical gray matter of the IGF-I treated normal rats. In conclusion, we found that changes in brain water homeostasis during diabetes were detected by quantitative MR imaging, and that the dehydration induced by diabetes was normalized by insulin treatment but not by IGF-I.

  1. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Y T [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Tian, W M [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Yu, X [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Cui, F Z [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Hou, S P [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing, 100054 (China); Xu, Q Y [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing, 100054 (China); Lee, In-Seop [Institute of Physics and Applied Physics, and Atomic-scale Surface Science Research Center, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2007-09-15

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue.

  2. Influence of training habits on exercise-induced changes in plasma atrial and brain natriuretic peptide and urinary excretion of aquaporin-2 in healthy man.

    Science.gov (United States)

    Bentzen, H; Pedersen, R S; Nyvad, O; Pedersen, E B

    2002-01-01

    The purpose of this study was to quantify the influence of training habits on the changes in plasma atrial natriuretic peptide (ANP), plasma brain natriuretic peptide (BNP) and urine aquaporin-2 (u-AQP2) during exercise by studying trained and untrained healthy subjects. Eleven trained subjects (7 males, 4 females) and 10 untrained subjects (8 males, 2 females) performed a maximal aerobic exercise test. ANP and BNP were determined every 3 min and at maximum exercise by radioimmunoassay (RIA), and u-AQP2 was determined before and after the exercise test by RIA. The absolute increase in ANP during exercise was higher in the trained subjects (trained subjects: 5.6 pmol/L; untrained subjects: 2.4 pmol/L, p exercise was the same in the two groups (trained subjects: 0.5 pmol/L; untrained subjects: 0.6 pmol/L, NS) and tended to correlate positively with resting BNP in the trained subjects (p = 0.07). Exercise did not change u-AQP2 excretion in either trained subjects (rest: 372 ng/mmol creatinine; exercise: 314 ng/mmol creatinine, NS) or untrained subjects (rest: 263 ng/mmol creatinine; exercise: 338 ng/mmol creatinine, NS). The absolute increase in ANP during exercise was higher in trained subjects than in untrained subjects and was positively correlated to ANP at rest. This might reflect the normal cardiovascular adaptation to exercise. The increase in BNP during exercise was unrelated to training habits. Training habits did not affect the u-AQP2 excretion during exercise.

  3. Urine albumin/creatinine ratio, high sensitivity C-reactive protein and N-terminal pro brain natriuretic peptide--three new cardiovascular risk markers--do they improve risk prediction and influence treatment?

    DEFF Research Database (Denmark)

    Olsen, Michael H; Sehestedt, Thomas; Lyngbaek, Stig

    2010-01-01

    In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt-proBNP), ......In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt...... death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified...

  4. The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

    Science.gov (United States)

    Herminghuysen, D; Cook, C; Thompson, H; Bostick, D; Lee, F; Stokes, L; Hilton, C; Prasad, C

    1994-04-01

    Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

  5. Exendin-4 induced glucagon-like peptide-1 receptor activation reverses behavioral impairments of mild traumatic brain injury in mice.

    Science.gov (United States)

    Rachmany, Lital; Tweedie, David; Li, Yazhou; Rubovitch, Vardit; Holloway, Harold W; Miller, Jonathan; Hoffer, Barry J; Greig, Nigel H; Pick, Chaim G

    2013-10-01

    Mild traumatic brain injury (mTBI) represents a major and increasing public health concern and is both the most frequent cause of mortality and disability in young adults and a chief cause of morbidity in the elderly. Albeit mTBI patients do not show clear structural brain defects and, generally, do not require hospitalization, they frequently suffer from long-lasting cognitive, behavioral, and emotional problems. No effective pharmaceutical therapy is available, and existing treatment chiefly involves intensive care management after injury. The diffuse neural cell death evident after mTBI is considered mediated by oxidative stress and glutamate-induced excitotoxicity. Prior studies of the long-acting GLP-1 receptor agonist, exendin-4 (Ex-4), an incretin mimetic approved for type 2 diabetes mellitus treatment, demonstrated its neurotrophic/protective activity in cellular and animal models of stroke, Alzheimer's and Parkinson's diseases, and, consequent to commonalities in mechanisms underpinning these disorders, Ex-4 was assessed in a mouse mTBI model. In neuronal cultures in this study, Ex-4 ameliorated H2O2-induced oxidative stress and glutamate toxicity. To evaluate in vivo translation, we administered steady-state Ex-4 (3.5 pM/kg/min) or saline to control and mTBI mice over 7 days starting 48 h prior to or 1 h post-sham or mTBI (30 g weight drop under anesthesia). Ex-4 proved well-tolerated and fully ameliorated mTBI-induced deficits in novel object recognition 7 and 30 days post-trauma. Less mTBI-induced impairment was evident in Y-maze, elevated plus maze, and passive avoidance paradigms, but when impairment was apparent Ex-4 induced amelioration. Together, these results suggest that Ex-4 may act as a neurotrophic/neuroprotective drug to minimize mTBI impairment.

  6. Different distribution of neuromedin S and its mRNA in the rat brain: NMS peptide is present not only in the hypothalamus as the mRNA, but also in the brainstem.

    Science.gov (United States)

    Mori, Miwa; Mori, Kenji; Ida, Takanori; Sato, Takahiro; Kojima, Masayasu; Miyazato, Mikiya; Kangawa, Kenji

    2012-01-01

    Neuromedin S (NMS) is a neuropeptide identified as another endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1, which have also been identified as types 1 and 2 receptors for neuromedin U structurally related to NMS. Although expression of NMS mRNA is found mainly in the brain, spleen, and testis, the distribution of its peptide has not yet been investigated. Using a newly prepared antiserum, we developed a highly sensitive radioimmunoassay for rat NMS. NMS peptide was clearly detected in the rat brain at a concentration of 68.3 ± 3.4 fmol/g wet weight, but it was hardly detected in the spleen and testis. A high content of NMS peptide was found in the hypothalamus, midbrain, and pons-medulla oblongata, whereas abundant expression of NMS mRNA was detected only in the hypothalamus. These differing distributions of the mRNA and peptide suggest that nerve fibers originating from hypothalamic NMS neurons project into the midbrain, pons, or medulla oblongata. In addition, abundant expression of type 2 receptor mRNA was detected not only in the hypothalamus, but also in the midbrain and pons-medulla oblongata. These results suggest novel, unknown physiological roles of NMS within the brainstem.

  7. Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats.

    Science.gov (United States)

    Darsalia, Vladimer; Mansouri, Shiva; Ortsäter, Henrik; Olverling, Anna; Nozadze, Nino; Kappe, Camilla; Iverfeldt, Kerstin; Tracy, Linda M; Grankvist, Nina; Sjöholm, Åke; Patrone, Cesare

    2012-05-01

    Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto–Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 μg/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2–4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-1R agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions.

  8. Usefulness of early diastolic mitral annular velocity to predict plasma levels of brain natriuretic peptide and transient heart failure development after device closure of atrial septal defect.

    Science.gov (United States)

    Masutani, Satoshi; Taketazu, Mio; Mihara, Chihiro; Mimura, Yuko; Ishido, Hirotaka; Matsunaga, Tamotsu; Kobayashi, Toshiki; Senzaki, Hideaki

    2009-12-15

    Device closure of atrial septal defect (ASD) is sometimes followed by elevation of plasma brain natriuretic peptide (BNP), a marker of heart failure, and progression to heart failure. This study tested the hypothesis that the underlying diastolic dysfunction, assessed on tissue Doppler images (TDI) before device closure, can predict BNP level after ASD closure. The study subjects were 39 consecutive patients (age 27.5 +/- 16.3 years, range 5 to 63) who underwent device closure for ASD. Echocardiographic evaluation using TDI and 2-dimensional and pulse wave Doppler were performed, together with plasma BNP measurement 1 day before and 2 days after ASD closure. Before ASD closure, an age-dependent decrease was noted in left ventricular relaxation, assessed by early diastolic mitral annular velocity. ASD closure resulted in a decrease in early diastolic mitral annular velocity (from 14.7 to 12.3 cm/s, p linear regression identified early diastolic mitral annular velocity before ASD closure and age as independent predictors of BNP levels after ASD closure (p annular velocity developed exertional dyspnea after the procedure. In conclusion, our results indicate that TDI measurements could be useful to detect underlying diastolic dysfunction that can potentially cause heart failure after ASD closure and emphasize the importance of ASD closure at a young age before impairment of left ventricular relaxation.

  9. Dynamics of electrocardiographic changes, brain-natriuretic peptide and cortisol levels in a patient with stress (takotsubo cardiomyopathy: A case report

    Directory of Open Access Journals (Sweden)

    Đurić Ivica

    2013-01-01

    Full Text Available Introduction. Takotsubo cardiomyopathy is a transient acute heart failure syndrome caused by stress that provokes left ventricular mid-apical akinesis and mimics acute coronary syndrome. Case report. A 66-year-old woman had chest pain and dispnoea a few hours before hospitalization. A sudden emotional stressful event preceded the symptoms. Electrocardiographic abnormalities - precordial ST elevation and modest increase of cardiac troponin mimiced acute myocardial infarction. However, echocardiographic examination showed apical ballooning with markedly diminished left ventricle ejection fraction and the obstruction in the outflow tract of the left ventricle. Coronary angiography at admission showed no coronary stenosis and slower blood flow through the left anterior descending artery. According to anamnesis, echocardiography and coronarography finding we established the diagnosis of stress cardiomyopathy - takotsubo cardiomyopathy. We described in details the slow but dynamic electrocardiographic changes, levels of brain natriuretic peptide, cortisol and echocardiography evolution of disease during a 4-month follow-up till the full recovery. Conclusion. Stress (takotsubo cardiomyopathy - became an important differential diagnosis of acute anterior myocardial infarction and it should be reconsidered every time when emotionally stressed patients with transient-apical akinesis or dyskinesis of the LV are present.

  10. NEW POSSIBILITIES FOR EVALUATION OF SEVERITY AND PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE BASED ON N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE PLASMA LEVEL

    Directory of Open Access Journals (Sweden)

    A. S. Galjavich

    2016-01-01

    Full Text Available Aim. To study an importance of plasma N-terminal pro-brain natriuretic peptide (N-proBNP in evaluation of severity and prognosis in patients with chronic heart failure (CHF of ischemic genesis.Material and methods. 77 patients (60 men and 17 women; 59,4±10,7 y.o. with CHF of ischemic genesis were included in the study. All patients had sinus rhythm and history of Q wave myocardial infarction. Standard examination was performed to all patients. Besides N-proBNP plasma level and patients yearly survival were evaluated.Results. N-proBNP plasma level had direct correlation with clinical indices (exercise tolerance, blood pressure, heart rate and echocardiographic heart sizes. N-proBNP plasma level had relationship with prognosis of CHF patients. Baseline N-proBNP level was more than 2 times higher in died patients in comparison with survived patients. The yearly survival rate of CHF patients was 51,3% if N-proBNP level had been more than 400 fmol/ml (>15% of normal value. The clinico-laboratory index (based on N-proBNP plasma level of severity and prognosis in CHF patients was developed.Conclusion. The clinico-laboratory index based on N-proBNP plasma level is easy to use and can improve medical practice.

  11. NEW POSSIBILITIES FOR EVALUATION OF SEVERITY AND PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE BASED ON N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE PLASMA LEVEL

    Directory of Open Access Journals (Sweden)

    A. S. Galjavich

    2009-01-01

    Full Text Available Aim. To study an importance of plasma N-terminal pro-brain natriuretic peptide (N-proBNP in evaluation of severity and prognosis in patients with chronic heart failure (CHF of ischemic genesis.Material and methods. 77 patients (60 men and 17 women; 59,4±10,7 y.o. with CHF of ischemic genesis were included in the study. All patients had sinus rhythm and history of Q wave myocardial infarction. Standard examination was performed to all patients. Besides N-proBNP plasma level and patients yearly survival were evaluated.Results. N-proBNP plasma level had direct correlation with clinical indices (exercise tolerance, blood pressure, heart rate and echocardiographic heart sizes. N-proBNP plasma level had relationship with prognosis of CHF patients. Baseline N-proBNP level was more than 2 times higher in died patients in comparison with survived patients. The yearly survival rate of CHF patients was 51,3% if N-proBNP level had been more than 400 fmol/ml (>15% of normal value. The clinico-laboratory index (based on N-proBNP plasma level of severity and prognosis in CHF patients was developed.Conclusion. The clinico-laboratory index based on N-proBNP plasma level is easy to use and can improve medical practice.

  12. N-terminal pro-brain natriuretic peptide can be an adjunctive diagnostic marker of hyper-acute phase of Kawasaki disease.

    Science.gov (United States)

    Kwon, Hyuksool; Lee, Jin Hee; Jung, Jae Yun; Kwak, Young Ho; Kim, Do Kyun; Jung, Jin Hee; Chang, Ikwan; Kim, Kyuseok

    2016-12-01

    The purpose of this study was to determine whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level could be a useful marker for Kawasaki disease in the pediatric emergency department (PED) and in the presence of fever duration of 4 days or less (hyper-acute phase of Kawasaki disease). Medical records of patients who were 1 month to 15 years old of age and presented at the PED with suspected Kawasaki disease from January 1, 2010, to December 31, 2014, were collected retrospectively. Two hundred thirty-nine patients with a history of fever for 4 days or less were diagnosed with Kawasaki disease, as well as 111 patients with other febrile diseases, and were enrolled. The NT-proBNP level was significantly higher in patients with Kawasaki disease (Kawasaki disease vs. other febrile disease group, 444.8 (189.7-951.5) vs. 153.4 (68.9-287.6) pg/mL; p Kawasaki disease was 0.763 (95 % CI 0.712-0.814).

  13. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations

    Science.gov (United States)

    Chen, Virginia; Hollander, Zsuzsanna; Leipsic, Jonathon A.; Hague, Cameron J.; DeMarco, Mari L.; FitzGerald, J. Mark; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.

    2017-01-01

    There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80). These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD. PMID:28328968

  14. Relationship between the brain natriuretic peptide (BNP) level and remission of diabetic nephropathy with microalbuminuria: a 3-year follow-up study.

    Science.gov (United States)

    Seki, N; Matsumoto, T; Fukazawa, M

    2015-02-01

    The aim of the study was to examine the relationship between the brain natriuretic peptide (BNP) level and progression or remission of diabetic nephropathy with microalbuminuria for 3 years. The subjects were 100 Japanese type 2 diabetes mellitus outpatients with microalbuminuria. Associations between metabolic parameters at baseline [HbA1c, systolic blood pressure (SBP), urine albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and BNP] and the progression or remission of diabetic nephropathy were examined for 3 years. A total of 83 patients were examined at the end of the 3-year period, including 17 with remission to normoalbuminuria, 47 with continuing microalbuminuria, and 19 with progression to macroalbuminuria. HbA1c, ACR, and BNP differed significantly among the 3 groups (p=0.024, premission of diabetic nephropathy (p=0.029, p=0.012, respectively). ROC curve analysis gave a cutoff value for BNP of 14.9 pg/ml for prediction of remission of diabetic nephropathy (p=0.016). The BNP level has a relationship with diabetic nephropathy and a low BNP level predicts remission of diabetic nephropathy. Therefore, monitoring of BNP can play an important role in management of diabetic nephropathy.

  15. Peptides and Food Intake

    OpenAIRE

    Carmen Sobrino Crespo; Aranzazu Perianes Cachero; Lilian Puebla Jiménez; Vicente eBarrios; Eduardo eArilla

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the r...

  16. Satiety signalling histaminergic system and brain-gut peptides in regulation of food intake in rats with portocaval anastomosis.

    Science.gov (United States)

    Fogel, W A; Stasiak, A; Lewinski, A; Maksymowicz, M; Jochem, J

    2008-08-01

    Brain histamine plays a regulatory role in feeding behaviour, acting as an inhibitory modulator. Portocaval anastomosis (PCA) is associated with cerebral aminergic systems alterations, including high histamine accumulation and release from neurons. Despite that, the rats with PCA eat significantly more, their body mass being lower than sham-operated animals. To disclose underlying regulatory mechanisms, food intake was measured before and after treatment with antagonists of histamine H(1) and H(2), orexin type 1 (OX(1)) and cannabinoid type 1 (CB(1)) receptors in adult male Lewis rats 6 months following the end-to-side PCA or sham operation. Hypothalamic concentrations of orexin A and histamine as well as serum concentrations of leptin, insulin and cholecystokinin (CCK) were analysed. PCA rats with body mass lower by 30%, have consumed more feed and water 150% and 200%, respectively. The modifying effects of pyrilamine, ranitidine, SB 334867 and rimonabant were less pronounced in PCA compared with sham-operated rats. Hypothalamic orexin A and histamine concentrations were higher in PCA rats than in the control group with intact portocaval system. In PCA rats, serum concentrations of CCK were higher, leptin concentrations lower, while there were no differences between the groups in insulin levels. In conclusion, the adaptive mechanisms efficiently render PCA rats less sensitive to peripheral and central anorexigenic signals. Orexin A appears to be involved in the counteracting mechanisms preventing further body mass loss in PCA rats.

  17. N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    José Tuñón

    Full Text Available Several papers have reported elevated plasma levels of natriuretic peptides in patients with a previous diagnosis of cancer. We have explored whether N-terminal pro-brain natriuretic peptide (NT-proBNP plasma levels predict a future diagnosis of cancer in patients with coronary artery disease (CAD.We studied 699 patients with CAD free of cancer. At baseline, NT-proBNP, galectin-3, monocyte chemoattractant protein-1, soluble tumor necrosis factor-like weak inducer of apoptosis, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin I plasma levels were assessed. The primary outcome was new cancer diagnosis. The secondary outcome was cancer diagnosis, heart failure requiring hospitalization, or death.After 2.15±0.98 years of follow-up, 24 patients developed cancer. They were older (68.5 [61.5, 75.8] vs 60.0 [52.0, 72.0] years; p=0.011, had higher NT-proBNP (302.0 [134.8, 919.8] vs 165.5 [87.4, 407.5] pg/ml; p=0.040 and high-sensitivity C-reactive protein (3.27 [1.33, 5.94] vs 1.92 [0.83, 4.00] mg/L; p=0.030, and lower triglyceride (92.5 [70.5, 132.8] vs 112.0 [82.0, 157.0] mg/dl; p=0.044 plasma levels than those without cancer. NT-proBNP (Hazard Ratio [HR]=1.030; 95% Confidence Interval [CI]=1.008-1.053; p=0.007 and triglyceride levels (HR=0.987; 95%CI=0.975-0.998; p=0.024 were independent predictors of a new cancer diagnosis (multivariate Cox regression analysis. When patients in whom the suspicion of cancer appeared in the first one-hundred days after blood extraction were excluded, NT-proBNP was the only predictor of cancer (HR=1.061; 95%CI=1.034-1.088; p<0.001. NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001 along with age, and use of insulin and acenocumarol.NT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings.

  18. Value of serum brain natriuretic peptide levels in the prognosis of brain damage after cardiopulmonary resuscitation%血清脑钠肽水平对心肺复苏后脑损伤的预测价值研究

    Institute of Scientific and Technical Information of China (English)

    李钦浩; 巩晓娜; 周娆娆; 刘朋; 张磊; 亓雪梅; 蒋芳杰

    2013-01-01

    OBJECTIVE To evaluate the effect of serum brain natriuretic peptide levels on brain damage at the early stage after cardiopulmonary resuscitation (CPR). METHODS There were 34 patients with restoration of spontaneous circulation after successful CPR.After 2 months of successful cardiopulmonary resuscitation (CPR) , patients with GCS score ≥ 12 were mild brain damage (I group, male 6 cases, female 8 cases); GCS score 9 ≤ GCS ≤ 11 were moderate brain damage (II group, male 4 cases, female 6 cases); GCS score 3 ≤ GCS ≤ 8 were severe brain damage (Ⅲ group, male 5 cases, and female 5 cases) . Control group was consisted of 15 healthy volunteers. All of the patients' venous blood were respectively collected and BNP was detected by enzyme linked immunosorbent assay at 2, 8, 12, 24 and 48 h after restoring of independent circulation. RESULTS Compared the age, sex, start time of cardiac arrest to recovery in cardiopulmonary resuscitation (CPR) group and control group, differences were not statistically significant (P> 0.05); at 2, 8, 12, 24 and 48 h, serum BNP levels in I , II and Ⅲ groups were significantly higher than the control group (P < 0.05); And in the trail group, I group was significantly lower than the II group (P< 0.05); II group and was significantly lower than the HI group (P< 0.05). CONCLUSION Serum BNP levels can reflect cardiopulmonary resuscitation (CPR) early after HPC ischemia brain damage, and for the assessment of the recovery cardiopulmonary resuscitation (CPR) has an important value.%目的 探讨血清脑钠肽(BNP)对心肺复苏后脑损伤的预测的价值.方法 34例经心肺复苏后自主循环恢复的患者,以心肺复苏成功后2个月格拉斯哥昏迷评分(GCS)≥12为轻度脑损伤(Ⅰ组),男6例,女8例;9≤GCS≤11为中度脑损伤(Ⅱ组),男4例,女6例;3≤GCS≤8为重度脑损伤(Ⅲ组),男5例,女5例.另外选取14例健康者(女8例,男6例)作为对照组.所有患者均在自主循环恢复后2、8

  19. Preparation, Component Analysis and Anti-Ageing Effect of Brain Active Peptide of Sucking Pig Brain%乳猪脑活性多肽的制备,成分分 析及实验动物抗脑老化研究

    Institute of Scientific and Technical Information of China (English)

    张文治; 苏心; 秦进喜; 张国福; 孔繁明; 吴剑涓; 只达石

    2001-01-01

    Objective: To study the preparation,component and anti-ageing effect of the brain active peptide of sucking pig brain. Methods: Through homogenate, degrease, heat, hydrolyze, centrifugation and ultrafiltration of sucking pig brain tissue, the brain active peptide was prepared. It was measured by physical and biochemical methods and its anti-ageing effect was co- mared compared with the expensive Cerebrolysin made in Austria. Results: The analysis of high pressure lipid chromato- graphy(HPLC) showed that both peak areas of the brain active peptide and Cerebrolysin were identical and some amino-acid contents of the brain active peptide were more than those of Cerebrolysin. Conclusion: The product of brain active peptide ac- cords with the PRC Hygiene Ministry standard about brain protein hydrolytic reagent injection 《WS-198(X-171)-97(1)》.%目的:制备乳猪脑活性多肽替代价格昂贵的进口脑活素,用于临床治疗。方法:乳猪脑组织经匀浆、脱 脂、加热、消化、离心、超滤,制备脑活性多肽,并与奥地利产脑活素对比进行理化检测,并用SAM-P/8早老鼠进行 脑活性多肽抗脑老化的研究。结果:高效液相色谱分析,乳猪脑活性多肽峰型分布与奥地利产脑活素基本一致。 氨基酸成分分析,一些氨基酸含量高于奥地利产脑活素。结论:制备的脑活性多肽注射液符合中华人民共和国卫 生部《WS198(X-171)-97(1)》有关脑蛋白水解物注射液部标准(试行)。

  20. 重组人脑钠肽治疗失代偿性充血性心力衰竭的研究进展%Research progress on the treatment of compensatory Congestive Heart Failure with recombinant human brain natriuretic peptide

    Institute of Scientific and Technical Information of China (English)

    张麦叶; 姬秋和

    2009-01-01

    重组人脑钠肽(rhBNP)为一种合成肽,作用与内源性脑钠肽相似,具有扩张血管、利尿、利钠、抗交感神经系统、降低醛固酮和内皮素等作用,具有降压不加快心率,不激活肾素.血管紧张素.醛固酮系统等特点.现已有许多临床实验证实其在治疗充血性心力衰竭(CHF)方面,具有有效改善心功能、减轻心脏负荷及心室重构等优势,目前rhBNP已经上市,并且已经在临床上应用于充血性心力衰竭的治疗.本文就rhBNP的药理作用,与CHF的关系,以及其治疗失代偿性CHF的进展作一综述.%Recombinant human brain natriuretic peptide(rhBNP) is a synthetic peptide, its role is similar to endogenous brain natriuretic peptide, with effects on expanding blood vessel, diuretic, natriuretic, anti-sympathetic nervous system, decreasing plasma aldoste-rone and endothelin, also with characteristic of depress urization while neither speeding up the heart rate, nor activating the renin-angiotensin-aldosterone system. A number of studies had confirmed that recombinant human brain natriuretic peptide was effective in the treatment of Congestive Heart Failure (CHF), it could effectively improve the cardiac function, reduce the cardiac load and reverse left ventricular remodeling. It is now put on to market and applied in clinical treatment of Congestive Heart Failure. The article introduces rh-BNP pharmacologic action, the relationship with CHF, and the research progress on the treatment of CHF.

  1. Relation between plasma brain natriuretic peptide, serum indexes of collagen type I turnover, and left ventricular remodeling after reperfused acute myocardial infarction.

    Science.gov (United States)

    Cerisano, Giampaolo; Pucci, Paolo Domenico; Sulla, Antonio; Tommasi, Mariasilvia; Raspanti, Silvia; Santoro, Giovanni Maria; Antoniucci, David

    2007-03-01

    The aim of the study is to investigate the relation between plasma brain natriuretic peptide (BNP), collagen type I turnover, and left ventricular (LV) remodeling after primary angioplasty. Echo-Doppler, BNP, carboxy-terminal telopeptide of procollagen type I (ICTP), C-terminal propeptide of procollagen type I (PICP), and their ratio PICP/ICTP (as an index of coupling between the synthesis and degradation of collagen type I) were evaluated at days 1 and 3 and months 1 and 6 after primary angioplasty in 56 consecutive patients with a first large acute myocardial infarction (AMI). During the 6 months after AMI, a direct relation was shown between BNP and ICTP (day 1, r = 0.54, p = 0.000; day 3, r = 0.64, p = 0.000; month 1, r = 0.64, p = 0.000; month 6, r = 0.41, p = 0.005) and BNP and PICP/ICTP (day 1, r = -0.54, p = 0.003; day 3, r = -0.58, p = 0.000; month 1, r = -0.50, p = 0.000; month 6, r = -0.30, p = 0.043), but not between BNP and PICP. Using analysis of covariance, relations between BNP and ICTP and PICP/ICTP were independent from infarct size. Patients with LV remodeling had significantly higher plasma ICTP and BNP levels and lower PICP/ICTP than patients without LV remodeling. Day-1 ICTP independently predicted 6-month remodeling (exp beta = 2.14, 95% confidence interval 1,120 to 3,550, p = 0.01). In conclusion, a relation exists between plasma BNP collagen type I turnover and LV remodeling after reperfused AMI.

  2. Association of Atrial Fibrillation and Amino-terminal Pro-brain Natriuretic Peptide Concentrations in Patients After Off-Pump Coronary Artery Bypass Grafting

    Institute of Scientific and Technical Information of China (English)

    Junquan Li; Qinghua Zhang; Weichen Tian; Hongyu Liu

    2008-01-01

    Objectives To investigate the possible role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the occurrence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG).Methods This study group included 70 consecutive patients scheduled for elective off-pump CABG.The patients with ejection fraction (EF) less than 0.30,history of AF,use of class Ⅰor Ⅲ antiarrhythmic drug,implanted pacemaker,postoperative myocardial infarction or chest reopening for pericardial tamponade were excluded.Preoperative and postoperative serum NT-proBNP levels were measured by radioimmunoassay technique.Results Postoperative AF occurred in 15 patients (21.4%);these patients had significantly higher median NT-proBNP levels when compared with those without AF after the operation (P<0.01).Using multivariate logistic regression analyses,an increase in NT-proBNP level after CABG was found to be independently associated with AF (OR=3.78,95% IC=1.81~4.89,P<0.01 ).Increased age,diabetes mellitus,preoperative use of β-blocker,proximal right coronary artery involvement,and longer operation time were also associated with AF.Conclusions These results indicated that AF was associated with higher NT-proBNP concentrations after off pump CABG;the increase in NT-proBNP after CABG may play an important role in the occurrence of AF after the operation.The further studies are needed to define the reason that lead to higher NT-proBNP concentrations among the patients who present AF after off pump CABG.

  3. Predictive value of N-terminal pro-brain natriuretic peptide in combination with the sequential organ failure assessment score in sepsis

    Institute of Scientific and Technical Information of China (English)

    JU Min-jie; ZHU Du-ming; TU Guo-wei; HE Yi-zhou; XUE Zhang-gang; LUO Zhe; WU Zhao-guang

    2012-01-01

    Background The prognostic power of n-terminal pro-brain natriuretic peptide (NT-proBNP) in sepsis is disputable and unstable among different models.We attempt to evaluate the prognostic potential of NT-proBNP in combination with the sequential organ failure assessment (SOFA) score in sepsis.Methods In this retrospective study,100 consecutive sepsis patients were enrolled.Clinical data such as admission SOFA,the Acute Physiologic and Chronic Health Evaluation score,shock prevalence,use of lung protective ventilation,vasopressors,and glucocorticoids were recorded.Additionally,serum creatinine (Scr1 and Scr3) and NT-proBNP (NT-proBNP1 and NT-proBNP3) were assayed and evaluated at admission and on day 3 respectively.Results △NT-proBNP (NT-proBNP3 minus NT-proBNP1) (P <0.001,Hazard ratio (HR)=1.245,95% confidence interval (C/),1.137-1.362) and admission SOFA (P <0.001,HR=1.197,95% C/,1.106-1.295) were independently related to in-hospital mortality.Their combination was a more robust predictor for in-hospital mortality than either of them individually.Patients with high △NT-proBNP and SOFA had the poorest prognosis.Conclusions In our study,both △NT-proBNP and SOFA were independent predictors of septic patients' prognosis.Moreover,the combination of △NT-proBNP and admission SOFA provided a novel strategy that contained information regarding both the response to treatment and sepsis severity.

  4. Influence of preoperative serum N-terminal pro-brain type natriuretic peptide on the postoperative outcome and survival rates of coronary artery bypass patients

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    Thomas Schachner

    2010-01-01

    Full Text Available BACKGROUND: The N-terminal fragment of pro-brain type natriuretic peptide (NT-proBNP is an established biomarker for cardiac failure. OBJECTIVE: To determine the influence of preoperative serum NT-proBNP on postoperative outcome and mid-term survival in patients undergoing coronary artery bypass grafting (CABG. METHODS: In 819 patients undergoing isolated CABG surgery preoperative serum NT-proBNP levels were measured. NT-proBNP was correlated with various postoperative outcome parameters and survival rate after a median follow-up time of 18 (0.5-44 months. Risk factors of mortality were identified using χ2, Mann-Whitney test, and Cox regression. RESULTS: NT-proBNP levels >430 ng/ml and >502 ng/ml predicted hospital and overall mortality (p502 ng/ml (p=0.001. Age, preoperative serum creatinine, diabetes, chronic obstructive pulmonary disease, low left ventricular ejection fraction and BNP levels >502 ng/ml were isolated as risk factors for overall mortality. Multivariate Cox regression analysis, including the known factors influencing NT-proBNP levels, identified NT-proBNP as an independent risk factor for mortality (OR = 3.079 (CI = 1.149-8.247, p = 0.025. Preoperative NT-proBNP levels >502 ng/ml were associated with increased ventilation time (p=0.005, longer intensive care unit stay (p=0.001, higher incidence of postoperative hemofiltration (p=0.001, use of intra-aortic balloon pump (p502 ng/ml predict mid-term mortality after isolated CABG and are associated with significantly higher hospital mortality and perioperative complications.

  5. Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, X.Q. [Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China); Hong, H.S. [Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Lin, X.H. [Department of Emergency Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Chen, L.L. [Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Li, Y.H. [Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China)

    2014-07-11

    The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

  6. N-terminal pro-brain natriuretic peptide and cardiovascular or all-cause mortality in the general population: A meta-analysis

    Science.gov (United States)

    Geng, Zhaohua; Huang, Lan; Song, Mingbao; Song, Yaoming

    2017-01-01

    The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the general population remains controversial. We conducted this meta-analysis to investigate the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population. PubMed and Embase databases were systematically searched from their inception to August 2016. Prospective observational studies that investigated the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population were eligible. A summary of the hazard ratio (HR) and 95% confidence interval (CI) of mortality were calculated by the highest versus the lowest category of NT-proBNP concentrations. Eleven studies with a total of 25,715 individuals were included. Compared individuals in the highest with those in the lowest category of NT-proBNP, the pooled HR was 2.44 (95% CI 2.11–2.83) for all-cause mortality, 3.77 (95% CI 2.85–5.00) for cardiovascular mortality, and 2.35 (95% CI 1.45–3.82) for coronary heart disease mortality, respectively. Subgroup analyses indicated that the effects of NT-proBNP on the risk of cardiovascular mortality (RR 2.27) and all-cause mortality (RR 3.00) appeared to be slightly lower among men. Elevated NT-proBNP concentrations appeared to be independently associated with increased risk of cardiovascular and all-cause mortality in the general population. PMID:28134294

  7. The Relationship between Serum Pro‐Brain Natriuretic Peptide (Pro‐BNP Levels and Pulmonary Arterial Hypertension (PAH in Patients with Limited Scleroderma

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    Seyedeh Zahra Mirfeizi

    2014-08-01

    Full Text Available Introduction: Pulmonary arterial hypertension (PAH is a late progressive sclerodermarelated complication, which can lead to right heart failure and cor pulmonale. Given that cardiac catheterization is a diagnostic method of choice for PAH, and considering the high risks of this method, the purpose of this study was to evaluate the relationship between serum Pro‐Brain natriuretic peptide (Pro‐BNP Levels and PAH in patients with limited scleroderma. Materials and Methods: In this cross sectional study , during June 2011‐ Dec 2013, referring patients to two major educational hospitals, Mashhad‐ Iran, with scleroderma, who were afflicted with the disease for at least two years (or more, were enrolled in the study if they met the inclusion and exclusion criteria. All the patients underwent echocardiography to determine the pulmonary artery pressure (PAP. Afterwards, the subjects were referred to a lung center for performing body plethysmography, carbon monoxide diffusing capacity (DLCO, and 6‐ minute walk test (6MWT. Pro‐BNP Serum level was determined using flourescent immune assay method. Results: The present study included 20 patients (18 female subjects with the mean age of 43.28±9.56 yrs, and the mean pro‐BNP level of 138 pg/ml. The logarithmic correlation between PAP values, Forced Vital Capacity /DLCO ratio, and pro‐BNP level, which was measured using Pearson's correlation coefficient, showed a significant association among these variables( respectively, r=0.76, P0.001; r=0.677, P=0.011. Moreover, the DLCO decrease was associated with increasing pro‐BNP level, though this relationship was not significant. Conclusion: This study showed that there was a significant relationship between the serum levels of pro‐BNP marker and increased PAP in the echocardiography, DLCO reduction, and FVC/DLCO increase. In fact, this serum marker can be used in patients with systemic scleroderma (SSc to evaluate the status of PAH.

  8. 重组人脑利钠肽在慢性肺源性心脏病失代偿期的疗效观察%Curative Effect Observation of Recombinant Human Brain Natriuretic Peptide in Decompensated Chronic Cor Pulmonale

    Institute of Scientific and Technical Information of China (English)

    李翊; 刘爱东; 陈小会

    2015-01-01

    目的 探讨重组人脑利钠肽在慢性肺源性心脏病失代偿期的治疗效果.方法 选择天津市第一医院内科病房的慢性肺源性心脏病失代偿期患者70例患者临床资料进行回顾性分析.结果 试验组总有效率优于对照组(P<0.05),14 d血清脑利钠肽、肺动脉压、左室射血分数均优于对照组(P<0.05).结论 重组人脑利钠肽能改善慢性肺源性心脏病失代偿期症状,临床治疗效果显著.%Objective Study therapeutic effect of recombinant human brain natriuretic peptide in decompensated chronic cor pulmonale. Methods Chronic pulmonary heart disease from in the Department of internal medicine of Tianjin First Hospital ward patients with decompensated 70 patients clinical data were retrospectively analyzed. Results The total effective rate of experimental group was significantly better than the control group,P < 0.05, 14 d of serum brain natriuretic peptide, pulmonary artery pressure, left ventricular ejection fraction was significantly better than the control group (P < 0.05). Conclusion Recombinant human brain natriuretic peptide can obviously improve the chronic cor pulmonale decompensation symptoms.

  9. Top-down identification of endogenous peptides up to 9 kDa in cerebrospinal fluid and brain tissue by nanoelectrospray quadrupole time-of-flight tandem mass spectrometry.

    Science.gov (United States)

    Möhring, Thomas; Kellmann, Markus; Jürgens, Michael; Schrader, Michael

    2005-02-01

    Recent work on protein and peptide biomarker patterns revealed the difficulties in identifying their molecular components, which is indispensable for validation of the biological context. Cerebrospinal fluid and brain tissue are used as sources to discover new biomarkers, e.g. for neurodegenerative diseases. Many of these biomarker candidates are peptides with a molecular mass of highly efficient mass spectrometric purification and identification tool after off-line decomplexation of biological samples by liquid chromatography. After initial peptidomic screening with matrix-assisted laser desorption/ionization (MALDI) TOFMS, the elution behaviour in chromatography and the exact molecular mass were used to locate the same signals in nanoelectrospray measurements. Most of the peaks detected in MALDI-TOFMS could be retrieved in nanoelectrospray quadrupole TOFMS. Suitable collision energies for informative fragment spectra were investigated for different parent ions, charge states and molecular masses. After collision-induced dissociation, the resulting fragmentation data of multiply charged ions can become much more complicated than those derived from tryptic peptide digests. However, the mass accuracy and resolution of quadrupole TOF instruments results in high-quality data suitable for determining peptide sequences. The protein precursor, proteolytic processing and post-translational modifications were identified by automated database searches. This is demonstrated by the exemplary identifications of thymosin beta-4 (5.0 kDa) and NPY (4.3 kDa) from rat hypothalamic tissue and ubiquitin (8.6 kDa) from human cerebrospinal fluid. The high data quality should also allow for de novo identification. This methodology is generally applicable for peptides up to a molecular mass of about 10 kDa from body fluids, tissues or other biological sources.

  10. Relationship between N-terminal pro-brain natriuretic peptide, obesity and the risk of heart failure in middle-aged German adults.

    Directory of Open Access Journals (Sweden)

    Janine Wirth

    Full Text Available Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status.A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years and heart failure cases outside the sub-cohort (n = 197. Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2.Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR and 95% confidence interval (CI: 2.56 (1.49-4.41 for the top versus bottom tertile of NT-proBNP, ptrend:<0.01. In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85-3.49, 2.72 (1.42-5.22, and for obese: 3.29 (1.04-10.40, reference, 3.74 (1.52-9.21.Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms.

  11. Does Serum N-Terminal pro-Brain Natriuretic Peptide Level Predict the Severity of Angiographic Lesions in Patients with Acute Coronary Syndrome?

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    Afsaneh Rajabiani

    2015-10-01

    Full Text Available Background: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP, a polypeptide secreted by ventricular myocytes in response to stretch, was suggested as a predictor of adverse prognosis of the acute coronary syndrome (ACS. We examined the association between NT-proBNP level and angiographic findings in ACS patients to determine whether it could be used as a predictor of the severity of angiographic lesions.Methods: This cross-sectional study was performed on 126 patients with chest pain or other ischemic heart symptoms suggestive  of ACS.  Venous  blood  samples  were  drawn  to  measure  serum  levels  of  NT-proBNP. Afterward,  coronary angiography was performed and the patients were categorized into four groups according to the number of coronary vessels with significant stenosis. The severity of angiographic lesions was assessed with the Gensini scoring system.Results: According to angiographic diagnosis, 11 (8.7% patients had normal coronary arteries (no coronary artery disease [CAD] and 115 (91.3% had CAD, of whom 108 (85.7% had obstructive CAD and 7 (5.6% had minimal CAD. The serum NT-proBNP concentration was higher in the CAD group than in the non-CAD group (p value <0.01. A progressive significant increase in the NT-proBNP concentration according to the Gensini score and the number of involved vessels was reported after adjustment for sex and age. Furthermore, the Receiver Operating Characteristic Curve (ROC analysis indicated that an NT-proBNP cut-point of 400 pg/ml could predict obstructive CAD with a sensitivity of 65% and a specificity of 78%.Conclusion: Higher levels of NT-proBNP among our ACS patients were associated with the severity of angiographic lesions in terms of both the Gensini score and the number of involved vessels. This finding underscores the potential role of NT-proBNP in predicting the severity of CAD before performing angiography.

  12. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults

    DEFF Research Database (Denmark)

    Kistorp, Caroline; Raymond, Ilan; Pedersen, Frants;

    2005-01-01

    B-type natriuretic peptides have been shown to predict cardiovascular disease in apparently healthy individuals but their predictive ability for mortality and future cardiovascular events compared with C-reactive protein (CRP) and urinary albumin/creatinine ratio is unknown.......B-type natriuretic peptides have been shown to predict cardiovascular disease in apparently healthy individuals but their predictive ability for mortality and future cardiovascular events compared with C-reactive protein (CRP) and urinary albumin/creatinine ratio is unknown....

  13. Liposome-siRNA-peptide complexes cross the blood-brain barrier and significantly decrease PrP on neuronal cells and PrP in infected cell cultures.

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    Bruce Pulford

    Full Text Available BACKGROUND: Recent advances toward an effective therapy for prion diseases employ RNA interference to suppress PrP(C expression and subsequent prion neuropathology, exploiting the phenomenon that disease severity and progression correlate with host PrP(C expression levels. However, delivery of lentivirus encoding PrP shRNA has demonstrated only modest efficacy in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a new siRNA delivery system incorporating a small peptide that binds siRNA and acetylcholine receptors (AchRs, acting as a molecular messenger for delivery to neurons, and cationic liposomes that protect siRNA-peptide complexes from serum degradation. CONCLUSIONS/SIGNIFICANCE: Liposome-siRNA-peptide complexes (LSPCs delivered PrP siRNA specifically to AchR-expressing cells, suppressed PrP(C expression and eliminated PrP(RES formation in vitro. LSPCs injected intravenously into mice resisted serum degradation and delivered PrP siRNA throughout the brain to AchR and PrP(C-expressing neurons. These data promote LSPCs as effective vehicles for delivery of PrP and other siRNAs specifically to neurons to treat prion and other neuropathological diseases.

  14. Identification of a novel brain derived neurotrophic factor (BDNF)-inhibitory factor: regulation of BDNF by teneurin C-terminal associated peptide (TCAP)-1 in immortalized embryonic mouse hypothalamic cells.

    Science.gov (United States)

    Ng, Tiffany; Chand, Dhan; Song, Lifang; Al Chawaf, Arij; Watson, John D; Boutros, Paul C; Belsham, Denise D; Lovejoy, David A

    2012-02-10

    The teneurins are a family of four large transmembrane proteins that are highly expressed in the central nervous system (CNS) where they have been implicated in development and CNS function. At the tip of the carboxyl terminus of each teneurin lies a 43-amino acid sequence, that when processed, could liberate an amidated 41-residue peptide. We have called this region the teneurin C-terminal associated peptide (TCAP). Picomolar concentrations of the synthetic version of TCAP-1 inhibit stress-induced cocaine reinstatement in rats. Because cocaine-seeking is associated with increased brain derived neurotrophic factor (BDNF) in the brain, we examined whether synthetic mouse TCAP-1 has the potential to regulate BDNF expression in immortalized mouse neurons. Immortalized mouse neurons (N38; mHypoE38) show strong FITC-labeled [K(8)]-TCAP-1 uptake and BDNF labeling in the cytosol. Moreover, FITC-labeled [K(8)]-TCAP-1 bound competitively to membrane fractions. In culture, the labeled TCAP-1 peptide could be detected on cell membranes within 15 min and subsequently became internalized in the cytosol and trafficked toward the nucleus. Administration of 10(-8)M unlabeled TCAP-1 to cultures of the N38 cells resulted in a significant decrease of total cell BDNF immunoreactivity over 4h as determined by western blot and ELISA analyses. Real-time PCR, utilizing primers to the various BDNF transcripts showed a significant decline of promoter IIB- and VI-driven transcripts. Taken together, these studies indicated that in vitro, TCAP-1 induces a significant decline in BDNF transcription and protein labeling in embyronic mouse immortalized hypothalamic neurons. Thus, TCAP-1 may act as a novel BDNF inhibitory factor.

  15. 狂犬病毒糖蛋白衍生物作为靶脑载体初探%New Brain Delivery Vector: Rabies Virus Glycoprotein-derived Peptide

    Institute of Scientific and Technical Information of China (English)

    王逸麟; 付爱玲

    2011-01-01

    血脑屏障( blood-brain barrier,BBB)阻碍了具有治疗潜力的大分子化合物从外周组织进入脑内.为了寻找一种高效、快速通过BBB的靶向性载体,实验通过罗丹明B标记的狂犬病毒糖蛋白衍生肽(RDP)注射入昆明小鼠体内,并于15 min、5h取大脑、脊髓及肝、肾等外周组织,冷冻切片观察其在体内的分布,并通过构建pET28 a-RDP-luciferase重组质粒,结果发现融合蛋白能快速地穿过血脑屏障分布于中枢神经系统,为治疗中枢神经系统的药物开发提供新的思路.%Blood-brain barrier (BBB) prevents the transport pathway of potential macromolecular protein from blood to brain in order to find an efficient brain delivery vector, the rhodamine B labeled rabies virus glycoprotein-derived peptide (RDP)is applied to inject Kunming mice, and 15 min or 5 h take the brain, spinal cord, liver, kidney and so on. Frozen sections were observed the distribution. The RDP gene and luciferase gene were fused to the pET28a plasmid. The fusion protein can cross the BBB and distributed in the central nervous system rapidly. RDP can be used in future engineering of therapeutic fusion proteins for BBB drug delivery.

  16. Incremental value of a combination of cardiac troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein for prediction of mortality in end-stage renal disease

    DEFF Research Database (Denmark)

    Hallén, Jonas; Madsen, Lene Helleskov; Ladefoged, Søren

    2011-01-01

    Abstract Objective. To determine the relative prognostic merits of C-reactive protein (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for prediction of all-cause death in patients with end-stage renal disease (ESRD) receiving haemodialysis. Material...... were predictive of death in univariate analysis. In multivariable analysis, elevated cTnT (> 0.01 µg/l) and CRP (> 1.0 mg/dl) remained significantly associated with mortality [hazard ratio (95% confidence interval), 3.2 (1.2-8.5), p = 0.017 for cTnT; 2.0 (1.0-3.8), p = 0.032 for CRP], while NT...

  17. Diagnostic value of troponin, myocardial enzymes, brain natriuretic peptide to acute myocardial infarction patients%肌钙蛋白、心肌酶谱联合脑钠肽与急性心梗相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈杰民

    2012-01-01

      目的研究肌钙蛋白(cTnI,cTnT)、心肌酶谱联合脑钠肽对急性心肌梗死(acute myocardial infarction,AMI)的诊断价值.方法住院的 AMI 患者104例,正常对照组来自我院体检科60例.研究两组之间的肌钙蛋白、心肌酶谱联合脑钠肽指标的应用价值.结果 AMI 组治疗前和对照组之间的心肌酶指标包括谷草转氨酶(AST)、肌酸激酶(CK)、肌酸激酶同工酶(CKMB)、乳酸脱氢酶(LDH),心梗指标包括肌红蛋白 Mb、cTnI、cTnT,以及新指标脑钠肽(brain natriuretic peptide,BNP)在两组之间的差异明显(P〈0.05).BNP、BNP /AST、BNP /CKMB、BNP /cTnT 以及 BNP /cTnI 的曲线下面积均大于0.90,对治疗前急性心梗的诊断价值较高.指标的诊断价值排序为:BNP /cTnT > BNP /cTnI > BNP /CKMB > BNP /AST > BNP.结论 BNP、BNP /AST、BNP /CKMB、BNP /cTnT 以及 BNP /cTnI 的对急性心梗的诊断价值较高.%  Objective: To study diagnostic value of the study troponin (cTnI, cTnT), myocardial enzymes, brain natriuretic peptide to acute myocardial infarction. Methods: 104 cases of hospitalized patients with AMI and 60 cases of normal control group from the hospital physical examination department.Research the application value of troponin, myocardial enzymes, brain natriuretic peptide between the two groups. Results: AMI group before treatment and control group were significant differences in aspartate aminotransferase, creatine kinase, creatine kinase MB, lactate dehydrogenase, myocardial infarction indicators include myoglobin Mb , cTnI, cTnT, as wel as new indicators of brain natriuretic peptide (P ﹤0.05). BNP, BNP /AST, BNP / CKMB, BNP / cTnT and BNP / cTnI area under the curve were greater than 0.90, the diagnosis is high before the treatment of acute myocardial infarction. The diagnostic value of sort of targets: BNP / cTnT﹥ BNP / cTnI﹥ BNP / CKMB﹥ BNP / AST﹥ BNP. Conclusion: BNP, BNP / AST, BNP / CKMB, BNP / cTnT and BNP / cTnI have high

  18. Protein interaction analysis of senataxin and the ALS4 L389S mutant yields insights into senataxin post-translational modification and uncovers mutant-specific binding with a brain cytoplasmic RNA-encoded peptide.

    Directory of Open Access Journals (Sweden)

    Craig L Bennett

    Full Text Available Senataxin is a large 303 kDa protein linked to neuron survival, as recessive mutations cause Ataxia with Oculomotor Apraxia type 2 (AOA2, and dominant mutations cause amyotrophic lateral sclerosis type 4 (ALS4. Senataxin contains an amino-terminal protein-interaction domain and a carboxy-terminal DNA/RNA helicase domain. In this study, we focused upon the common ALS4 mutation, L389S, by performing yeast two-hybrid screens of a human brain expression library with control senataxin or L389S senataxin as bait. Interacting clones identified from the two screens were collated, and redundant hits and false positives subtracted to yield a set of 13 protein interactors. Among these hits, we discovered a highly specific and reproducible interaction of L389S senataxin with a peptide encoded by the antisense sequence of a brain-specific non-coding RNA, known as BCYRN1. We further found that L389S senataxin interacts with other proteins containing regions of conserved homology with the BCYRN1 reverse complement-encoded peptide, suggesting that such aberrant protein interactions may contribute to L389S ALS4 disease pathogenesis. As the yeast two-hybrid screen also demonstrated senataxin self-association, we confirmed senataxin dimerization via its amino-terminal binding domain and determined that the L389S mutation does not abrogate senataxin self-association. Finally, based upon detection of interactions between senataxin and ubiquitin-SUMO pathway modification enzymes, we examined senataxin for the presence of ubiquitin and SUMO monomers, and observed this post-translational modification. Our senataxin protein interaction study reveals a number of features of senataxin biology that shed light on senataxin normal function and likely on senataxin molecular pathology in ALS4.

  19. Enhancing Anticancer Effect of Gefitinib across the Blood-Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80.

    Science.gov (United States)

    Lin, Kuan-Hung; Hong, Shu-Ting; Wang, Hsiang-Tsui; Lo, Yu-Li; Lin, Anya Maan-Yuh; Yang, James Chih-Hsin

    2016-11-29

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood-brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd.3 cells. Gefitinib was encapsulated in small unilamellar liposomes modified with glutathione (GSH) and Tween 80 (SUV-G+T; one ligand plus one surfactant) or RF (SUV-RF; one α-helical cell-penetrating peptide). GSH, Tween 80, and RF were tested by the sulforhodamine B (SRB) assay to find their non-cytotoxic concentrations on bEnd.3 cells. The enhancement on gefitinib across the BBB was evaluated by cytotoxicity assay on human lung adenocarcinoma PC9 cells under the bEnd.3 cells grown on the transwell inserts. Our findings showed that gefitinib incorporated in SUV-G+T or SUV-RF across the bEnd.3 cells significantly reduced the viability of PC9 cells more than that of free gefitinib. Furthermore, SUV-RF showed no cytotoxicity on bEnd.3 cells and did not affect the transendothelial electrical resistance (TEER) and transendothelial permeability of sodium fluorescein across the BBB model. Moreover, flow cytometry and confocal laser scanning microscopy were employed to evaluate the endocytosis pathways of SUV-RF. The results indicated that the uptake into bEnd.3 cells was mainly through adsorptive-mediated mechanism via electrostatic interaction and partially through clathrin-mediated endocytosis. In conclusion, cell penetrating peptide-conjugated SUV-RF shed light on improving drug transport across the BBB via modulating the transcytosis pathway(s).

  20. Peptide identification

    Science.gov (United States)

    Jarman, Kristin H [Richland, WA; Cannon, William R [Richland, WA; Jarman, Kenneth D [Richland, WA; Heredia-Langner, Alejandro [Richland, WA

    2011-07-12

    Peptides are identified from a list of candidates using collision-induced dissociation tandem mass spectrometry data. A probabilistic model for the occurrence of spectral peaks corresponding to frequently observed partial peptide fragment ions is applied. As part of the identification procedure, a probability score is produced that indicates the likelihood of any given candidate being the correct match. The statistical significance of the score is known without necessarily having reference to the actual identity of the peptide. In one form of the invention, a genetic algorithm is applied to candidate peptides using an objective function that takes into account the number of shifted peaks appearing in the candidate spectrum relative to the test spectrum.

  1. Ammonia inhibits the C-type natriuretic peptide-dependent cyclic GMP synthesis and calcium accumulation in a rat brain endothelial cell line.

    Science.gov (United States)

    Konopacka, Agnieszka; Zielińska, Magdalena; Albrecht, Jan

    2008-05-01

    Recently we reported a decrease of C-type natriuretic peptide (CNP)-dependent, natriuretic peptide receptor 2 (NPR2)-mediated cyclic GMP (cGMP) synthesis in a non-neuronal compartment of cerebral cortical slices of hyperammonemic rats [Zielińska, M., Fresko, I., Konopacka, A., Felipo, V., Albrecht, J., 2007. Hyperammonemia inhibits the natriuretic peptide receptor 2 (NPR2)-mediated cyclic GMP synthesis in the astrocytic compartment of rat cerebral cortex slices. Neurotoxicology 28, 1260-1263]. Here we accounted for the possible involvement of cerebral capillary endothelial cells in this response by measuring the effect of ammonia on the CNP-mediated cGMP formation and intracellular calcium ([Ca2+]i) accumulation in a rat cerebral endothelial cell line (RBE-4). We first established that stimulation of cGMP synthesis in RBE-4 cells was coupled to protein kinase G (PKG)-mediated Ca2+ influx from the medium which was inhibited by an L-type channel blocker nimodipine. Ammonia treatment (1h, 5mM NH4Cl) evoked a substantial decrease of CNP-stimulated cGMP synthesis which was related to a decreased binding of CNP to NPR2 receptors, and depressed the CNP-dependent [Ca2+]i accumulation in these cells. Ammonia also abolished the CNP-dependent Ca2+ accumulation in the absence of Na+. In cells incubated with ammonia in the absence of Ca2+ a slight CNP-dependent increase of [Ca2+]i was observed, most likely representing Ca2+ release from intracellular stores. Depression of CNP-dependent cGMP-mediated [Ca2+]i accumulation may contribute to cerebral vascular endothelial dysfunction associated with hyperammonemia or hepatic encephalopathy.

  2. The NCAM-derived P2 peptide facilitates recovery of cognitive and motor function and ameliorates neuropathology following traumatic brain injury

    DEFF Research Database (Denmark)

    Klementiev, B; Novikova, T; Korshunova, Irina

    2008-01-01

    in the second immunoglobulin (Ig)-like module of NCAM, represents the natural cis-binding site for the first NCAM Ig module. The P2 peptide targets NCAM, thereby inducing a number of intracellular signaling events leading to the stimulation of neurite outgrowth and promotion of neuronal survival in vitro...... significantly improved postlesion recovery of motor and cognitive function, reduced neuronal degeneration, protected cells against oxidative stress, and increased reactive astrogliosis and neuronal plasticity in the sublesional area. P2 appeared rapidly in blood and cerebrospinal fluid after subcutaneous...

  3. Long-term treatment of aged Long Evans rats with a dietary supplement containing neuroprotective peptides (N-PEP-12) to prevent brain aging: effects of three months daily treatment by oral gavage.

    Science.gov (United States)

    Hutter-Paier, B; Reininger-Gutmann, B; Wronski, R; Doppler, E; Moessler, H

    2015-01-01

    Aging is associated with morphological and functional changes in the brain, resulting in the deterioration of cognitive performance. Growth factors like BDNF are suggested to be involved in the regulation of age-related processes in the brain. A novel dietary supplement produced from purified nerve cell proteins, N-PEP-12, has shown to share properties with naturally occurring peptide growth factors by stimulating neurite outgrowth and beneficial effects on neuronal survival and protection against metabolic stress in cell cultures. The current study investigates the effects of long-term intake on age-dependent memory decline by assessing cognitive performance and synaptic density. All the experiments were performed in aged Long Evans rats randomly assigned to saline or N-PEP-12 once daily by gavage over a period of three months. Behavioral tests were performed in the Morris Water Maze after one, two and three months of treatment. Histological examinations were performed in the hippocampal formation and in the entorhinal cortex by measuring the synaptic density. This study shows that the oral intake of N-PEP-12 has beneficial effects on the cognitive performance of aged animals and that these effects go along with an increase in the synaptic density. Thus, N-PEP-12 may help maintain memory and learning performance during the aging process.

  4. An optimized method for measuring hypocretin-1 peptide in the mouse brain reveals differential circadian regulation of hypocretin-1 levels rostral and caudal to the hypothalamus

    DEFF Research Database (Denmark)

    Justinussen, Jessica; Holm, A; Kornum, B R

    2015-01-01

    as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas....

  5. Inhibition of PlexA1-mediated brain tumor growth and tumor-associated angiogenesis using a transmembrane domain targeting peptide

    Science.gov (United States)

    Jacob, Laurent; Goetz, Jacky; Vermot, Julien; Fernandez, Aurore; Baumlin, Nadège; Aci-Sèche, Samia; Orend, Gertraud; Roussel, Guy; Crémel, Gérard; Genest, Monique; Hubert, Pierre; Bagnard, Dominique

    2016-01-01

    The neuropilin-plexin receptor complex regulates tumor cell migration and proliferation and thus is an interesting therapeutic target. High expression of neuropilin-1 is indeed associated with a bad prognosis in glioma patients. Q-RTPCR and tissue-array analyses showed here that Plexin-A1 is highly expressed in glioblastoma and that the highest level of expression correlates with the worse survival of patients. We next identified a developmental and tumor-associated pro-angiogenic role of Plexin-A1. Hence, by using molecular simulations and a two-hybrid like assay in parallel with biochemical and cellular assays we developed a specific Plexin-A1 peptidic antagonist disrupting transmembrane domain-mediated oligomerization of the receptor and subsequent signaling and functional activity. We found that this peptide exhibits anti-tumor activity in vivo on different human glioblastoma models including glioma cancer stem cells. Thus, screening Plexin-A1 expression and targeting Plexin-A1 in glioblastoma patients exhibit diagnostic and therapeutic value. PMID:27506939

  6. The evolution of peptide hormones.

    Science.gov (United States)

    Niall, H D

    1982-01-01

    Despite limitations in our present knowledge it is already possible to discern the main features of peptide hormone evolution, since the same mechanisms (and indeed the same hormone molecules) function in many different ways. This underlying unity of organization has its basis in the tendency of biochemical networks, once established, to survive and diversify. The most surprising recent findings in endocrinology have been the discovery of vertebrate peptide hormones in multiple sites within the same organism, and the reports, persuasive but requiring confirmation, of vertebrate hormones in primitive unicellular organisms (20, 20a). Perhaps the major challenge for the future is to define the roles and interactions of the many peptide hormones identified in brain (18). The most primitive bacteria and the human brain, though an enormous evolutionary distance apart, may have more in common than we have recognized until now. As Axelrod & Hamilton have pointed out in a recent provocative article, "The Evolution of Cooperation" (1), bacteria, though lacking a brain, are capable of adaptive behavior that can be analysed in terms of game theory. It is clear that we can learn a great deal about the whole evolutionary process from a study of the versatile and durable peptide hormones molecules.

  7. Increased ventricular ectopic activity in relation to C-reactive protein, and NT-pro-brain natriuretic peptide in subjects with no apparent heart disease

    DEFF Research Database (Denmark)

    Sajadieh, A; Nielsen, OW; Rasmussen, Verner

    2006-01-01

    BACKGROUND: Subjects with frequent ventricular premature complexes (VPC) and no apparent heart disease make a heterogenic group with regard to prognosis. Some biomarkers have recently proved useful in risk stratification in different heart diseases. We examined prognostic impact of NT-Pro-brain...... with a significantly higher risk of death and acute myocardial infarction. These subjects deserve primary prevention measures and further work up for structural heart disease....

  8. Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers

    DEFF Research Database (Denmark)

    Guo, Song; Gøtze, Jens Peter; Jeppesen, Jørgen L;

    2015-01-01

    The natriuretic peptides (NPs), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), have vasoactive functions that concern humans and most animals, but their specific effects on cerebral circulation are poorly understood. We therefore examined t...

  9. The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

    Directory of Open Access Journals (Sweden)

    Kvido Smitka

    2013-01-01

    Full Text Available Eating disorders such as anorexia (AN and bulimia nervosa (BN are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY, peptide YY (PYY, cholecystokinin (CCK, leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE, serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.

  10. Peptides and the new endocrinology

    Science.gov (United States)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  11. A Novel Role for Brain Natriuretic Peptide: Inhibition of IL-1β Secretion via Downregulation of NF-kB/Erk 1/2 and NALP3/ASC/Caspase-1 Activation in Human THP-1 Monocyte

    Directory of Open Access Journals (Sweden)

    Letizia Mezzasoma

    2017-01-01

    Full Text Available Interleukin-1β (IL-1β is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1β processing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1β and its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents. IL-1β is a strong regulator of Brain Natriuretic Peptide (BNP, a hormone involved in cardiovascular homeostasis by guanylyl cyclase Natriuretic Peptide Receptor (NPR-1. An emerging role of BNP in inflammation and immunity, although proposed, remains largely unexplored. Here, we newly demonstrated that, in human THP-1 monocytes, LPS/ATP-induced IL-1β secretion is strongly inhibited by BNP/NPR-1/cGMP axis at all the molecular mechanisms that tightly control its production and release, NF-kB, ERK 1/2, and all the elements of NALP3/ASC/Caspase-1 inflammasome cascade, and that NALP3 inflammasome inhibition is directly related to BNP deregulatory effect on NF-kB/ERK 1/2 activation. Our findings reveal a novel potent anti-inflammatory and immunomodulatory role for BNP and open new alleys of investigation for a possible employment of this endogenous agent in the treatment of inflammatory/immune-related and IL-1β/NF-kB/ERK1/2/NALP3/ASC/Caspase-1-associated diseases.

  12. 生物标志物β淀粉样蛋白与颅脑创伤%The correlation of amyloid β peptide and traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    张赛

    2010-01-01

    @@ 随着我国现代化交通、建筑等生产行业的日益繁荣,颅脑创伤(traumatic brain injury,TBI)发生率居高不下,同时也已成为青少年致死致残的首要原因,考虑到TBI所引起的严重社会经济后果,预计在2020年TBI将位居全球疾病第三位[1].

  13. Effects of recombinant human brain natriuretic peptide on the prognosis of patients with acute anterior myocardial infarction undergoing primary percutaneous coronary intervention: a prospective, multi-center, randomized clinical trial

    Science.gov (United States)

    Hou, Ai-Jie; Zang, Hong-Yun; Huang, Ru-Gang; Zheng, Xiao-Qun; Lin, Hai-Long; Wang, Wei; Hou, Ping; Xia, Fei; Li, Zhan-Quan

    2017-01-01

    Background This study aims to investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on serum enzyme data, cardiac function parameters and cardiovascular events in patients with acute anterior myocardial infarction (MI). Methods A total of 421 patients with acute anterior or extensive anterior MI were collected from 20 hospitals. These patients were randomly divided into two groups: rhBNP and control groups. Both groups of patients received primary percutaneous coronary intervention (PCI) within the effective time window. In the rhBNP group, rhBNP administration (0.01 µg/kg/min, 48–72 successive hours) was performed as early as possible after hospital admission. Prior to and one or seven days after PCI, serum concentrations of cardiac troponin (cTnT), creatine kinase-MB (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. At seven days and 6 months after PCI, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd) and stroke volume (SV) were measured using 2D Doppler echocardiography. MACEs that occurred during hospitalization and within 6 months after PCI were recorded. Results At postoperative days one and seven, serum concentrations of cTnT were significantly lower in the rhBNP group than in the control group. At postoperative day one, serum concentrations of CK-MB were significantly lower in the rhBNP group than in the control group. At postoperative day seven, serum concentrations of NT-proBNP were significantly lower in the rhBNP group than in the control group, and LVEF was significantly greater in the rhBNP group than in the control group. At postoperative 6 months, LVEDd was significantly lower in the rhBNP group compared with the control group. In addition, SV and LVEF were significantly greater in the rhBNP group than in the control group. By postoperative month 6, the incidence of composite cardiovascular events (16.0% vs. 26.0%, P=0.012), cardiac death (7.0% vs.13

  14. Molecular assembly and biosynthesis of acetylcholinesterase in brain and muscle: The roles of t-peptide, FHB domain and N-linked glycosylation

    Directory of Open Access Journals (Sweden)

    Vicky P. Chen

    2011-10-01

    Full Text Available Acetylcholinesterase (AChE is responsible for the hydrolysis of the neurotransmitter, acetylcholine, in the nervous system. The functional localization and oligomerization of AChE T variant are depending primarily on the association of their anchoring partners, either collagen tail (ColQ or proline rich membrane anchor (PRiMA. Complexes with ColQ represent the asymmetric forms (A12 in muscle, while complexes with PRiMA represent tetrameric globular forms (G4 mainly found in brain and muscle. Apart from these traditional molecular forms, a ColQ-linked asymmetric form and a PRiMA-linked globular form of hybrid cholinesterases (ChEs, having both AChE and BChE catalytic subunits, were revealed in chicken brain and muscle. The similarity of various molecular forms of AChE and BChE raises interesting question regarding to their possible relationship in enzyme assembly and localization. The focus of this review is to provide current findings about the biosynthesis of different forms of ChEs together with their anchoring proteins.

  15. Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2013-11-01

    Full Text Available The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs, a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics.

  16. An investigation of appetite-related peptide transcript expression in Atlantic cod (Gadus morhua) brain following a Camelina sativa meal-supplemented feeding trial.

    Science.gov (United States)

    Tuziak, Sarah M; Rise, Matthew L; Volkoff, Hélène

    2014-10-25

    Camelina sativa is a hardy oilseed crop with seeds that contain high levels of ω3 polyunsaturated fatty acids and protein, which are critical components of fish feed. Camelina might thus be used as a cheaper and more sustainable supplement to fish-based products in aquaculture. Atlantic cod, Gadus morhua, is a species of interest in the aquaculture industry due to a decrease in wild populations and subsequent collapse of some cod fisheries. As cod are carnivorous fish, it is necessary to determine how this species physiologically tolerates plant-based diets. In this study, juvenile Atlantic cod were subjected to 13 weeks of either 15 or 30% camelina meal (CM)-supplemented diets or a control fish meal feed. Growth and food intake were evaluated and the mRNA expression of appetite-related hormones [pro-melanin-concentrating hormone (pmch), hypocretin (synonym: orexin, hcrt), neuropeptide Y (npy) and cocaine- and amphetamine-regulated transcript (cart)] was assessed using quantitative real-time PCR in brain regions related to food intake regulation (telencephalon/preoptic area, optic tectum/thalamus and hypothalamus). CM inclusion diets caused decreases in both growth and food intake in Atlantic cod. Optic tectum pmch transcript expression was significantly higher in fish fed the 30% CM diet compared to fish fed the 15% CM diet. In the hypothalamus, compared to fish fed the control diet, hcrt expression was significantly higher in fish fed the 30% CM diet, while npy transcript expression was significantly higher in fish fed the 15% CM diet. cart mRNA expression was not affected by diet in any brain region. Further studies are needed to determine which factors (e.g. anti-nutritional factors, palatability and nutritional deficits) contribute to reduced feed intake and growth, as well as the maximum CM inclusion level that does not negatively influence feed intake, growth rate and the transcript expression of appetite-related factors in Atlantic cod.

  17. Serum Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated with Low Left Ventricular Ejection Fraction and Elevated Plasma Brain-Type Natriuretic Peptide Level

    Science.gov (United States)

    Fujita, Shu-ichi; Tanaka, Suguru; Maeda, Daichi; Morita, Hideaki; Fujisaka, Tomohiro; Takeda, Yoshihiro; Ito, Takahide; Ishizaka, Nobukazu

    2017-01-01

    Background Recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR), a biomarker of subclinical levels of inflammation, is significantly correlated with cardiovascular events. Purpose We investigated the association between suPAR and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and plasma B-type natriuretic peptide (BNP) among cardiac inpatients. Methods and Results In total, 242 patients (mean age 71.3 ± 9.8 years; 70 women) admitted to the cardiology department were enrolled in the study. suPAR was significantly correlated with LVEF (R = -0.24, P 3236 pg/mL) was associated with low LVEF ( 300 pg/mL) with an odds ratio of 3.84 (95% confidence interval [CI], 1.22–12.1) and 5.36 (95% CI, 1.32–21.8), respectively, after adjusting for age, sex, log-transformed estimated glomerular filtration rate (log(eGFR)), C-reactive protein, and diuretic use. The association between suPAR and LVMI was not statistically significant. In multivariate receiver operating characteristic analysis, addition of log(suPAR) to the combination of age, sex, log(eGFR) and CRP incrementally improved the prediction of low LVEF (area under the curve [AUC], 0.827 to 0.852, P = 0.046) and BNP ≥ 300 pg/mL (AUC, 0.869 to 0.906; P = 0.029). Conclusions suPAR was associated with low LVEF and elevated BNP, but not with left ventricular hypertrophy, independent of CRP, renal function, and diuretic use among cardiac inpatients who were not undergoing chronic hemodialysis. PMID:28135310

  18. Elevated plasma levels of N-terminal pro-brain natriuretic peptide in patients with chronic hepatitis C during interferon-based antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    J(o)rg Bojunga; Christoph Sarrazin; Georg Hess; Stefan Zeuzem

    2006-01-01

    AIM: To investigate plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP), an established marker of cardiac function, in patients with chronic hepatitis C during interferon-based antiviral therapy.METHODS: Using a sandwich immunoassay, plasma levels of NT-proBNP were determined in 48 patients with chronic hepatitis C at baseline, wk 24 and 48 during antiviral therapy and at wk 72 during follow-up.RESULTS: Plasma NT-proBNP concentrations were significantly increased (P < 0.05) at wk 24, 48 and 72 compared to the baseline values. NT-proBNP concentrations at baseline and wk 24 were closely correlated (r = 0.8; P < 0.001). At wk 24, 7 (14.6%)patients had NT-proBNP concentrations above 200 ng/L compared to 1 (2%) patient at baseline (P = 0.059).Six of these 7 patients had been treated with high-dose IFN-α induction therapy. In multiple regression analysis,NT-proBNP was not related to other clinical parameters,biochemical parameters of liver disease or virus load and response to therapy.CONCLUSION: Elevated levels of NT-proBNP during and after interferon-based antiviral therapy of chronic hepatitis C may indicate the presence of cardiac dysfunction, which may contribute to the clinical symptoms observed in patients during therapy. Plasma levels of NT-proBNP may be used as a diagnostic tool and for guiding therapy in patients during interferonbased antiviral therapy.

  19. Relationship of brain natriuretic peptide concentrations to left ventricular function and adverse outcomes in children with end-stage renal disease undergoing hemodialysis.

    Science.gov (United States)

    Ouali, Sana; Bougmiza, Iheb; Abroug, Saoussen; Omezzine, Asma; Ben Salem, Helmi; Neffeti, Elyes; Remedi, Fahmi; Bouslema, Ali; Harabi, Abdelaziz; Boughzela, Essia

    2011-06-01

    B-type natriuretic peptide (BNP) is a biomarker of cardiovascular disease that is common in adults with chronic kidney disease (CKD). However, in children with CKD, the range and predictive power of BNP concentrations are not known. We aimed to determine the effect of HD on BNP, as well as the prognostic impact of BNP, in end-stage renal disease (ESRD) children undergoing hemodialysis (HD). Thirty-five children with chronic renal failure (16 boys age 12.1 ± 3.7 years) on maintenance HD were included. BNP level was measured, and Doppler echocardiography was performed 30 min before (pre-HD BNP) and 30 min after (post-HD BNP) HD in each patient. An adverse event was defined as all-cause death and heart failure hospitalization. The median pre-HD BNP, the post-HD BNP, and the change in BNP were, respectively, 240 pg/ml (72 to 3346), 318 pg/ml (79 to 3788), and 9 pg/ml (-442 to 1889). Pre-HD BNP concentration was negatively correlated with left ventricular (LV) ejection fraction (r = -0.41, P = 0.018). During a mean follow-up of 39 ± 14 months, 6 patients died, and 3 were hospitalized for heart failure. Using univariate analysis, BNP before and after HD as well as Doppler tissue imaging velocities had a strong graded relationship with adverse events. Cox proportional hazards model demonstrated that pre-HD body weight (P = 0.008), pre-HD BNP (P = 0.011), and post-HD BNP (P = 0.038) remained independent predictors of adverse outcome. Even in case of ESRD, BNP still strongly correlated with LV systolic and diastolic dysfunction and was associated with mortality in HD children.

  20. Dopamine-dependent behavioural stimulation by non-peptide delta opioids BW373U86 and SNC 80: 2. Place-preference and brain microdialysis studies in rats.

    Science.gov (United States)

    Longoni, R; Cadoni, C; Mulas, A; Di Chiara, G; Spina, L

    1998-02-01

    The motivational properties of the non-peptide delta-opioid receptor agonists BW373U86 and SNC 80 were investigated using the place-conditioning paradigm. BW373U86 (0.5-1.0 mg/kg s.c.) and SNC 80 (1.25-5.0 mg/kg s.c.) elicited significant preference for the drug-paired compartment, in a dose-related fashion. Naltrindole (5.0 mg/kg s.c.) pretreatment, while failing to modify preference when given alone, completely prevented place-preference induced by BW373U86 (1.0 mg/kg s.c.) and SNC 80 (1.25 mg/kg s.c.). The dopamine D1 receptor antagonist SCH23390, given at doses that do not affect place-preference (0.012 mg/kg s.c.), completely prevented the place-preference induced by BW373U86 and SNC 80. At the doses effective in eliciting place-preference, BW373U86 and SNC 80 failed to modify extracellular dopamine in the medial nucleus accumbens, while in the dorso-lateral caudate-putamen BW373U86 (1.0 and 2.5 mg/kg s.c.) reduced extracellular dopamine, and this effect was prevented by naltrindole (5.0 mg/kg s.c.). SNC 80, only at the dose of 5 mg/kg s.c., significantly reduced extracellular DA in the dorso-lateral caudate-putamen. The results indicate that stimulation of delta-opioid receptors has incentive properties that might be related to an indirect amplification of post-synaptic dopamine transmission.

  1. 脑钠肽在儿童心血管疾病诊治中的研究进展%Research advance of brain natriuretic peptide in the diagnosis and treatment of pediatric cardiovascular disease

    Institute of Scientific and Technical Information of China (English)

    吴利伟(综述); 王凤鸣(审校)

    2013-01-01

      脑钠肽(BNP)是一种主要来源于心室的心脏内分泌激素,具有很强的利钠、利尿、扩张血管、抑制肾素–血管紧张素–醛固酮系统(RAAS)和交感神经系统活性作用。研究表明,心血管疾病患儿的血浆BNP及氨基末端脑钠肽原(NT-proBNP)水平升高,可以反映心室功能变化。该文就BNP/NT-proBNP的生物学特性、检测方法、正常值范围及其在儿童心血管疾病诊治中的研究进展作一综述。%Brain natriuretic peptide(BNP) is a cardiac hormone mainly secreted by myocytes in the ventricular wall. It has strong action of natriuresis, diuresis, vasodilation, inhibition of renin-angiotensin-aldosterone system and sympathetic nervous system. The increased levels of BNP and NT-proBNP have been reported in children’s cardiovascular diseases in numerous stu-dies and can reflect cardiac function. This article simply reviews the BNP and NT-proBNP about its biology character, detection method, medical reference range and its progress in pediatric cardiovascular disease.

  2. Predictability of brain natriuretic peptide on the prognosis in elderly patients with septic shock%BNP水平对老年感染性休克患者预后评估的作用

    Institute of Scientific and Technical Information of China (English)

    崔志新; 卓裕丰; 陈伟杰; 李泽伦

    2014-01-01

    Objective:To investigate the predictability of brain natriuretic peptide ( BNP ) on the prognosis in elderly patients with septic shock. Methods:Seventy-eight elderly patients with septic shock recruited between June 2007 and October 2013 in the Intensive Care Unit, Panyu Hexian Memorial Hospital, were retrospectively analyzed. Patients were,according to their BNP levels at 6 and 24 h after admission,allocated to group A ( BNP0.05) . Compared with groups A and B,all indices were significantly heightened in group C ( all P0.05),与A组、B组比较,C组上述指标均显著升高( P<0.05)。结论:BNP水平对老年感染性休克患者预后的判断有一定意义,BNP水平≥500 pg/mL可能是患者病情加重及死亡率增高的一个重要判断指标。

  3. 血清脑钠肽水平与慢性阻塞性肺疾病的相关性研究%Correlation research between serum brain natriuretic peptide level and chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    钟晓华

    2015-01-01

    ObjectiveTo investigate and research correlation between serum brain natriuretic peptide (BNP) level and chronic obstructive pulmonary disease (COPD).MethodsThere were 80 COPD patients. BNP levels in acute exacerbation and clinical remission were observed and compared.ResultsThere were statistically significant differences of BNP levels in different COPD degree patients at the same period (P0.05). Grade Ⅲ and Ⅳ COPD in acute exacerbation had much higher BNP level than clinical remission, and the difference had statistical significance (P0.05),Ⅲ、Ⅳ级COPD患者急性加重期的BNP水平显著高于临床缓解期,差异具有统计学意义(P<0.05)。结论COPD患者疾病进展程度和BNP水平有着显著相关,病情越重则BNP水平变化越明显,可作为COPD的诊断和病情严重程度的判别依据。

  4. The clinical importance and change of brain natriuretic peptide in diagnosing chronic obstructive pulmonary disease%慢性阻塞性肺疾病中脑钠肽水平的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    王煜

    2013-01-01

    Objective: To investigate the changes of the levels of plasma brain natriuretic peptide (BNP) in patients with chronic obstructive pulmonary disease (COPD) and chronic cor pulmonale (CCP). Methods: Plasma BNP levels were detected in 30 patients with CCP at acute stage, compared with simple COPD group, and the rela tionship between it and PO2 , pulmonary artery pressure (PAP) was analyzed. Measurements were repeated in the same 30 patients with CCP at remission tage after therapy in hospital. Results: The levels of BNP at acute stage (262. 84 ± 47. 59)pg/ml and remission stage (128. 52 ±24. 82) pg/ml for CCP group were both higher than that in the simple COPD group (64.76 ± 12.03) pg/ml (P0. 05). In the acute stage of CCP group, BNP levels in the plasma were positively correlated with the PAP(r=0. 763, P0.05).结论:在COPD伴CCP患者中,血浆BNP水平上升,可能与缺氧、肺动脉高压(PAH)等因素相关.

  5. Peptide arrays for screening cancer specific peptides.

    Science.gov (United States)

    Ahmed, Sahar; Mathews, Anu Stella; Byeon, Nara; Lavasanifar, Afsaneh; Kaur, Kamaljit

    2010-09-15

    In this paper, we describe a novel method to screen peptides for specific recognition by cancer cells. Seventy peptides were synthesized on a cellulose membrane in an array format, and a direct method to study the peptide-whole cell interaction was developed. The relative binding affinity of the cells for different peptides with respect to a lead 12-mer p160 peptide, identified by phage display, was evaluated using the CyQUANT fluorescence of the bound cells. Screening allowed identification of at least five new peptides that displayed higher affinity (up to 3-fold) for MDA-MB-435 and MCF-7 human cancer cells compared to the p160 peptide. These peptides showed very little binding to the control (noncancerous) human umbilical vein endothelial cells (HUVECs). Three of these peptides were synthesized separately and labeled with fluorescein isothiocyanate (FITC) to study their uptake and interaction with the cancer and control cells using confocal laser scanning microscopy and flow cytometry. The results confirmed the high and specific affinity of an 11-mer peptide 11 (RGDPAYQGRFL) and a 10-mer peptide 18 (WXEAAYQRFL) for the cancer cells versus HUVECs. Peptide 11 binds different receptors on target cancer cells as its sequence contains multiple recognition motifs, whereas peptide 18 binds mainly to the putative p160 receptor. The peptide array-whole cell binding assay reported here is a complementary method to phage display for further screening and optimization of cancer targeting peptides for cancer therapy and diagnosis.

  6. Peptides and Food Intake

    Science.gov (United States)

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  7. Association between high-sensitivity cardiac troponin T and N-terminal pro-brain natriuretic peptide in a community based population

    Institute of Scientific and Technical Information of China (English)

    Xu Ruyi; Ye Ping; Luo Leiming; Sheng Li; Wu Hongmei; Xiao Wenkai; Zheng Jin

    2014-01-01

    Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury.However,it remains unclear whether subclinical myocardial injury is associated with NT-proBNP elevation in a community based population.Methods In a community based study,levels of hs-cTnT and of NT-proBNP were determined in 1 497 participants older than 45 years.The lower detection limit of the hs-cTnT assay used in the present study was 0.003 ng/ml.The association of hs-cTnT levels and NT-proBNP levels was analyzed.Results When the subjects with undetectable (<0.003 ng/ml),intermediate (0.003-0.014 ng/ml),and elevated (≥0.014 ng/ml) levels of hs-cTnT were compared (r=0.175,P <0.001),a strong association between the hs-cTnT levels and NT-proBNP levels was observed (β=-0.206,P <0.001; β=-0.118,P <0.001,respectively).In multivariable analyses,older age and hs-cTnT were positively and independently associated with NT-proBNP levels (β=0.341,P <0.001; β=0.143,P <0.001,respectively),and male gender and the levels of eGFR were inversely and independently associated with NT-proBNP levels.When the subjects with normal or elevated NT-proBNP were analyzed separately,the hs-cTnT level was not an independent predictor for the NT-proBNP level in the normal NT-proBNP group,whereas the hs-cTnT level was the only independent predictor for NT-proBNP level in the elevated NT-proBNP group (β=0.399,P <0.01).Conclusions In this community based population,NT-proBNP elevation was common.In addition to female gender and older age,subclinical myocardial injury indicated by the hs-cTnT level was another important factor in NT-proBNP elevation.

  8. BDNF pro-peptide regulates dendritic spines via caspase-3

    OpenAIRE

    Guo, J.; Ji, Y.; Y. Ding; Jiang, W.; Sun, Y.; B. Lu; Nagappan, G

    2016-01-01

    The precursor of brain-derived neurotrophic factor (BDNF) (proBDNF) is enzymatically cleaved, by either intracellular (furin/PC1) or extracellular proteases (tPA/plasmin/MMP), to generate mature BDNF (mBDNF) and its pro-peptide (BDNF pro-peptide). Little is known about the function of BDNF pro-peptide. We have developed an antibody that specifically detects cleaved BDNF pro-peptide, but not proBDNF or mBDNF. Neuronal depolarization elicited a marked increase in extracellular BDNF pro-peptide,...

  9. Modulation of gastric motility by brain-gut peptides using a novel non-invasive miniaturized pressure transducer method in anesthetized rodents.

    Science.gov (United States)

    Gourcerol, Guillaume; Adelson, David W; Million, Mulugeta; Wang, Lixin; Taché, Yvette

    2011-04-01

    Acute in vivo measurements are often the initial, most practicable approach used to investigate the effects of novel compounds or genetic manipulations on the regulation of gastric motility. Such acute methods typically involve either surgical implantation of devices or require intragastric perfusion of solutions, which can substantially alter gastric activity and may require extended periods of time to allow stabilization or recovery of the preparation. We validated a simple, non-invasive novel method to measure acutely gastric contractility, using a solid-state catheter pressure transducer inserted orally into the gastric corpus, in fasted, anesthetized rats or mice. The area under the curve of the phasic component (pAUC) of intragastric pressure (IGP) was obtained from continuous manometric recordings of basal activity and in responses to central or peripheral activation of cholinergic pathways, or to abdominal surgery. In rats, intravenous ghrelin or intracisternal injection of the thyrotropin-releasing hormone agonist, RX-77368, significantly increased pAUC while coeliotomy and cacal palpation induced a rapid onset inhibition of phasic activity lasting for the 1-h recording period. In mice, RX-77368 injected into the lateral brain ventricle induced high-amplitude contractions, and carbachol injected intraperitoneally increased pAUC significantly, while coeliotomy and cecal palpation inhibited baseline contractile activity. In wild-type mice, cold exposure (15 min) increased gastric phasic activity and tone, while there was no gastric response in corticotropin releasing factor (CRF)-overexpressing mice, a model of chronic stress. Thus, the novel solid-state manometric approach provides a simple, reliable means for acute pharmacological studies of gastric motility effects in rodents. Using this method we established in mice that the gastric motility response to central vagal activation is impaired under chronic expression of CRF.

  10. Relationship Between Prohormone Brain Natriuretic Peptide (NT-proBNP Level and Severity of Pulmonary Dysfunction in Patients With Chronic Congestive Heart Failure

    Directory of Open Access Journals (Sweden)

    Nazemiyeh Masoud

    2015-03-01

    Full Text Available Introduction: Congestive heart failure (CHF is a common disease and its prevalence is increasingin industrialized countries. NT-proBNP measurement is an established diagnostic test fordiagnosis of CHF in patients who present to emergency room with acute dyspnea. The primaryobject of this study was to determine the relationship between levels of brain natriuretic peptideprecursor and severity of lung function impairment in patients with chronic CHF.Methods: This cross-sectional and analytical study that performed in Tuberculosis andLung Disease Research Center of Tabriz University of Medical Sciences on 95 patients withchronic heart failure, and relation between NT-proBNP levels and pulmonary functionparameters were examined.Results: Sixty-four patients were male and 31 were female. The average age of male and femaleswas 62.90 ± 11.54 and 61.61 ± 11.98 years, respectively. A significant inverse linear correlationwas found between NT-proBNP and FEV1 (P<0.001, r = -0.367, FVC (P<0.001, r = -0.444,TLC (P=0.022, r = -0.238, maximal midexpiratory flow (MMEF (P=0.047, r = -0.207 andleft ventricular ejection fraction (LVEF (P<0.001, r = -0.461. A significant positive linearcorrelation was found between NT-proBNP and FEV1/FVC (P =0.013, r = 0.257, RV/TLC (P =0.003, r=0.303 and 5 Hz Raw (r = 0.231, P = 0.024.Conclusion: This study showed that, both restrictive and obstructive ventilator impairments canoccur in chronic CHF and as NT-proBNP increases appropriate to hemodynamic deterioration,pulmonary dysfunction increases.

  11. 肌钙蛋白I与N端脑钠肽原在慢性心衰危险预测中的应用价值分析%Value of troponin I and N-terminal pro-brain natriuretic peptide in predicting the risk of chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    朱湘慧; 钱银芬

    2016-01-01

    Objective To investigate the va1ue of troponin I and N- termina1 pro-brain natriuretic peptide in predicting the risk of chronic heart fai1ure. Methods A tota1 of 37 patients with chronic heart fai1ure who were treated in our hospita1 from September 2013 to September 2105 were enro11ed as observation group. Another 37 patients with norma1 cardiac function who were admitted to our hospita1 were enro11ed as contro1 group. Troponin I and N- termina1 pro-brain natriuretic peptide 1eve1s were determined for both groups after admission and compared between the two groups. Results Compared with the contro1 group, the observation group had significant1y higher mean 1eve1s of troponin I (4.5±3.0ng/m1) and N- termina1 pro-brain natriuretic peptide (769.5±322.5pg/m1) (P<0.05). The patients with cardiac function c1ass II had the 1owest 1eve1s of troponin I and N-termina1 pro- brain natriuretic peptide, and those with cardiac function c1ass IV had the highest 1eve1s of troponin I and N-termina1 pro- brain natriuretic peptide. The 1eve1s of troponin I and N-termina1 pro-brain natriuretic peptide showed significant differences across the three groups (P<0.05). Conclusion Troponin I and N- termina1 pro- brain natriuretic peptide can be measured to predict the condition of patients with chronic heart fai1ure and suggest the severity of their condition.%目的:对肌钙蛋白I与N端脑钠肽原在慢性心衰患者危险预测中的应用价值进行分析讨论。方法选择我院2013年9月-2015年9月间37例慢性心衰患者,将其作为观察组,同时随机选取心功能正常入院患者37例,将其作为对照组,所有患者入院后都进行肌钙蛋白I与N端脑钠肽原检测,比较两组患者肌钙蛋白I与N端脑钠肽原水平。结果观察组患者肌钙蛋白I水平平均为(4.5±3.0)ng/m1,明显高于对照组,患者N端脑钠肽原水平平均为(769.5±322.5)pg/m1,同样高于对照组,两组比较存在明显差异,P<0.05

  12. Bibliometric Analysis of Literatures on Research Focuses on Brain Natriuretic Peptide in Recent 4 Years%脑钠肽近4年研究热点文献计量学分析

    Institute of Scientific and Technical Information of China (English)

    王占胜; 胡健; 宋占春; 孟庐松

    2012-01-01

    Objective To present the hot topics on brain natriuretic peptide( BNP )research by analyzing the related literatures. Methods The research papers published from 2007 to June 2011 on this topic were analyzed by the method of citation analysis and the highly-cited references were clustered by SPSS software. Based on the contents of the papers in each cluster,the research focuses were concluded. Results The important research literatures about BNP were mainly published in well-known journal of cardiovascular disease and the comprehensive journals were in the second place. There were 5014 related papers covered in science citation index( SCI), of which 43 were cited more than 100 times. 7 clusters were formed according to their co-cited frequencies. Conclusion The research focuses are classified as: BNP and heart failure; BNP and coronary artery disease; BNP in comparison with atrial natriuretic peptide( ANP)in heart failure; BNP and creatinine clearance rate; BNP structure and basic function; BNP and right heart dysfunction caused by pulmonary hypertension; natriuretic peptide and the echocardiographic assessment of ventricular remodeling after myocardial infarction.%目的 调查有关脑钠肽(BNP)研究的文献,分析当前该主题的研究热点.方法 采用引文分析方法对2007 ~2011年6月有关该主题的重要文献进行调查分析,并用SPSS软件对高频被引文献进行聚类分析,根据各个类中的文献内容分析当前研究的热点.结果 有关BNP研究的重要文献多数发表于著名的心血管病专业刊物上,发表于著名综合刊物的次之.检得科学引文索引数据库(SCI)相关文献5014篇,其参考文献出现频次高于100次论文43篇.高被引论文聚类分析树图分7类.结论 BNP与心力衰竭、BNP与冠状动脉性疾病、BNP与心房利钠肽在心力衰竭中作用比较、BNP与肌酐清除率关系、BNP结构功能基础研究、BNP与肺动脉高压右心功能障碍及钠肽类与心肌

  13. A Clinical Study of Recombinant Human Brain Natriuretic Peptide on Patients with Acute Decompensated Heart Failure%重组人脑利钠肽治疗急性心力衰竭的疗效观察

    Institute of Scientific and Technical Information of China (English)

    周秀金; 卢竟前

    2013-01-01

    Objective:To observe the clinic efficacy and safety of used recombinant human brain natriuretie peptide (rh-BNP)on patients with acute decompensated heart failure.Methods:48 patients who suffered from acute decompensated heart failure patients were divided into rh-BNP group(n=22)and control group(n=26).The rh-BNP group received rh-BNP made by China and traditional heart failure treatment; the control group was treated with traditional heart failure treatment.The changes of the clinical efficacy, left ventricular ejection fraction (LVEF)and brain natriuretie peptide test parameters were observed. Results:After 7 days treatment, clinical efficacy improvements were more significant in rh-BNP group compared control group (81.7% vs 61.6,P<0.05).LVEF were improved in rh-BNP group compared with control group((51±6)%vs(46±5)%,P<0.01).and BNP level were decreased obviously in rh-BNP group than control group((498±209)pg/ml vs(642±318)pg/ml,P<0.01),and there had positive relation in BNP decrease and LVEF increased(P<0.05).Conclusion:The use of rh-BNP is efficient and safe for acute decompensated heart failure patient.And BNP test can provide a dog marker for diagnosis and prognostic.%目的:探讨在监测血清脑钠肽水平下,短期使用注射用重组人脑利钠肽治疗急性心力衰竭或慢性心力衰竭急性发作的临床效果。方法:48例急性心力衰竭患者根据是否使用注射用重组人脑利钠肽分为常规组和注射用重组人脑利钠肽组,对比两组治疗的临床效果和超声心动图情况,并监测BNP水平。结果:治疗7 d后,注射用重组人脑利钠肽组临床有效率明显好于常规组(81.7%vs61.6%,P<0.05),左室射血分数明显高于常规组(51±6)%vs(46±5)%,(P<0.01),且血清脑钠肽水平明显降低(498±209)pg/mL vs(642±318)pg/mL,(P<0.01),血清脑钠肽下降水平和左室射血分数提高水平差异有统计学意义(P<0.05),有

  14. Progress in use of brain natriuretic peptide in congenital heart disease and perioperative pediatric cardiac operation%脑钠肽在小儿先天性心脏病及围手术期的应用进展

    Institute of Scientific and Technical Information of China (English)

    肖书娜

    2013-01-01

    脑钠肽是一种神经内分泌激素,它与先天性心脏病患儿心功能不全和肺动脉高压程度呈正相关,已成为评估先天性心脏病患儿心功能不全程度、反映先天性心脏病患儿术前术后心功能状态的简便、准确的生物化学指标.它对先天性心脏病心脏手术预后有预测作用,对围手术期治疗有指导意义,能减少术后并发症和病死率,成为迅速、即时床边检查的辅助手段.该文就其与先天性心脏病的相关性和在先天性心脏病围手术期应用进展作一概述.%Brain natriuretic peptide (BNP) is a neuroendocrine hormone,which has a positive correlation with degree of cardiac dysfunction and pulmonary arterial hypertension of children with congenital heart disease (CHD).BNP has been shown to be a simple,accurate and useful biochemical indicator in assessing cardiac dysfunction degree and reflecting perioperative cardiac function state of children with CHD.It has prognostic value in congenital heart surgery and can guide the perioperative treatment and reduce the postoperative complications and mortality.It is a quick,instant bedside inspection supplementary means.This article describes the relevance between BNP and CHD and the application progress of BNP in pefioperative of CHD.

  15. Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep.

    Science.gov (United States)

    Smith, Jeremy T; Coolen, Lique M; Kriegsfeld, Lance J; Sari, Ika P; Jaafarzadehshirazi, Mohammad R; Maltby, Matthew; Bateman, Katherine; Goodman, Robert L; Tilbrook, Alan J; Ubuka, Takayoshi; Bentley, George E; Clarke, Iain J; Lehman, Michael N

    2008-11-01

    Reproductive activity in sheep is seasonal, being activated by short-day photoperiods and inhibited by long days. During the nonbreeding season, GnRH secretion is reduced by both steroid-independent and steroid-dependent (increased response to estradiol negative feedback) effects of photoperiod. Kisspeptin (also known as metastin) and gonadotropin-inhibitory hormone (GnIH, or RFRP) are two RFamide neuropeptides that appear critical in the regulation of the reproductive neuroendocrine axis. We hypothesized that expression of kisspeptin and/or RFRP underlies the seasonal change in GnRH secretion. We examined kisspeptin and RFRP (protein and mRNA) expression in the brains of ovariectomized (OVX) ewes treated with estradiol (OVX+E) during the nonbreeding and breeding seasons. In OVX+E ewes, greater expression of kisspeptin and Kiss1 mRNA in the arcuate nucleus and lesser expression of RFRP (protein) in the dorsomedial nucleus of the hypothalamus were concurrent with the breeding season. There was also a greater number of kisspeptin terminal contacts onto GnRH neurons and less RFRP-GnRH contacts during the breeding season (compared with the nonbreeding season) in OVX+E ewes. Comparison of OVX and OVX+E ewes in the breeding and nonbreeding season revealed a greater effect of steroid replacement on inhibition of kisspeptin protein and Kiss1 mRNA expression during the nonbreeding season. Overall, we propose that the two RFamide peptides, kisspeptin and RFRP, act in concert, with opposing effects, to regulate the activity of GnRH neurons across the seasons, leading to the annual change in fertility and the cyclical seasonal transition from nonbreeding to breeding season.

  16. Clinical Application of Plasma Brain Natriuretic Peptide in Acute Coronary Syndromes%血浆脑钠肽在急性冠状动脉综合征中的临床应用进展

    Institute of Scientific and Technical Information of China (English)

    陈作强

    2011-01-01

    脑钠肽是主要由心室肌细胞分泌的一种心脏神经激素,是心功能不全时机体的代偿机制之一.近年来研究表明,心肌缺血同样能够引起脑钠肽水平的升高,血浆脑钠肽与急性冠脉综合征的关系已经引起人们的关注.脑钠肽与NYHA分级和左室射血分数间存在较好的相关性,可作为预测急性冠脉综合征心室重塑、冠脉病变程度的有效指标,是急性冠脉综合征的独立预后因子,并作为高敏C反应蛋白、肌酸激酶同工酶和肌钙蛋白I等生化指标的有益补充,为急性冠脉综合征提供有价值的辅助诊断.%Brain natriuretic peptide ( BNP) is a cardiac neural hormone, secreted by cardiac myocytes, and one of the body's compensatory mechanisms during heart failure. Recent studies have shown that myocardial ischemia can cause elevated BNP levels. BNP may be an effective indicator to predict ventricular remodeling and the extent of coronary artery disease in acute coronary syndrome patients. It is also an independent predictors of acute coronary syndromes, and a useful addition to biochemical index such as hs-CRP, CK-MB and cTnl. This article reviews BNP's role in ACS and how it may be used as a diagnostic tool.

  17. Correlation between arterial wall stiffness, N-terminal prohormone of brain natriuretic peptide, functional and structural myocardial abnormalities in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy

    Directory of Open Access Journals (Sweden)

    Viktoriya Aleksandrovna Serhiyenko

    2013-12-01

    Full Text Available Aim. To assess arterial wall stiffness, plasma levels of of N-terminal prohormone of brain natriuretic peptide (NT-proBNP, as well as functional state and structure of the myocardium in patients with type 2 diabetes mellitus (T2DM and cardiac autonomic neuropathy (CAN.Materials and Methods. The study involved a total of 65 patients with T2DM. 12 had no evidence of cardiovascular disease (CVD or CAN, 14 were diagnosed with subclinical stage of CAN, 18 – with functional stage, and 21 – with organic stage. We measured aortic pulse wave velocity (PWV, aortic augmentation index (AIx, brachial artery AIx, ambulatory arterial stiffness index (AASI and plasma levels of NT-proBNP. Clinical examination included ECG, Holter monitoring, ambulatory BP measurement and echocardiography.Results. Patients with isolated T2DM showed a trend for increased vascular wall stiffness. PWV was increased in patients with subclinical stage of CAN. Aortic and brachial AIx, PWV and AASI were elevated in patients with functional stage of CAN, PWV being significantly higher vs. subclinical CAN subgroup. Organic stage was characterized by pathologically increased values of all primary parameters; PWV and AASI were significantly higher compared with other groups. Development and progression of CAN was accompanied by an increase in NT-proBNP plasma levels. Concentration of NT-proBNP was in direct correlation with left ventricular mass (LVM and PWV. PWV and LVM values also directly correlated between themselves.Conclusion. Development and progression of CAN in patients with T2DM is accompanied by an increase in vascular wall stiffness. The elevation of plasma NT-proBNP in patients with T2DM correlates with the development of CAN and is significantly and independently associated with an increase in LVM and PWV. Our data suggests the pathophysiological interconnection between metabolic, functional and structural myocardial abnormalities in patients with T2DM and CAN.

  18. Changes of plasma brain natriuretic peptide and amino-terminal pro-brain natriuretic peptide in children of congenital heart disease complicated with different degrees of pulmonary hypertension%先天性心脏病伴不同程度肺动脉高压患儿血浆脑钠肽及氨基末端脑钠肽前体的变化

    Institute of Scientific and Technical Information of China (English)

    郭俊晓; 张玉龙; 刘志平; 赵龙

    2015-01-01

    Objective To explore the changes of plasma brain natriuretic peptide (BNP) and aminoterminal pro-brain natriuretic peptide (NT-proBNP) in children with congenital heart disease (CHD) complicated with different degrees of pulmonary arterial hypertension (PAH).Methods Totally 60 children of left-right shunt congenital heart disease from December 2012 to December 2013 were enrolled.The pulnonary arterial systolic pressure was measured by echocardiography;the BNP and NT-proBNP level were measured and compared among patients with different degree of PAH.Results The plasma BNP and NT-proBNP were increased in non PAH, mild PAH, moderate PAH and severe PAH patients [(30 ± 26), (134 ± 22), (307 ± 86), (661 ± 67) ng/L;(94 ±35), (153 ± 25), (487 ± 213), (2 430 ± 1 278) ng/L].There were significant differences regarding plasma BNP among non PAH, mild PAH, moderate PAH and severe PAH patients (all P < 0.05);NT-proBNP showed statistical differences in severe PAH patients compared with that in non-PAH patients (P < 0.05) and no differences were observed among other patients (all P > 0.05).Conclusion In left to right shunt congenital heart disease children complicated with PAH, the plasma BNP and NT-proBNP levels increased with increasing of PAH degree, and can be used as an index to evaluate the degrees of PAH.%目的 分析先天性心脏病伴不同程度肺动脉高压(PAH)患儿血浆脑钠肽(BNP)及氨基末端脑钠肽前体(NT-proBNP)水平的变化情况.方法 纳入2012年12月至2013年12月内蒙古医科大学附属医院经超声心动图确诊的左向右分流先天性心脏病患儿60例.采用超声心动图评估肺动脉收缩压,比较不同程度PAH患儿血浆BNP及NT-proBNP水平差异.结果 无PAH患儿16例、轻度PAH患儿16例、中度PAH患儿14例、重度PAH患儿14例.血浆BNP及NT-proBNP水平在无PAH、轻度PAH、中度PAH和重度PAH患儿中依次升高[BNP: (30 ±26)、(134 ±22)、(307±86)、(661±67) ng/L;NT-proBNP:(94

  19. 测定脑胶质瘤患者神经肽、神经降压素的含量变化及意义%Clinical Significance and Detection of Neuro- Peptide and Neurotensin in Patients with Brain Glioma

    Institute of Scientific and Technical Information of China (English)

    尹秋霞; 司永兵; 齐法莲

    2001-01-01

    Objective To investigate the change of neuropeptide Y(NPY)and neurotensin(NT)in pqtients with brain glioma.Method The concentration of NPY and NT in and around brain glioma tissue and plasma were detected with inequilibrant radio- imunology method.Result NPY concentrqtion in brain glioma tissue was obviously higher than that in tissue around the tumor(P<0.01).The Concentration of NT in brain glioma tissue was obviously higher that in tissue around the glioma(P<0.01).Conclusion Detection of NPY and NTin brain glion aprovides basis for further study on brain glioma and explainning dlinical and imaginal symiptom of brain glioma.

  20. Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2011-01-01

    The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting that preecla......The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...

  1. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen;

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2...

  2. RFamide peptides in early vertebrate development

    Directory of Open Access Journals (Sweden)

    Guro Katrine Sandvik

    2014-12-01

    Full Text Available RFamides (RFa are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play.

  3. Effect of Recombinant Human Brain Natriuretic Peptide on Prognosis of Patients with Acute Severe Heart Failure%重组人脑利钠肽对急性重症心力衰竭患者预后影响

    Institute of Scientific and Technical Information of China (English)

    李晚泉; 方长庚; 曾小茹; 涂军荣; 郑晓东; 梁建光

    2015-01-01

    目的:探讨重组人脑利钠肽(rhBNP)对急性重症心力衰竭患者预后的影响。方法:将2010年8月至2013年8月收治的急性重症心力衰竭患者237例随机分为观察组(n=120)和对照组(n=117),对照组给予异舒吉治疗,观察组给予 rhBNP 治疗,比较两组气促缓解时间、住院时间及治疗前后尿量、液体入量、左室射血分数(LVEF)、每搏输出量(SV)、心脏指数(CI)、左心室舒张末期内径(LVDd)、N 末端 B 型利钠肽原(NT-proBNP)的变化。结果:治疗后,观察组24 h 尿量、LVEF明显高于对照组(P<0.05);观察组呼吸困难缓解时间、住院时间、NT-proBNP 水平、不良心血管事件发生率均明显低于对照组(P<0.05)。结论:rhBNP能有效改善急性重症心力衰竭患者左心室功能,缩短气促缓解时间、住院时间,降低不良心血管事件发生率。%Objective:To explore the effect of recombinant human brain natriuretic peptide (rhBNP)on the prognosis of patients with acute severe heart failure. Methods:237 patients with acute severe heart failure were randomly divided into observation group (n=120) and control group (n=117) treated by rhBNP and isosorbide dinitrate respectively from Aug 2010 to Aug 2013.The dyspnea remission time , hospitalization time and amount of urine before and after the treatment, the intake of liquid, left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac index (CI), left ventricular end diastolic diameter (LVDd), N terminal B type natriuretic peptide (NT-proBNP) changes were compared between the two groups. Results: Compared with the control group after the treatment, 24h urine volume and LVEF were significantly higher in the observation group (both P < 0.05), and the dyspnea remission time , hospitalization time , NT-proBNP levels , adverse cardiovascular event rates were significantly lower in the observation group (all P < 0

  4. Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons

    Institute of Scientific and Technical Information of China (English)

    Rui Yan; Tianwen Huang; Zhiqin Xie; Guannan Xia; Hui Qian; Xiaolin Zhao; Leping Cheng

    2013-01-01

    Serotonin (5-HT) neurons synthesize a variety of peptides.How these peptides are controlled during development remains unclear.It has been reported that the co-localization of peptides and 5-HT varies by species.In contrast to the situations in the rostral 5-HT neurons of human and rat brains,several peptides do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain.In this study,we found that the peptide substance P and peptide genes,including those encoding peptides thyrotropin-releasing hormone,enkephalin,and calcitonin gene-related peptide,were expressed in the caudal 5-HT neurons of mouse brain; these findings are in line with observations in rat and monkey 5-HT neurons.We also revealed that these peptides/peptide genes partially overlapped with the transcription factor Lmx1b that specifies the 5-HT cell fate.Furthermore,we found that the peptide cholecystokinin was expressed in developing dopaminergic neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell fate.By examining the phenotype of Lmx1b deletion mice,we found that Lmx1b was required for the expression of above peptides expressed in 5-HT or dopaminergic neurons.Together,our results indicate that Lmx1b,a key transcription factor for the specification of 5-HT and dopaminergic transmitter phenotypes during embryogenesis,determines some peptide phenotypes in these neurons as well.

  5. Hyponatremia and brain injury: absence of alterations of serum brain natriuretic peptide and vasopressin Hiponatremia e traumatismo cranioencefálico: ausência de alteração sanguínea do peptídeo natriurético cerebral e hormônio antidiurético

    Directory of Open Access Journals (Sweden)

    Karina Nascimento Costa

    2009-12-01

    Full Text Available OBJECTIVE: To study any possible relation between hyponatremia following brain injury and the presence of cerebral salt-wasting syndrome (CSWS or the syndrome of inappropriate secretion of antidiuretic hormone (SIADH, and if vasopressin, brain natriuretic peptide (BNP and aldosterone have a role in its mechanism. METHOD: Patients with brain injury admitted to the intensive care unit were included and had their BNP, aldosterone and vasopressin levels dosed on day 7. RESULTS: Twenty six adult patients were included in the study. Nine (34.6% had hyponatremia and presented with a negative water balance and higher values of urinary sodium, serum potassium and diuresis than patients with normonatremia. The serum levels of BNP, aldosterone, and vasopressin were normal and no relation was observed between plasma sodium and BNP, aldosterone or vasopressin. CONCLUSION: The most likely cause of hyponatremia was CSWS and there was no correlation between BNP, aldosterone and vasopressin with serum sodium level.OBJETIVO: Estudar a possível relação entre a hiponatremia seguindo traumatismo cranioencefálico e a presença da síndrome cerebral perdedora de sal (SCPS ou a síndrome da secreção inapropriada do hormônio antidiurético (SSIHAD, e se a vasopressina, peptídeo natriurético cerebral (BNP e aldosterona têm um papel nesse mecanismo. MÉTODO: Foram incluídos pacientes com traumatismo cranioencefálico admitidos na unidade de terapia intensiva e foram dosados no sétimo dia seguindo o trauma, BNP, aldosterona e vasopressina. RESULTADOS: Vinte e seis pacientes foram incluídos no estudo. Nove (34,6% tiveram hiponatremia e apresentaram um balanço hídrico mais negativo e altos valores de sódio urinário, potássio sérico e diurese quando comparados com o grupo que apresentou normonatremia. Os níveis séricos de BNP, aldosterona e vasopressina foram normais e não foi observada relação entre o sódio sérico e BNP, aldosterona e vasopressina

  6. 重组人脑利钠肽在应激性心肌病并急性泵衰竭中的应用%Application of recombinant human brain natriuretic peptide in stress cardiomyopathy complicated acute left heart failure

    Institute of Scientific and Technical Information of China (English)

    余浩; 胡晓军; 李姣; 孙玉真

    2016-01-01

    Objective:To observe therapeutic effect of lyophilized recombinant human brain natriuretic peptide (Lrh-BNP)on stress cardiomyopathy (SCM)complicated acute bump failure.Methods:A total of 23 patients with SCM complicated acute bump failure were randomly divided into routine treatment group (n=10,received routine treatment)and Lrh-BNP group (n=13,received Lrh-BNP based on routine treatment).Clinical symptoms and signs,cardiac function :left ventricular ejection fraction (LVEF),stroke volume (SV),cardiac index (CI),peak early diastolic velocity/peak late diastolic velocity (E/A)assessed by echocardiography before and after treatment, and total effective rate were compared between two group.Results:Total effective rate of Lrh-BNP group was sig- nificantly higher than that of routine treatment group (92.3% vs.80.0% ,P0.05 all);after treatment,com- pared with routine treatment group,there were significant rise in LVEF [(50.2±16.3)% vs.(59.4±14.1)%],SV [(39.5±10.4)ml vs.(48.3±12.5)ml],CI [(3.7±1.1)L min-1 m-2 vs.(4.6±1.4)L min-1 m-2 ]and E/A [(1.0±0.5)vs.(1.3±0.7)]in Lrh-BNP group,P0.05);治疗后,与常规治疗组比较,Lrh-BNP组LVEF[(50.2±16.3)%比(59.4±14.1)%]、SV[(39.5±10.4)ml比(48.3±12.5)ml]、CI[(3.7±1.1)L·min-1·m-2比(4.6±1.4)L·min-1·m-2]、E/A[(1.0±0.5)比(1.3±0.7)]显著升高(P均<0.05).结论:Lrh-BNP治疗应激性心肌病合并急性泵衰竭有明显疗效.

  7. Correlation between heart rate variability and brain natriuretic peptide in patients with persistent atrial fibrillation%持续性心房颤动患者心率变异性与脑钠尿肽的关系

    Institute of Scientific and Technical Information of China (English)

    李宏松; 石来新; 卢英民; 韦彩雯; 宋蕾; 李志华; 蔡振东

    2012-01-01

    目的:探讨持续性心房颤动患者心率变异性与脑钠尿肽(BNP)的相关性.方法:入选45例持续性心房颤动患者,20例正常对照组.行24小时动态心电图检查,检测心率变异性时域指标,并行BNP测定,再分析以上两者的相关性.结果:持续性房颤患者与对照组比较,心率增快,心率变异性时域指标SDNN、RMSSD、PNN50显著增加(P<0.01);平均RR间期(RINNT)实测值与BNP呈负相关;以平均心率矫正后的有关心率变异时域指标RMSS-DDdiff和PNN50Ddiff与BNP呈正相关.结论:持续性心房颤动患者心率变异性时域参数增加,BNP受心率和心率变异性改变的影响.%AIM: To investigate the correlation between heart rate variability and brain natriuretic peptide (BNP) in patients with persistent atrial fibrillation (AF). METHODS: Forty-five patients with persistent AF were placed into one group and 20 patients without persistent AF were placed in the normal control group. Twenty-four hour ECG was monitored for the time domain indexes of heart rate variability, and plasma BNP concentration was tested. Correlation between the time domain indexes and plasma BNP concentration was analyzed. RESULTS: In patients with persistent AF, the heart rate increased and heart rate variability time domain indexes (SDNN, RMSSD and PNN50) increased significantly (P < 0. 01). The actual RINNT was negatively correlated with plasma BNP concentration. After correction with the average heart rate, heart rate variability time domain indexes (RMSSDDdiff and PNN50Ddiff) were positively correlated with BNP concentration. CONCLUSION: In patients with persistent AF, the time domain parameters of heart rate variability increase and plasma BNP concentration is affected by the heart rate and the changes in heart rate variability.

  8. Selection of trkB-binding peptides from a phage-displayed random peptide library

    Institute of Scientific and Technical Information of China (English)

    马仲才; 吴晓兰; 曹明媚; 潘卫; 朱分禄; 陈景山; 戚中田

    2003-01-01

    Brain-derived neurotrophic factor (BDNF) shows potential in the treatment of neurodegenerative diseases, but the therapeutic application of BDNF has been greatly limited because it is too large in molecular size to permeate blood-brain barrier. To develop low-molecular-weight BDNF-like peptides, we selected a phage-displayed random peptide library using trkB expressed on NIH 3T3 cells as target in the study. With the strategy of peptide library incubation with NIH 3T3 cells and competitive elution with 1 υg/mL of BDNF in the last round of selection, the specific phages able to bind to the natural conformation of trkB and antagonize BDNF binding to trkB were enriched effectively. Five trkB-binding peptides were obtained, in which a core sequence of CRA/TXφXXφXXC (X represents the random amino acids, φ represents T, L or I) was identified. The BDNF-like activity of these five peptides displayed on phages was not observed, though all of them antagonized the activity of BDNF in a dose-dependent manner. Similar results were obtained with the synthetic peptide of C1 clone, indicating that the 5 phage-derived peptides were trkB antagonists. These low-molecular-weight antagonists of trkB may be of potential application in the treatment of neuroblastoma and chronic pain. Meanwhile, the obtained core sequence also could be used as the base to construct the secondary phage-displayed peptide library for further development of small peptides mimicking BDNF activity.

  9. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  10. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  11. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  12. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  13. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  14. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  15. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  16. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  17. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  18. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  19. Associativity of subclinical thyroid dysfunction with serum NT-pro-brain natriuretic peptide%亚临床甲状腺功能异常与血清NT-pro-BNP水平相关性的研究

    Institute of Scientific and Technical Information of China (English)

    金丹玲; 许艳玲; 刘兆军

    2012-01-01

    目的:研究亚临床甲状腺功能异常患者血浆中NT-pro-BNP浓度的差异.方法:选取2002年至2010年亚临床甲状腺功能异常住院患者122例,年龄23~ 82岁.其中男性54例,女性68例.根据血清TSH水平分为:A组,亚临床甲减1组(TSH4.5~9.9 mU·L-1,n=26);B组,亚临床甲减2组(TSH≥10 mU·L-1,n =30);C组,亚临床甲亢1组(TSH 0.1 ~0.44 mU·L-1,n=24);D组,亚临床甲亢2组(TSH<0.1 mU·L-1,n =21);E组,甲状腺功能正常组(TSH 0.45 ~4.5 mU·L-1,n=21).测定每组患者血清NT-pro-BNP浓度.结果:D组血清NT-pro-BNP浓度较E组增高(95% CI:57.8477~ 168.5159,P<0.05),较C组显著增高(95% CI:11.5080~ 138.5656,P<0.05).A组和B组血清NT-pro-BNP浓度较E组无明显差异(P>0.05).受试者体质量指数、空腹血糖水平、左室质量指数与血浆NT-pro-BNP浓度没有相关性.结论:亚临床甲亢患者TSH <0.1 mU·L-1时,心力衰竭的发生风险明显增加.%Objective: To evaluate the serum NT- pro- brain natriuretic peptide ( NT- pro- BNP) in different subgroup of the subclinical thyroid dysfunction. Methods: 122 patients to be in hospital in the department of endocrinology and cardiology from the year 2002 to 2010, who, on the basis of plasma levels of TSH, were divided into subclinical hypothyroidism 1 group (TSH 4. 5-9. 9 mU·L-1 ,n =26) , subclinical hypothyroidism 2 group (TSH ≥ 10 mU · L-1, n = 30 ) , subclinical hyperthyroidism 1 group ( TSH 2s 0. 1 , < 0. 45 mU · L -1 , n = 24 ) , subclinical hyperthyroidism 2 group ( TSH < 0. 1 mU·L-1,n =21) , control subjects with normal thyroid profile TSH (0.45-4.5 mU·L-1 ,n =21) , to evaluate the serum NT-pro-BNP. Results: Compared to control subjects, subclinical hyperthyroidism were characterized by higher serum NT- pro- BNP, this increase was particularly pronounced in subclinical hyperthyroidism 2 ( TSH < 0. 1 mU · L -1 ) compared to subelinical hyperthyroidism 1 ( TSH ≥ 0. 1 , <0. 45 mU·L-1), serum NT-pro-BNP did not

  20. Clinical application of plasma brain natriuretic peptid to assess the dry weight of hemodialysis patient%血浆脑钠肽在评估血液透析患者干体重中的应用价值

    Institute of Scientific and Technical Information of China (English)

    王世进; 笪义生

    2012-01-01

    目的:观察血液透析(HD)患者调整干体重前后血浆脑钠肽(BNP)水平的变化,探讨BNP评估HD患者干体重的应用价值.方法:根据透析患者胸部X线片心胸比(CRT)、血压、下腔静脉内径(IVCD)、评估50例血液透析患者干体重,将患者分为干体重未达标组(A组)与达标组(B组)各25例,且将A组经过4周逐渐增加透析脱水量下调干体重达到临床干体重(D组).同时选取25名健康体检合格成人作为对照组(C组),测定血压、CRT、IVCD/体表面积(VCD)、BNP等数值.结果:A组BNP、CRT和VCD水平均显著高于B、C和D组(P<0.01),B、C和D组BNP、CRT和VCD水平差异均无统计学意义(P>0.05),且A组患者干体重调节前后BNP水平变化和VCD值、CRT之间均呈正相关关系(P<0.01).结论:BNP作为HD患者超水平负荷的指标,评估干体重有一定价值.%Objective: To observe the plasma brain natriuretic peptid ( BNP) levels of hemodialysis ( HD ) patient before and after adjustment of dry weight and explore its value in evaluating dry weight. Methods: Fifty HD patients were divided into group A ( no-reaching the dry weight standard, 25 cases) and group B ( reaching the dry weight standard, 25 cases) according to the dry weight evaulated by cardiac thoracic rate (CRT) , blood pressure, body weight and the inferior vena cava width(IVCD). The dry weight of partial patients from group A were adjusted to reach the clinical dry weight by increasing the dialysis dehydrated level for 4 weeks, which was divided into group D. Twenty-five healthy persons were divided into group C(control group) ,which blood pressure, CRT, VCD and BNP were measured. Results: The levels of BNP, CRT and VCD of group A were significantly higher than that of group B, C and D( P 0. 05 ) . BNP level changes of group A before and after adjustment of dry weight were positively related to its value of VCD and CRT( P < 0. 01) . Conclusions: BNP can be used as the water load index of HD patients

  1. Serum sodium levels of heart failure and its influence on plasma renin-angiotensin-aldosterone system and brain natriuretic peptide levels%心力衰竭血钠水平对 RAAS 及 BNP 水平的影响

    Institute of Scientific and Technical Information of China (English)

    王玉东; 任松涛; 蔡青云

    2014-01-01

    Objective To study the correlation between serum sodium levels of heart failure and plasma renin-angiotensin-aldosterone system( PAAS) and brain natriuretic peptide(BNP) levels . Methods 122 122 patients with heart failure were divided into control ( serum sodium concentration<135 mmol/L ,57 cases) and observation group ( serum sodium concentration≥135 mmol/L , 65 cases) according to serum sodium levels . PRA , Ang Ⅱ , ALD and BNP levels of two groups were compared and analyzed , the correlation between serum sodium levels and levels of PRA ,AngⅡ ,ALD and BNP were analyzed by Pearson correlation analysis . Results Levels of PRA , Ang Ⅱ ,ALD and BNP of observation group were higher than that in control group significantly( P < 0 .05 ) .Pearson correlation analysis showed , serum sodium levels was positively correlated with levels of PRA , Ang Ⅱ , ALD and BNP( P <0 .05 ) .Conclusion Low level serum sodium of heart failure promotes the release of PRA , Ang , ALD and BNP , serum sodium levels is positively correlated with levels of PRA , Ang Ⅱ , ALD and BNP .%目的:研究心力衰竭患者血钠水平与血浆肾素-血管紧张素-醛固酮系统(RAAS)及脑钠肽之间(BNP)的相关性。方法选择我院收治的122例心力衰竭患者,根据血钠水平分为对照组(血清钠离子浓度<135 mmol/L ,57例)和观察组(血清钠离子浓度≥135 mmol/L ,65例),对2组患者的肾素(PRA)、血管紧张素(AngⅡ)、醛固酮(ALD)及BNP水平进行比较分析,并对血钠水平与AngⅡ、ALD及BNP水平的相关性采用 Pearson相关分析。结果观察组的PRA、AngⅡ、ALD及BNP水平显著高于对照组,差异具有统计学意义(P <00.5),通过 Pearson相关分析可见,患者的血钠水平与PRA、AngⅡ、ALD及BNP水平均呈负相关( P <00.5)。结论心力衰竭患者血钠水平低时能促进PRA、AngⅡ、ALD及BNP的释放,且血钠水平

  2. 脑钠肽与不稳定型心绞痛患者左心功能相关性研究%Relationship between brain natriuretic peptide and left heart function in patients with unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    杨波; 夏勇

    2012-01-01

    Objective To observe the changing rule of plasma level of brain natriuretic peptide (BNP) and left ventricular end-diastolic pressure (LVEDP)in patients with unstable angina pectoris ( UAP) ,and explore the correlation between the changes of left heart function and BNP. Methods Fifty-seven cases who underwent coronary angiography( CAC) examination were included. Twelve cases with normal CAG examination results as control group, forty -five patients with UAP were divided into grade Ⅰ group(n = 16) ,grade Ⅱ group(n = 14) and grade Ⅲ group(n = 15) according to the class of Braunwald. The left atrial dianieter(LAD) ,left ventricular end-diastolic diameter( LVEDd), left ventricular posterior wall thickness( LVP-WT) ,intervenlricular septal thickness( IVST) ,left ventricular ejection fraction( LVEF)and E/A were detected in all cases by Doppler echocardiography. The value of LVEDP was detected by record left ventricular pressure curves in all cases. The plasma concentration of BNP was measured by radioimmunoassay. Results There were significant differences in the plasma levels of BNP and LVEDP in control group,grade Ⅰ, Ⅱ, Ⅲ groups(P 0.05). The plasma level of BNP was obviously correlated with LVEDP in all cases ( r = 0.756, P < 0.01). Conclusion The level of BNP could reflect the severity of cardiac ischemia in patients with UAP.it could reflect the severities of congestive heart failure to some extend.%目的 研究血浆脑钠肽(BNP)水平与左心室舒张末期压力(LVEDP)在不稳定型心绞痛(UAP)患者中的变化规律,探讨左心功能的变化与BNP变化的相关性.方法 选择57例冠状动脉造影(CAG)检查者为研究对象,CAG检查正常者12例作为对照组,45例UAP患者按Braunwald分级分为Ⅰ级组(16例)、Ⅱ级组(14例)和Ⅲ级组(15例).所有患者采用多普勒超声心动图检测左心房前后径(LAD)、左心室舒张末期内径(LVEDd)、左心室后壁厚度(LVPWT)、室间隔厚度(IVST)、左心室射血分

  3. 冻干重组人脑利钠肽治疗充血性心力衰竭疗效观察%Clinical efficacy of lyophilized recombinant human brain natriuretic peptide in the treatment of patients with congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    苏素缺; 郑朝霞; 代东艳; 王鹏

    2014-01-01

    目的 探讨冻干重组人脑利钠肽治疗充血性心力衰竭的临床疗效和安全性.方法 选择120例充血性心力衰竭患者,按照随机数字分组法分为两组,观察组58例患者采用冻干重组人脑利钠肽进行治疗,对照组62例患者采用硝普钠进行治疗,比较两组患者的临床疗效、超声心动图指标、血流动力学指标的变化情况以及不良反应的发生情况.结果 治疗后,观察组总有效率为91.37%,明显高于对照组(x2=4.23,P<0.05),观察组治疗后的LVEF、氨基末端脑钠肽前体水平分别为(59.0±8.2)%和(535.4±123.8) ng/L,其改善程度较对照组更为明显(P<0.05),两组不良反应的发生率基本相当(P>0.05).结论 冻干重组人脑利钠肽在治疗充血性心力衰竭具有十分显著的疗效,其安全可靠.%Objective To investigate the clinical efficacy and safety of lyophilized recombinant human brain natriuretic peptide(rhBNP) in the treatment of patients with congestive heart failure (CHF).Methods 120 CHF patients were randomly divided into two groups.58 cases in the observation group were given lyophilized rhBNP,and 62 patients in the control group were given sodium nitroprusside.The clinical effect,changes of echocardiographic indicators and hemodynamic parameters,adverse reactions were observed.Results After treatment,the total effective rate of the observation group was 91.37%,which was significantly higher than that of the control group(x2 =4.23,P < 0.05).The LVEF and NT-proBNP levels in observation group were (59.0 ± 8.2)% and (535.4 ± 123.8)ng/L,which had higher improvement than control group (P < 0.05).The incidence rate of adverse reactions between the two groups had no significant difference (P> 0.05).Conclusion Lyophilized rhBNP in the treatment of CHF has significant effect,and it is worthy of clinical application and promotion.

  4. 脓毒症休克与血清氨基末端B型利钠肽前体研究进展%Research Progress on N-terminal Pro-brain Natriuretic Peptide in Septic Shock

    Institute of Scientific and Technical Information of China (English)

    商娜; 张源波; 周荣斌; 杨萌

    2013-01-01

    脓毒症休克是极为常见的危重病,病情凶险,病死率高达30%~70%.近年来,随着早期目标指导性治疗(EGDT)在重症领域的应用,其病死率有了很大改善.目前,临床医师多数根据血流动力学指标的异常指导治疗和判断预后,但血流动力学指标的获得操作复杂、技术要求高,且具有一定的滞后性.国内外学者一直致力于探索敏感性和特异性较高的生物标记物--血清氨基末端B型利钠肽前体(NT-proBNP),希望为脓毒症休克的早期积极干预提供参考依据.研究发现,脓毒症休克时NT-proBNP升高有多种机制参与,NT-proBNP水平的变化可指导脓毒症休克患者的治疗和判断预后.NT-proBNP检测简便迅速,具有广阔的临床应用前景.本文主要结合国内外文献探讨脓毒症休克时NT-proBNP变化机制及其临床应用.%Septic shock is a very common disease and its mortality rate is as high as 30% to 70% . In recent years, with the widely application of early goal - directed therapy ( EGDT ) in intensive illnesses, the mortality rate was greatly reduced. Currently, hemodynamic parameters are used to guide treatment and predict prognosis, but these parameters can only be obtained by skilled operators and are time - consuming. Domestic and foreign scholars have been dedicated to exploring a biological marker with high sensitivity and specificity, that is, serum amino - terminal pro - brain natriuretic peptide ( NT - proBNP ), which can provide reference for the early intervention and prediction of patients with septic shock. Studies have found that multiple mechanisms can cause the changes of NT - proBNP level in septic shock, and these changes can guide treatment and prognosis of patients with septic shock. Besides, the detection of NT - proBNP is simple and fast, so its clinical application is promising. This paper is aimed to introduce mechanisms of NT - proBNP change in septic shock and its clinical application.

  5. Determinação do peptídeo natriurético cerebral humano em portadores da doença de Chagas Measurement of human brain natriuretic peptide in patients with Chagas' disease

    Directory of Open Access Journals (Sweden)

    Railton Bezerra de Melo

    2005-02-01

    Full Text Available OBJETIVO: Determinar os níveis séricos do peptídeo natriurético cerebral (PNB em pacientes com cardiopatia chagásica crônica e em indivíduos com sorologia positiva para doença de Chagas sem comprometimento cardíaco, e correlacionar os níveis de PNB com o grau de comprometimento cardíaco, dimensões cardíacas, presença de marcapasso e fração de ejeção. MÉTODOS: Concentrações séricas de PNB foram determinadas através do Triage® - BNP Test, produzido pela BIOSITE®. Foi avaliado o PNB sérico de 25 indivíduos do ambulatório de doença de Chagas do Hospital Universitário Oswaldo Cruz, distribuídos em 2 grupos, um, G1; composto por 13 portadores de sorologia positiva para doença de Chagas, assintomáticos e sem cardiopatia detectável pelo eletrocardiograma, radiografia do tórax e ecocardiograma, o outro, G2; por 12 portadores da doença de Chagas com comprometimento cardíaco. RESULTADOS: Níveis significativamente mais elevados de PNB foram detectados nos pacientes chagásicos com comprometimento cardíaco: (G1=4,4±4,4 pg/ml, G2=293,0±460,2 pg/ml pOBJECTIVE: To measure the serum levels of brain natriuretic peptide (BNP in patients with chronic chagasic heart disease and in individuals with positive serology for Chagas' disease and no heart impairment, and to correlate the serum BNP levels with the degree of cardiac impairment, cardiac dimensions, presence of a pacemaker, and ejection fraction. METHODS: Serum BNP concentrations were determined by use of the Triage - BNP Test produced by BIOSITE. Serum BNP was assessed in 25 patients from the Chagas' disease outpatient clinic of the Hospital Universitário Oswaldo Cruz, who were divided into 2 groups as follows: 1 G1 - comprising 13 assymptomatic patients with positive serology for Chagas' disease and no heart disease detectable on electrocardiography, chest X-ray, and echocardiography; and 2 G2 - comprising 12 patients with Chagas' disease and heart impairment. RESULTS

  6. 川崎病患儿心型脂肪酸结合蛋白和脑利钠肽的变化及与心功能的关系%Changes of serum heart type fatty acid binding protein and brain natriuretic peptide and their clinical significance in children with Kawasaki disease

    Institute of Scientific and Technical Information of China (English)

    王金菊; 陈宗波; 王文棣

    2015-01-01

    Objective To explore the serum levels changes of heart-type fatty acid-binding protein and brain natriuretic peptide in children with Kawasaki disease,as well as their links with the heart function. Methods A total of 53 children with Kawasaki disease admitted to our hospital from February 2008 to March 2012 were selected and at the same time 50 healthy controls were randomly selected. The serum levels for the children in acute phase,recovery period of Kawasaki disease and control group children were determined by en-zyme-linked immnoabsorbent assay. The internal diameter of coronary artery,LVEF,LVSF,CI and E/A of chil-dren were measured by two-dimensional echocardiography. Results The heart-type fatty acid-binding protein and brain natriuretic peptide concentrations of children with Kawasaki disease in acute stage[(18. 23 ± 13. 81) ng/ml,(517. 2 ±213. 2) pg/ml] were higher than those in recovery stage[(6. 29 ± 1. 26) ng/ml,(92. 1 ± 46. 0) pg/ml](P<0. 05). They were also higher for children in acute stage than those of control group[(6. 26 ± 1. 60) ng/ml,(37. 6 ± 7. 6) pg/ml]. The LVEF,LVSF,CI of Kawasaki disease for children in acute stage were lower than those in recovery phase[(60. 3 ± 3. 6)% vs. (64. 8 ± 4. 3)%,(30. 6 ± 2. 5)% vs. (34. 9 ± 1. 9)%,(3. 1 ± 0. 3)% vs. (3. 5 ± 0. 3)%]. Linear correlation analysis showed the heart-type fatty acid-binding protein and brain natriuretic peptide′concentrations in Kawasaki disease were negatively correlated with LVEF (P<0. 05). The heart-type fatty acid-binding protein′positive rates were also higher than brain natriuretic peptide for the children in acute and recovery phase. Conclusion The heart-type fatty acid-binding protein and brain na-triuretic peptide could be used as the biochemical markers for myocardial damage of children with Kawasaki dis-ease. The heart-type fatty acid-binding protein was more significant than brain natriuretic peptide. The heart-type fatty acid-binding protein and brain

  7. Phage display:development of nanocarriers for targeted drug delivery to the brain

    Institute of Scientific and Technical Information of China (English)

    Babak Bakhshinejad; Marzieh Karimi; Mohammad Khalaj-Kondori

    2015-01-01

    The blood brain barrier represents a formidable obstacle for the transport of most systemati-cally administered neurodiagnostics and neurotherapeutics to the brain. Phage display is a high throughput screening strategy that can be used for the construction of nanomaterial peptide libraries. These libraries can be screened for ifnding brain targeting peptide ligands. Surface func-tionalization of a variety of nanocarriers with these brain homing peptides is a sophisticated way to develop nanobiotechnology-based drug delivery platforms that are able to cross the blood brain barrier. These efifcient drug delivery systems raise our hopes for the diagnosis and treatment of various brain disorders in the future.

  8. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  9. Prognostic Value of Brain Natriuretic Peptide in Puerperant be Complicated by Acute Congestive Heart Failure%脑钠肽对判定围生期急性充血性心力衰竭预后的临床意义

    Institute of Scientific and Technical Information of China (English)

    金善律; 赵薇; 张京晓

    2011-01-01

    目的 观察血浆脑钠肽与围生期充血性心力衰竭患者预后的关系.方法 我院ICU科2009年1月-2010年6月收治的41例剖宫产终止妊娠后并发急性充血性心力衰竭患者,终止妊娠后第1天均行肝肾功能、脑钠肽、心电图及超声心动图检查;30 例剖宫产终止妊娠后无充血性心力衰竭患者作为对照组.结果 与结论 剖宫产终止妊娠合并急性充血性心力衰竭患者血浆脑钠肽浓度较对照组高(P<0.001 ),血浆脑钠肽浓度越高,患者入住ICU的时间则越长,其病死率也越高.%Objective Through the detection of concentration of brain natriuretic peptide(BNP)in blood plasma in the women who terminate pregnancy by utedrine-incision delivery and complicated by congestive heart failure,we observate the association between the prognosis and BNP.Methods 41 patients enrolled in the study who terminated pregnancy by uterine-incision delivery and complicated by congestive heart failure we have treated in the ICU department during2009.01-2010.06. We detectded alanine aminotransferase(Alt),aspartate aminotransferase(Ast),creatinine,urea,electrocardiogram,ultrasonic cardiogram on the first day after the delivery.Other30 pregnancy women with mormal heart funtion were get by control group.Results and Conclusion The concentration of brain natriuretic peptide in the patients who complicated by congestive heart failure was obviously raise up than the control group,and the concentration of brain natriuretic peptide prognosticate the length of stay and case fatality rate.

  10. Clinical Observation on Application of Tiroifban and Recombinant Human Brain Natriuretic Peptide in the Treatment of Acute Myocardial Infarction Complicated With Heart Failure%探讨急性心肌梗死合并心力衰竭应用替罗非班及重组人脑利钠肽的临床观察

    Institute of Scientific and Technical Information of China (English)

    李艳萍

    2016-01-01

    Objective To investigate the clinical effect of tirofiban and recombinant human brain natriuretic peptide for the treatment of patients with acute myocardial infarction complicated with heart failure.Methods In our hospital from September 2013 to August 2015, 168 cases of patients with AMI-HF were divided into two groups. The control group and the research group had 84 cases. AMI-HF baseline treatment was used in the two groups. The control group increased urokinase thrombolytic therapy, the study group used tirofiban and treatment with recombinant human brain natriuretic peptide. The adverse reactions and treatment of the two groups were compared and analyzed.ResultsThe effective rate of clinical treatment in the study group was 96.43%, and the effective rate of the control group was 83.33%. Conclusion Acute myocardial infarction complicated with heart failure patients accept for the effect of tirofiban and recombinant human brain natriuretic peptide in patients with relatively good, with high security.%目的:探讨替罗非班和重组人脑利钠肽治疗急性心肌梗死合并心衰患者的临床效果。方法选取2013年9月~2015年8月我院收治的168例AMI-HF患者进行了分组研究,对照组和研究组,每组各84例。两组患者均采用AMI-HF基线治疗。对照组增加尿激素酶溶栓治疗,研究组采用替罗非班及重组人脑利钠肽治疗。比较分析两组患者的不良反应和治疗情况。结果研究组患者的临床治疗有效率为96.43%,对照组的临床治疗有效率为83.33%。结论采用替罗非班及重组人脑利钠肽治疗急性心肌梗死合并心衰患者效果显著,具有较高的安全性。

  11. BDNF pro-peptide regulates dendritic spines via caspase-3.

    Science.gov (United States)

    Guo, J; Ji, Y; Ding, Y; Jiang, W; Sun, Y; Lu, B; Nagappan, G

    2016-06-16

    The precursor of brain-derived neurotrophic factor (BDNF) (proBDNF) is enzymatically cleaved, by either intracellular (furin/PC1) or extracellular proteases (tPA/plasmin/MMP), to generate mature BDNF (mBDNF) and its pro-peptide (BDNF pro-peptide). Little is known about the function of BDNF pro-peptide. We have developed an antibody that specifically detects cleaved BDNF pro-peptide, but not proBDNF or mBDNF. Neuronal depolarization elicited a marked increase in extracellular BDNF pro-peptide, suggesting activity-dependent regulation of its extracellular levels. Exposure of BDNF pro-peptide to mature hippocampal neurons in culture dramatically reduced dendritic spine density. This effect was mediated by caspase-3, as revealed by studies with pharmacological inhibitors and genetic knockdown. BDNF pro-peptide also increased the number of 'elongated' mitochondria and cytosolic cytochrome c, suggesting the involvement of mitochondrial-caspase-3 pathway. These results, along with BDNF pro-peptide effects recently reported on growth cones and long-term depression (LTD), suggest that BDNF pro-peptide is a negative regulator of neuronal structure and function.

  12. Developing a Dissociative Nanocontainer for Peptide Drug Delivery

    Directory of Open Access Journals (Sweden)

    Patrick Kelly

    2015-10-01

    Full Text Available The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.

  13. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  14. Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

    Directory of Open Access Journals (Sweden)

    Anna-Sophia Wisser

    2010-01-01

    Full Text Available Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK, bombesin, desacyl ghrelin, peptide YY (PYY, as well as glucagon-like peptide (GLP. Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite.

  15. Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

    Science.gov (United States)

    Wisser, Anna-Sophia; Habbel, Piet; Wiedenmann, Bertram; Klapp, Burghard F.; Mönnikes, Hubert; Kobelt, Peter

    2010-01-01

    Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite. PMID:20798884

  16. Interactions of gastrointestinal peptides: ghrelin and its anorexigenic antagonists.

    Science.gov (United States)

    Wisser, Anna-Sophia; Habbel, Piet; Wiedenmann, Bertram; Klapp, Burghard F; Mönnikes, Hubert; Kobelt, Peter

    2010-01-01

    Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite.

  17. Topical peptides as cosmeceuticals

    Directory of Open Access Journals (Sweden)

    Varadraj Vasant Pai

    2017-01-01

    Full Text Available Peptides are known to have diverse biological roles, most prominently as signaling/regulatory molecules in a broad variety of physiological processes including defense, immunity, stress, growth, homeostasis and reproduction. These aspects have been used in the field of dermatology and cosmetology to produce short, stable and synthetic peptides for extracellular matrix synthesis, pigmentation, innate immunity and inflammation. The evolution of peptides over the century, which started with the discovery of penicillin, has now extended to their usage as cosmeceuticals in recent years. Cosmeceutical peptides may act as signal modulators of the extracellular matrix component, as structural peptides, carrier peptides and neurotransmitter function modulators. Transdermal delivery of peptides can be made more effective by penetration enhancers, chemical modification or encapsulation of peptides. The advantages of using peptides as cosmeceuticals include their involvement in many physiological functions of the skin, their selectivity, their lack of immunogenicity and absence of premarket regulatory requirements for their use. However, there are disadvantages: clinical evidence for efficacy is often weak, absorption may be poor due to low lipophilicity, high molecular weight and binding to other ingredients, and prices can be quite high.

  18. Protective effect of recombinant human brain natriuretic peptide on acute renal injury induced by endotoxin in canines%rhB NP对内毒素介导的犬急性肾损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    李牧; 刘岩; 李辉

    2014-01-01

    干预组比较,血清HMGB-1水平显著性减少(P<0.05)。结论 rhBNP可以有效减轻内毒素介导的犬肾组织损伤,改善肾功能,并降低SVRI,且其治疗作用呈剂量-效应关系;rhBNP还能有效降低脓毒症犬血清HMGB-1水平,可能与晚期炎症因子HMGB1水平的降低有关。%Objective To observe the influence of recombinant human brain natriuretic peptide(rhBNP)on serum HMGB1 levels in canines'acute renal injury induced by endotoxin and explore its protective role of rhBNP in protecting canines'kidney against acute renal injury.Methods A total of 20 healthy dogs were randomly divided into four groups:blank group,sepsis shock group,low-dose intervention group and high dose intervention group, and there were 5 rats in each group.After establishing the model of canines'sepsis shock induced by endotoxin,15 canines (besides blank group)were randomly divided into 3 groups.As follows,5 μg/kg rhBNP was given to the low-dose intervention group,10μg/kg rhBNP was given to the high-dose intervention group.But nothing was given to control group.Systemic vascular resistance index(SVRI)at 0 h,2 h,4 h,8 h,12 h were observed by PICCO instrument.High mobility group box 1 protein (HMGB-1)and creatinine(CR)in blood samples at each time point were detected.After 12 hours,kidney samples were taken for histological examination.Results The results revealed that some renal tubulars epithelial cell were swelled,some epithelial cells were atrophy and interstitial cells swelled in control group under the light microscope.Kidney pathology score was 2-3.But these changes were improved in low-and high-dose intervention groups,and there were no significant difference in the latter two groups,kidney of both groups pathology score were 1-2.Compared with control group at the same point,CR of blood serum were significantly decreased in low-dose intervention group at 8 h,12 h(P<0.01), and high-dose intervention group significantly decreased at 4 h,8 h,12 h(P<0.01).Compared with

  19. Observation of the Effect of Lyophilized Recombinant Human Brain Natriuretic Peptide Jointing Low-dose Dobutamine Used to Refractory Heart Failure%人冻干重组脑利钠肽联合小剂量多巴酚丁胺对顽固性心力衰竭的疗效观察

    Institute of Scientific and Technical Information of China (English)

    黄瑞娜; 吴铿; 冼倩; 陈铭林; 李上海; 李腾; 叶少强; 游琼

    2013-01-01

    Objective To evaluate the effect of the patients with Refractory heart failure using Lyophilized recombinant human brain natriuretic peptide jointing low-dose Dobutamine. Methods 120 patients with Refractory heart failure were randomly divided into A group(n=40), B group(n=40) and C group(n=40), A group was treated with conventional-dose Dobutamine, B group was treated with Lyophilized recombinant human brain natriuretic peptide. C group was treated with Lyophilized recombinant human brain natriuretic peptide jointing low-dose Dobutamine. Three groups were compared the effect of heart failure treatment, LAD,LVEDD,LVEF and plasma BNP level.Results Compared with A group and B group, C group’s treatment of arrhythmia get best results. Compared with before treatment,three group’s LAD ,LVEDD and plasma BNP level decreased,E/A improved, the effect of group C is especially obvious. Conclusion It is effective and safe for the patients with Refractory heart failure to use Lyophilized recombinant human brain natriuretic peptide jointing low-dose Dobutamine.%目的:对顽固性心力衰竭患者使用人冻干重组脑利钠肽联合小剂量多巴酚丁胺的疗效进行评估。方法选取顽固性心力衰竭患者120例,随机分为A组、B组和C组各40例,常规基础治疗上,A组给予常规剂量多巴酚丁胺,B组给予人冻干重组脑利钠肽,C组给予人冻干重组脑利钠肽联合小剂量多巴酚丁胺。比较三者临床疗效、左房内径、左心室舒张期末径、左心室射血分数、血浆脑利钠肽等指标。结果 C组对顽固性心力衰竭的疗效明显高于A组、B组;与治疗前比较,三组在治疗后72h左室内径减小,左室射血分数提高,血浆BNP水平下降,但以C组效果尤佳。结论人冻干重组脑利钠肽联合小剂量多巴酚丁胺治疗顽固性心力衰竭效果显著,副作用小。

  20. Significance of Changes of Brain Natriuretic Peptide in Children with Rheumatic Heart Disease%风湿性心脏病患儿血浆脑利钠肽水平变化的意义

    Institute of Scientific and Technical Information of China (English)

    孙裕平; 王文棣; 马少春; 郑兴厂; 王金菊; 魏超平

    2012-01-01

    目的 观察风湿性心脏病患儿血浆脑利钠肽(BNP)水平的变化,探讨其在风湿热(RF)并心脏病变患儿中的诊断价值.方法 选择RF患儿20例(RF组),包括风湿性心脏病患儿11例(心脏病变组),无心脏病变患儿9例(无心脏病变组).同时选择20例健康儿童作为健康对照组.采用ELISA测定各组血浆BNP、肌钙蛋白I(cTnI)水平,并行心脏彩色多普勒超声及ECG检查.健康对照组随机采血1次,测定血浆BNP和cTnI水平.应用SPSS 11.5软件进行统计学分析.结果 RF组患儿血浆BNP、cTnI水平均明显高于健康对照组(Pa<0.01);心脏病变组血浆BNP水平较无心脏病变组明显升高(P<0.01),cTnI水平二组比较差异亦有统计学意义(P<0.05);BNP异常升高率显著高于cTnI(x2=14.19,P<0.01)及ECG(x2=10.23,P<0.01),cTnI异常率与ECG异常率比较差异无统计学意义(x2=1.37,P>0.05).心脏病变组患儿BNP与cTnI水平呈显著正相关(r=0.32,P<0.05).结论 BNP在风湿性心脏病患儿中异常增高,与cTnI呈正相关,且较cTnI、ECG灵敏度高.BNP、cTnI二者结合对RF并心脏病变的诊断具有重要意义.%Objective To observe the changes of brain natriuretic peptide(BNP) in children with rheumatic fever(RF) disease,and explore its diagnostic value in rheumatic heart disease. Methods Twenty RF children( RF group) were collected,including 11 patients combined with heart disease ( heart disease group) and 9 patients without heart disease (non - heart disease group) ;Twenty healthy children were obtained as healthy control group. The plasma level of BNP and cardiac troponin I(cTnl) were measured by using enzyme - linked immu-nosorbent assay; Two - dimensional echocardiography and ECG were used for all the patients. The plasma levels of BNP and cTnl were randomly measured once in healthy control group. SPSS 11.5 software was used to analyze the data. Results BNP and cTnl were significantly higher in RF group than those in healthy

  1. 血浆B型脑钠肽水平在慢性肺源性心脏病诊断中的作用%Role of plasma B-type brain natriuretic peptide level in diagnosis of chronic cor pulmonale

    Institute of Scientific and Technical Information of China (English)

    吴颖; 高蔚; 施斌

    2016-01-01

    Objective To investigate the diagnostic value of plasma B-type brain natriuretic peptide(BNP) level in chronic cor pulmonale by detecting plasma BNP level in the patients with chronic dyspnea. Methods Two hundreds and sixty-four inpa-tients with chronic dyspnea in the respiration department and cardiology department of our hospital from March 2014 to April 2015 were selected and divided into the simple pulmonary disease group (100 cases),chronic cor pulmonale group (89 cases) and left cardiac failure group(75 cases) based on the clinical data,clinical manifestations and related detection results. The levels of plasma BNP in each group were measured by immunofluorometric assay. Chest X-ray and electrocardiogram(EKG) examinations were also performed in all the cases. Results (1)The plasma BNP levels in the simple pulmonary disease group,cor pulmonale group and left cardiac failure group were (83.26±14.84),(330.24±38.10),(1 180.73±100.51)pg/mL respectively,the differences in inter-group pairwise comparison showed statistical significance(P<0.05).(2)In plasma BNP level for diagnosing chronic cor pulmonale,the area under the receiver operating characteristic(ROC) curve was 0.871,the optimal diagnostic cut-off was 95 . 00 pg/mL and the accuracy was 83.5%;the area under ROC curve for diagnosing left cardiac failure was 0.896 ,the optimal di-agnostic cut-off was 310.50 pg/mL and the accuracy was 84.2%. (3) In the optimal cut-off values of chest X-ray,EKG and BNP, their accuracies for the single diagnosis of chronic cor pulmonale were 66.7%,72.7%and 83.5%respectively,which for single di-agnosis of left cardiac failure were 64.3%,70.1%and 84.2%respectively. Conclusion (1)BNP is involved in the pathophysio-logic process of right cardiac insufficiency and left cardiac failure in cor pulmonale and may serve as an indicator of early diagno-sis of cardiac dysfunction.(2)The diagnostic value of clinical suspected diagnosis combined plasma BNP level detection in chronic cor

  2. 血清脑利钠肽检测在肺心病患者中的应用价值%The value of serum brain natriuretic peptide in chronic pulmonary heart disease

    Institute of Scientific and Technical Information of China (English)

    肖靖华; 刘升明; 田东波; 陈芸; 陈卫萍; 付志萍; 王海娥

    2016-01-01

    目的:探讨血清脑利钠肽(BNP)在慢性肺心病不同时期的诊断价值。方法选择符合入组标准的肺心病患者168例,按病情不同分为四组,分别为肺心病心功能代偿期组(B 组,n =43例)、肺心病右心衰竭组(C 组,n =45例)、单纯左心衰竭组(D 组,n =40例)、全心衰竭组(E 组,n =40例),另选择健康体检者为健康对照组(A 组,n =48例),检测各组血清 BNP 值、肺功能,进行心脏彩色多普勒超声检查,比较各组BNP 水平与各项指标的差异,并进行相关性分析;绘制各组 ROC 曲线,取最佳截点,分析 BNP 在慢性肺心病不同时期的诊断价值。结果A、B、C、D、E 组血清 BNP 值分别为(11.00±3.39)ng/L、(182.44±69.71)ng/L、(495.44±219.90)ng/L、(882.57±288.56)ng/L、(891.78±256.45)ng/L,五组差异有统计学意义(F =178.900,P =0.000);C 组血清 BNP 值高于 B 组(P <0.001);D 组、E 组血清 BNP 值均高于 C 组(P <0.001)。肺心病患者 BNP 与右心室舒张期内径(RV)、右心室流出道宽度(RVOT)、肺动脉压(PASP)呈正相关,与第1秒用力呼气量占预计值(FEV1%)呈负相关,与左心射血分数(LVEF%)无相关性;左心衰竭及全心衰竭患者,BNP 与 LVEF%呈负相关。肺心病心功能代偿期与肺心病右心衰竭患者的 BNP 最佳截点为285.3 ng/L,肺心病右心衰竭与全心衰竭患者的 BNP 最佳截点为764.2 ng/L。结论在慢性肺心病患者诊断中,血清BNP 水平与其病情进展有一定相关性,其动态监测对肺心病患者的判断有一定参考意义。%Objective To investigate the diagnostic value of serum brain natriuretic peptide(BNP)in chron-ic cor pulmonale of different period.Methods According to the inclusion criteria,we recruited 216 cases from heart and respiratory medicine

  3. Clinical analysis of treating acute decompensated heart failure by recombinant human brain natriuretic peptide and nitroglycerin%重组人脑利钠肽和硝酸甘油治疗急性失代偿性心力衰竭的临床分析

    Institute of Scientific and Technical Information of China (English)

    孙晶

    2015-01-01

    Objective: research clinical effects of treating acute decompensated heart failure by recombinant human brain natriuretic peptide and nitroglycerin. Method: choose 86 cases patients with acute or chronic heart failure received in our hospital, and randomly divided them into control and treatment group, 43 cases in each. Apply nitroglycerin for control group patients and recombinant human brain natriuretic peptide and nitroglycerin for treatment group. Compare patients of two groups before and after treatment with index of improvement magnitude of respiration and heart rate level, treatment effect of acute decompensated heart failure, number of adverse reactions during treatment, heart failure symptoms remission time, ECG recovery time to normal level, total time of heart disease medication therapy treatment. Result:improvement magnitude of respiration and heart rate level of treatment group patients is signiifcantly bettern than that of control group, difference is signiifcant between groups (P0.05);and heart failure symptoms remission time, ECG recovery time to normal level, total time of heart disease medication therapy treatment is obviously shorter than that of control group, difference between groups is signiifcant (P0.05);心衰症状缓解时间、心电图表现恢复正常时间、心衰疾病用药治疗总时间明显短于对照组,组间差异显著(P<0.05)。结论应用硝酸甘油与重组人脑利钠肽联合对患有急性失代偿性心力衰竭疾病的患者实施治疗的临床效果非常明显。

  4. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  5. Endomorphins and related opioid peptides.

    Science.gov (United States)

    Okada, Yoshio; Tsuda, Yuko; Bryant, Sharon D; Lazarus, Lawrence H

    2002-01-01

    Opioid peptides and their G-protein-coupled receptors (delta, kappa, mu) are located in the central nervous system and peripheral tissues. The opioid system has been studied to determine the intrinsic mechanism of modulation of pain and to develop uniquely effective pain-control substances with minimal abuse potential and side effects. Two types of endogenous opioid peptides exist, one containing Try-Gly-Gly-Phe as the message domain (enkephalins, endorphins, dynorphins) and the other containing the Tyr-Pro-Phe/Trp sequence (endomorphins-1 and -2). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2), which has high mu receptor affinity (Ki = 0.36 nM) and remarkable selectivity (4000- and 15,000-fold preference over the delta and kappa receptors, respectively), was isolated from bovine and human brain. In addition, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), isolated from the same sources, exhibited high mu receptor affinity (Ki = 0.69 nM) and very high selectivity (13,000- and 7500-fold preference relative to delta and kappa receptors, respectively). Both opioids bind to mu-opioid receptors, thereby activating G-proteins, resulting in regulation of gastrointestinal motility, manifestation of antinociception, and effects on the vascular systems and memory. To develop novel analgesics with less addictive properties, evaluation of the structure-activity relationships of the endomorphins led to the design of more potent and stable analgesics. Opioidmimetics and opioid peptides containing the amino acid sequence of the message domain of endomorphins, Tyr-Pro-Phe/Trp, could exhibit unique binding activity and lead to the development of new therapeutic drugs for controlling pain.

  6. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    of antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates. Areas covered: This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which...

  7. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.......Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  8. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  9. Bacteriocin Inducer Peptides

    Science.gov (United States)

    Novel peptides produced by bacteriocin-producing bacteria stimulate the production of bacteriocins in vitro. The producer bacteria are cultured in the presence of a novel inducer bacteria and a peptide having a carboxy terminal sequence of VKGLT in order to achieve an increase in bacteriocin produc...

  10. Avian host defense peptides

    NARCIS (Netherlands)

    Cuperus, Tryntsje; Coorens, M.; van Dijk, A.; Haagsman, H.P.

    2013-01-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense

  11. APD: the Antimicrobial Peptide Database

    OpenAIRE

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophob...

  12. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of the brain communicate and work with each other How changes in the brain ...

  13. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    Ravi Kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalography (EEG to determine whether specific information is stored in a subject's brain.

  14. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    ravi kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalograph y (EEG to determine whether specific information is stored in a subject's brain

  15. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  16. Long-term infusion of brain natriuretic peptide suppresses post myocardial infarction ventricular remodeling in rats%脑钠肽静脉滴注抑制大鼠心肌梗死后的心室重构

    Institute of Scientific and Technical Information of China (English)

    潘晔生; 魏盟; 朱伟; 马健; 辛平; 徐振兴; 韩蓓蓓; 何亚萍

    2011-01-01

    Objective To compare protective effects of chronic brain natriuretic peptide (BNP) infusion and enalapril administration on post myocardial infarction (MI) ventricular remodeling, and to investigate their effects on the matrix metalloproteinase(MMPs) expression in myocardium. Methods Rats were randomly assigned to sham-operated group, MI group in which MI models were prepared by coronary ligation, BNP group in which MI rats received chronic BNP infusion [0.06|ig/(kgmin)] and enalapril group in which MI rats received enalapril administration [10mg/(kgd)]. Ventricular remodeling and heart function were estimated by echocardiography (ECG), immunohistochemistry, ELISA and Western blot. Results Exogenous BNP infusion maintained a higher BNP level in heart tissue. BNP treatment achieved similar protective effects as enalapril therapy on postinfarction myocardial remodeling. Both BNP and enalapril inhibited the increase of left ventricular weight index by 13.2% and 16.9% respectively, (P <0.05). ECG results demonstrated that left ventricular end-diastolic diameter(LVEDD) and fractional shortening(FS) were more satisfactory in BNP and enalapril groups than in MI group [LVEDD: (8.8 ± 0.6)mm in MI group, (7.5 ± 0.7)mm in enalapril group, and (7.5 ± 1.0) mm in BNP group, P < 0.05; FS: (19.2 ± 2.6)% in MI group, (27.7 ± 5.6)% in enalapril group, and (27.5 ± 3.9) % in BNP group, P < 0.05]. Both enalapril and BNP inhibited collagen deposition in non-infarcted area obviously, especially type I collegen, by (6.8±1.4)% in MI group, (4.0±0.9)% in enalapril group, and (3.7±1.1)% in BNP group respectively(P < 0.05). BNP infusion increased cyclic guanosine monophosphate (cGMP) concentration in cardiac tissue more significantly than enalapril, while inhibited angiotensin Ⅱ less significantly than enalapril. BNP infusion did not lead to obvious change of MMP-2 and MMP-9 content in non-infarcted area. Conclusion Continuous BNP infusion may play cardiac protection roles through

  17. Central and Peripheral Significance of Neuropeptide Y and Its Related Peptides

    Science.gov (United States)

    1990-11-15

    Neuropeptide Y-Like Immunoreactive Peptides in the Nervous System and Midgut of Locusta migratoria and in the Brain of Sarcophaga bullata. By LILIANE...Characterization of Neuropeptide Y-Like Immunoreactive Peptides in the Nervous System and Midgut of Locusta migratoria and in the Brain of Sarcophaga bullata...neuropeptide tyrosine) in two insect species, Locusta migratoria and Sarcophaga bullata. NPY has a widespread distribution and is present in extremely high

  18. Brain components

    Science.gov (United States)

    ... can make complex movements without thinking. The brain stem connects the brain with the spinal cord and is composed of ... structures: the midbrain, pons, and medulla oblongata. The brain stem provides us with automatic functions that are necessary ...

  19. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  20. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  2. Brain Basics

    Medline Plus

    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  3. 可卡因-苯丙胺调节转录肽在脑缺血中的神经保护机制%Neuroprotective mechanisms of cocaine-and amphetamine-regulated transcript peptides in brain ischemia

    Institute of Scientific and Technical Information of China (English)

    王路娜; 沙杜鹃; 张均

    2013-01-01

    可卡因-苯丙胺调节转录肽(cocaine-and amphetamine-regulated transcript peptides,CART)是一种存在于人和动物的内源性神经肽,参与调节体内多种生理和病理学过程.多项研究提示,CART在中枢神经系统中广泛分布,具有一定的中枢神经保护作用.文章对CART在脑缺血中的神经保护机制进行了综述.%Cocaine-and amphetamine-regulated transcript(CART) peptides are endogenous neurotransmitters with important roles in a number of physiological and pathological processes in vivo.Many studies suggested that CART is widely distributed in the central nervous system,and it has some central protective effects.This article reviews the recent progress in research on the protective effect of CART on cerebral ischemia and its mechanisms.

  4. Anti-antimicrobial Peptides

    Science.gov (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  5. Reference range of plasma N-terminal pro-brain natriuretic peptide levels in early preterm infants%早期早产儿血浆N末端脑钠肽参考值范围

    Institute of Scientific and Technical Information of China (English)

    张茜; 罗成汉; 时赞扬; 卢洁; 程欣茹; 徐千雅; 郭宏湘; 王丽; 程秀永

    2013-01-01

    .358,t1d与7 d=14.743,t3d与7d =11.105,P均=0.000).出生后1d、3d、7d早产儿血浆NT-proBNP水平分别为(1875 ±686) ng/L、(1615±574) ng/L、(1118 ±380) ng/L;均数95%置信区间分别为530~3220 ng/L、490~2740 ng/L、373~ 1863 ng/L.结论 早产儿血浆NT-proBNP水平出生第1天达高峰,之后随日龄增加而下降,二者呈负相关;血浆NT-proBNP水平不受胎龄、性别、出生体质量、分娩方式及营养方式的影响.%Objective To establish the reference range of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in early preterm infants.Methods 1.Inclusion criteria of the subjects:(1) preterm infants admitted to Neonatal Ward of First Affiliated Hospital of Zhengzhou University between Oct.2009 and Aug.2012 within 24 hours after birth;(2) maternal health during pregnancy; (3) written informed consent obtained from parents;(4) normal laboratory examination results such as blood gas analysis,electrolyte,hepatorenal function,myocardial enzyme,routine blood count and infectious disease screening (hepatitis B,hepatitis C,syphilis and acquired immune deficiency syndrome) within 24 hours after birth.Plasma NT-proBNP levels were measured on day 1,day 3 and day 7 of life.Variable data was analyzed using the Shapiro-Wilk test for normality test.Difference in plasma NT-proBNP levels on different days of life was analyzed using repeated measure analysis of variance.A multiple regression analysis was performed to determine the influencing factors for plasma NT-proBNP level,reference value interval:reference range containing 95 % of the reference population,namely(x-1.96 s)-(x-+ 1.96 s),with inspection level α =0.05.Results 1.A total of 204 preterm infants (104 cases were male and 100 cases were female) were included in the present study,with gestational age ranging from 27 + 1 to 36 +6 weeks(median 33 weeks) and birth weight ranging from 700 to 3050 g (median 1590 g).Of these preterm infants,vaginal delivery were 78

  6. 严重延迟复苏烧伤休克患者血浆脑钠肽的变化%Change in plasma brain natriuretic peptide and its clinical significance in burn patients after delayed fluid resuscitation of shock

    Institute of Scientific and Technical Information of China (English)

    黄永新; 詹新华; 郑静伟; 吴祖煌; 陈建崇; 朱剑仙; 谢包根; 刘世康

    2010-01-01

    Objective To observe the early change in plasma brain natriuretic peptide (BNP) level in burn patients with long delayed fluid resuscitation of burn shock and its clinical significance.Methods Thirty-six burn patients with second and third degree of burn covering 32%- 92% total body surface area were enrolled for the study, among them 10 patients were complicated with serious heart failure (heart failure group), and 26 patients rallied from shock after delayed fluid resuscitation without heart failure (stable group).The level of plasma BNP, lactate dehydrogenase (LDH), MB isoenzyme of creatine kinase (CK-MB), and left ventricle ejection fraction (LVEF) were determined at admission and 3 hours after hospitalization, and 24, 48, 72, 168 hours after the injury in both groups with electrochemiluminescence (ECL).Results Compared with stable group, the plasma BNP level (ng/L) of heart failure group at 3 hours after hospitalization, and 24, 48, 72 hours after the burn injury increased significantly (3 hours after hospitalization: 1 521.38±121.11 vs.391.36±63.27, 24 hours after burn: 2 516.86±193.25 vs.360.79±146.56, 48 hours after burn: 1 587.76±169.23 vs.398.92±77.46, 72 hours after burn: 974.45±166.33vs.283.43 ± 68.15, all P< 0.01), the level of LVEF lowered significantly (3 hours after hospitalization;0.33±0.03 vs.0.58±0.09, 24 hours after burn: 0.36±0.09 vs.0.60±0.10, 48 hours after burn: 0.35±0.08 vs.0.62±0.11, 72 hours after burn: 0.39±0.10 vs.0.64±0.10, all P<0.05).The levels of LDH (μmol·s-1·L-1)in stable group were 2.87±0.50 at admission,3.02±0.43 3hours after hospitalization,4.02±0.87 24 hours after burn, 6.90±0.87 48 hours after burn, 3.64±0.75 72 hours after burn, 2.670.45 168 hours after burn while in heart failure group, they were 2.97±1.40, 3.84±0.37, 4.29±0.45,8.50±0.38, 3.84±0.62, 2.30±0.38, respectively;and CK-MB (U/L) in stable group were 59.12±13.75at admission, 70.39 ±10.72 3 hours after hospitalization, 79.29 ±17

  7. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  8. Immunotherapy with Allergen Peptides

    OpenAIRE

    Larché Mark

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cro...

  9. Antimicrobial Peptides in Echinoderms

    OpenAIRE

    Li, C; Haug, T; K Stensvåg

    2010-01-01

    Antimicrobial peptides (AMPs) are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, d...

  10. Anatomy of the Brain

    Science.gov (United States)

    ... Menu Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ... form Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ...

  11. Clinical observation of lyophilized recombinant human brain natriuretic peptide for the treatment of acute decompensated heart failure%冻干重组人脑利钠肽治疗急性失代偿性心力衰竭临床观察

    Institute of Scientific and Technical Information of China (English)

    王沐; 魏盟

    2014-01-01

    目的:研究冻干重组人脑利钠肽治疗急性代偿性心力衰竭的临床效果。方法选择急性失代偿性心力衰竭患者90例,随机分成观察组(45例)和对照组(45例)。对2组患者均进行常规治疗,观察组同时静脉注射冻干重组人脑利钠肽;对照组则静脉注射硝酸甘油。结果治疗前观察组和对照组左心室舒张末期内径(LVEDD)及左心室射血分数(LVEF)差异无统计学意义(P>0.05)。治疗后观察组LVEDD显著小于对照组(P<0.01),LVEF显著高于对照组(P<0.01)。治疗前2组患者动脉血二氧化碳分压(PaCO2)、时间肺活量、收缩压及动脉血氧饱和度比较差异均无统计学意义(P>0.05)。治疗后观察组PaCO2、收缩压显著低于对照组(P<0.01),时间肺活量和动脉血氧饱和度显著高于对照组(P<0.01)。结论冻干重组人脑利钠肽可以有效改善急性失代偿性心力衰竭患者的心脏功能以及呼吸功能。%Objective To study the clinical effect of lyophilized recombinant human brain natriuretic peptide for the treatment of acute decompensated heart failure .Methods 90 patients with acute decompensated heart failure were ran-domly divided into observation group (n=45) and control group (n=45).The patients in both groups received routine treatment .The patients in the observation group received lyophilized recombinant human brain natriuretic peptide intrave -nous injection .The patients in the control group received intravenous injection of nitroglycerin .Results Before treat-ment, the left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) between the two groups showed no statistical difference (P>0.05).After treatment, the LVEDD in the observation group were signifi-cantly less than that in the control group (P0.05).After treatment, the PaCO2 and systolic blood pressure were significantly lower in the

  12. 重组人脑钠肽对心肌梗死所致急性心力衰竭的疗效和肾功能的影响%Effect of recombinant human brain natriuretic peptide on the efficacy and renal function of acute heart failure caused by myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    杨光

    2015-01-01

    目的:分析和探讨重组人脑钠肽对心肌梗死所致急性心力衰竭的疗效和肾功能的影响。方法选择在漯河市中心医院进行治疗的心肌梗死所致急性心力衰竭患者60例,随机将其分为观察组和对照组,每组30例,对照组给予常规、纠正心力衰竭以及硝酸甘油治疗,观察组则在常规治疗和纠正心力衰竭治疗的基础上给予重组人脑利钠肽(rhBNP)注射治疗,治疗结束后对两组患者的心功能指标、心力衰竭症状缓解情况进行比较,并检测血浆脑钠肽、尿素氮、血肌酐浓度和24 h 尿量。结果观察组和对照组治疗总有效率分别为96.7%和73.3%,观察组显著高于对照组,差异有统计学意义(P 0.05)。结论心肌梗死所致急性心力衰竭采用重组人脑钠肽进行治疗能够有效提高疗效,并且不会影响患者的肾功能,建议在临床上推广应用。%Objective To analyze and investigate the effect of recombinant human brain natriuretic peptide on the efficacy and renal function of acute heart failure caused by myocardial infarction. Methods Sixty patients with acute heart failure caused by myocardial infarction in the central hospital of Luohe were selected and divided into the observation group and the control group,with 30 cases in each group. The patients in the control group were given routine treatment, correcting heart failure treatment and nitroglycerin treatment; and the patients in the observation group were given rhBNP injection in addition. Heart function indexes and remission of the symptoms of heart failure of two groups were compared after treat-ment, plasma brain natriuretic peptide,urea nitrogen, concentration of serum creatinine,24 h urinary volume were checked. Results In the observation group and the control group, the total effective rate was 96. 7% and 73. 3% , that in the observation group was significantly higher than that in the control group(P 0. 05

  13. CART peptide induces neuroregeneration in stroke rats.

    Science.gov (United States)

    Luo, Yu; Shen, Hui; Liu, Hua-Shan; Yu, Seong-Jin; Reiner, David J; Harvey, Brandon K; Hoffer, Barry J; Yang, Yihong; Wang, Yun

    2013-02-01

    Utilizing a classic stroke model in rodents, middle cerebral artery occlusion (MCAo), we describe a novel neuroregenerative approach using the repeated intranasal administration of cocaine- and amphetamine-regulated transcript (CART) peptide starting from day 3 poststroke for enhancing the functional recovery of injured brain. Adult rats were separated into two groups with similar infarction sizes, measured by magnetic resonance imaging on day 2 after MCAo, and were treated with CART or vehicle. The CART treatment increased CART level in the brain, improved behavioral recovery, and reduced neurological scores. In the subventricular zone (SVZ), CART enhanced immunolabeling of bromodeoxyuridine, a neural progenitor cell marker Musashi-1, and the proliferating cell nuclear antigen, as well as upregulated brain-derived neurotrophic factor (BDNF) mRNA. AAV-GFP was locally applied to the SVZ to examine migration of SVZ cells. The CART enhanced migration of GFP(+) cells from SVZ toward the ischemic cortex. In SVZ culture, CART increased the size of neurospheres. The CART-mediated cell migration from SVZ explants was reduced by anti-BDNF blocking antibody. Using (1)H-MRS (proton magnetic resonance spectroscopy), increases in N-acetylaspartate levels were found in the lesioned cortex after CART treatment in stroke brain. Cocaine- and amphetamine-regulated transcript increased the expression of GAP43 and fluoro-ruby fluorescence in the lesioned cortex. In conclusion, our data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain.

  14. Small molecule inhibitors of amyloid β peptide aggregation as a potential therapeutic strategy for Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Qin NIE; Xiao-guang DU; Mei-yu GENG

    2011-01-01

    Amyloid β (Aβ) peptides have long been viewed as a potential target for Alzheimer's disease (AD). Aggregation of Aβ peptides in the brain tissue is believed to be an exclusively pathological process. Therefore, blocking the initial stages of Aβ peptide aggregation with small molecules could hold considerable promise as the starting point for the development of new therapies for AD. Recent rapid progresses in our understanding of toxic amyloid assembly provide a fresh impetus for this interesting approach. Here, we discuss the problems, challenges and new concepts in targeting Aβ peptides.

  15. Changes in Serum Natriuretic Peptide Levels after Percutaneous Closure of Small to Moderate Ventricular Septal Defects

    Directory of Open Access Journals (Sweden)

    Yuksel Kaya

    2012-01-01

    Full Text Available Background. B-type natriuretic peptide has been shown to be a very sensitive and specific marker of heart failure. In this study, we aimed to investigate the effect of percutaneous closure of ventricular septal defects with Amplatzer septal occluders on brain natriuretic peptide levels. Methods. Between 2008 and 2011, 23 patients underwent successfully percutaneous ventricular septal defect closure in 4 cardiology centers. Brain natriuretic peptide levels were measured in nine patients (4 male, mean ages were 25.3±14.3 who underwent percutaneous closure with Amplatzer occluders for membranous or muscular ventricular septal defects were enrolled in the study. Brain natriuretic peptide levels were measured one day before and one month after the closure. Patients were evaluated clinically and by echocardiography one month after the procedure. Results. Percutaneous closures of ventricular septal defects were successfully performed in all patients. There was not any significant adverse event in patients group during followup. Decrease in brain natriuretic peptide levels after closure were statistically significant (97.3±78.6 versus 26.8±15.6, =0.013. Conclusion. Brain Natriuretic Peptide levels are elevated in patients with ventricular septal defects as compared to controls. Percutaneous closure of Ventricular Septal Defect with Amplatzer occluders decreases the BNP levels.

  16. Correlated Inflammatory Responses and Neurodegeneration in Peptide-Injected Animal Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    James G. McLarnon

    2014-01-01

    Full Text Available Animal models of Alzheimer’s disease (AD which emphasize activation of microglia may have particular utility in correlating proinflammatory activity with neurodegeneration. This paper reviews injection of amyloid-β (Aβ into rat brain as an alternative AD animal model to the use of transgenic animals. In particular, intrahippocampal injection of Aβ1-42 peptide demonstrates prominent microglial mobilization and activation accompanied by a significant loss of granule cell neurons. Furthermore, pharmacological inhibition of inflammatory reactivity is demonstrated by a broad spectrum of drugs with a common endpoint in conferring neuroprotection in peptide-injected animals. Peptide-injection models provide a focus on glial cell responses to direct peptide injection in rat brain and offer advantages in the study of the mechanisms underlying neuroinflammation in AD brain.

  17. Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent

    Science.gov (United States)

    Liu, Lihong; Xu, Kaijin; Wang, Huaying; Jeremy Tan, P. K.; Fan, Weimin; Venkatraman, Subbu S.; Li, Lanjuan; Yang, Yi-Yan

    2009-07-01

    Antimicrobial cationic peptides are of interest because they can combat multi-drug-resistant microbes. Most peptides form α-helices or β-sheet-like structures that can insert into and subsequently disintegrate negatively charged bacterial cell surfaces. Here, we show that a novel class of core-shell nanoparticles formed by self-assembly of an amphiphilic peptide have strong antimicrobial properties against a range of bacteria, yeasts and fungi. The nanoparticles show a high therapeutic index against Staphylococcus aureus infection in mice and are more potent than their unassembled peptide counterparts. Using Staphylococcus aureus-infected meningitis rabbits, we show that the nanoparticles can cross the blood-brain barrier and suppress bacterial growth in infected brains. Taken together, these nanoparticles are promising antimicrobial agents that can be used to treat brain infections and other infectious diseases.

  18. Diversity-Oriented Peptide Stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged...... as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...... incorporating two azide-modified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and (i, i+9)-stapled peptides with a single free alkyne positioned on the staple, that can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access...

  19. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  20. Changes of.serum high mobility group box-1 and epithelial neutrophil-activing peptide-78 in patients with acute brain injury%急性颅脑损伤后血高迁移率蛋白-1及中性粒细胞激活肽-78的变化

    Institute of Scientific and Technical Information of China (English)

    李曙晨; 黄友敏

    2011-01-01

    Objective To investigate the dynamic changes of serum high mobility group box-1 (HMGB1)and epithelial neutrophil-activing peptide-78(ENA-78)associated with secondary brain edema in patients following acute brain injury.Methods The serum HMGB1 and ENA-78 in 110 patients with acute brain injury were determined by using enzyme-linked immunosorbent assay(ELISA)12 hours,3 days and the 5 days after acute brain injury.The outcomes were analyzed by t-test and estimated well with clinical symptoms,imaging data and Glasgow Outcome Scale(GOS)in combination of.Results The levels of HMGB1 and ENA-78 increased significantly with lowering the score of GCS 12 hours after acute brain injury.The more severity of acute brain injury resulted in more production of HMGB1 and ENA-78 and longer period of persisted and peaked brain edema(all P <0.01).HMGB1 levels had positive correlation with severity and persistence of brain edema(r =0.69,P <0.01 and r =0.70,P <0.01).ENA-78 levels had positive correlation with severity and persistence of brain edema(r =0.62,P < 0.01 and r =0.65,P < 0.01).Furthermore,there were statistical differences in HMGB1 and ENA-78 levels between different GOS groups.Compared with good outcome group and normal control group,the HMGB1 and ENA-78 levels in poor outcome group persistently increased and were higher within 5 days after brain injury(P < 0.01 or P <0.05).There was a correlation between serum HMGB1 and ENA-78 levels in patients with acute brain injuries(r =0.68,P < 0.01).Conclusions The changes of serum HMGB1 and ENA-78 levels were closely associated with secondary brain edema in patients following acute brain injury.%目的 研究急性颅脑损伤后血中高迁移率蛋白-1(HMGB1)和中性粒细胞激活肽-78(ENA-78)的动态变化及其与继发性脑水肿的关系.方法 采用酶联免疫吸附法(ELISA)检测HMGB1和ENA-78血中含量,回顾性分析110例急性颅脑损伤住院患者伤后12 h内、伤后第3,5d血中HMGB1

  1. Insights into the molecular interactions between aminopeptidase and amyloid beta peptide using molecular modeling techniques.

    Science.gov (United States)

    Dhanavade, Maruti J; Sonawane, Kailas D

    2014-08-01

    Amyloid beta (Aβ) peptides play a central role in the pathogenesis of Alzheimer's disease. The accumulation of Aβ peptides in AD brain was caused due to overproduction or insufficient clearance and defects in the proteolytic degradation of Aβ peptides. Hence, Aβ peptide degradation could be a promising therapeutic approach in AD treatment. Recent experimental report suggests that aminopeptidase from Streptomyces griseus KK565 (SGAK) can degrade Aβ peptides but the interactive residues are yet to be known in detail at the atomic level. Hence, we developed the three-dimensional model of aminopeptidase (SGAK) using SWISS-MODEL, Geno3D and MODELLER. Model built by MODELLER was used for further studies. Molecular docking was performed between aminopeptidase (SGAK) with wild-type and mutated Aβ peptides. The docked complex of aminopeptidase (SGAK) and wild-type Aβ peptide (1IYT.pdb) shows more stability than the other complexes. Molecular docking and MD simulation results revealed that the residues His93, Asp105, Glu139, Glu140, Asp168 and His255 are involved in the hydrogen bonding with Aβ peptide and zinc ions. The interactions between carboxyl oxygen atoms of Glu139 of aminopeptidase (SGAK) with water molecule suggest that the Glu139 may be involved in the nucleophilic attack on Ala2-Glu3 peptide bond of Aβ peptide. Hence, amino acid Glu139 of aminopeptidase (SGAK) might play an important role to degrade Aβ peptides, a causative agent of Alzheimer's disease.

  2. Broad characterization of endogenous peptides in the tree shrew visual system.

    Science.gov (United States)

    Ranc, Vaclav; Petruzziello, Filomena; Kretz, Robert; Argandoña, Enrike G; Zhang, Xiaozhe; Rainer, Gregor

    2012-05-17

    Endogenous neuropeptides, acting as neurotransmitters or hormones in the brain, carry out important functions including neural plasticity, metabolism and angiogenesis. Previous neuropeptide studies have focused on peptide-rich brain regions such as the striatum or hypothalamus. Here we present an investigation of peptides in the visual system, composed of brain regions that are generally less rich in peptides, with the aim of providing the first broad overview of peptides involved in mammalian visual functions. We target three important parts of the visual system: the primary visual cortex (V1), lateral geniculate nucleus (LGN) and superior colliculus (SC). Our study is performed in the tree shrew, a close relative of primates. Using a combination of data dependent acquisition and targeted LC-MS/MS based neuropeptidomics; we identified a total of 52 peptides from the tree shrew visual system. A total of 26 peptides, for example GAV and neuropeptide K were identified in the visual system for the first time. Out of the total 52 peptides, 27 peptides with high signal-to-noise-ratio (>10) in extracted ion chromatograms (EIC) were subjected to label-free quantitation. We observed generally lower abundance of peptides in the LGN compared to V1 and SC. Consistently, a number of individual peptides showed high abundance in V1 (such as neuropeptide Y or somatostatin 28) and in SC (such as somatostatin 28 AA1-12). This study provides the first in-depth characterization of peptides in the mammalian visual system. These findings now permit the investigation of neuropeptide-regulated mechanisms of visual perception.

  3. Angiotensin peptides and central autonomic regulation.

    Science.gov (United States)

    Diz, Debra I; Arnold, Amy C; Nautiyal, Manisha; Isa, Katsunori; Shaltout, Hossam A; Tallant, E Ann

    2011-04-01

    Aging, hypertension, and fetal-programmed cardiovascular disease are associated with a functional deficiency of angiotensin (Ang)-(1-7) in the brain dorsomedial medulla. The resulting unrestrained activity of Ang II in brainstem regions negatively impacts resting mean arterial pressure, sympathovagal balance, and baroreflex sensitivity for control of heart rate. The differential effects of Ang II and Ang-(1-7) may be related to the cellular sources of these peptides as well as different precursor pathways. Long-term alterations of the brain renin-angiotensin system may influence signaling pathways including phosphoinositol-3-kinase and mitogen-activated protein kinase and their downstream mediators, and as a consequence may influence metabolic function. Differential regulation of signaling pathways in aging and hypertension by Ang II versus Ang-(1-7) may contribute to the autonomic dysfunction accompanying these states.

  4. Immunotherapy with Allergen Peptides

    Directory of Open Access Journals (Sweden)

    Larché Mark

    2007-06-01

    Full Text Available Specific allergen immunotherapy (SIT is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.

  5. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  6. β-PEPTIDES CYCLOBUTANIQUES

    OpenAIRE

    Fernandez, Carlos

    2008-01-01

    The synthesis of β-amino acids, structural analogues of?-Amino acids, is an issue essential in the development of oligopeptides. A lot of work has been conducted on the behavior of β-peptide (sequence of β-amino acids) as well as peptides mixed (mixed β-and β- amino acids). As a result, the conformational preference of β-amino acids will induce the appearance of a three-dimensional structure of the oligopeptide ordered. Thus, several types of helices, sheets and elbows were observed in β-olig...

  7. Invertebrate FMRFamide related peptides.

    Science.gov (United States)

    Krajniak, Kevin G

    2013-06-01

    In 1977 the neuropeptide FMRFamide was isolated from the clam, Macrocallista nimbosa. Since then several hundred FMRFamide-related peptides (FaRPs) have been isolated from invertebrate animals. Precursors to the FaRPs likely arose in the cnidarians. With the transition to a bilateral body plan FaRPs became a fixture in the invertebrate phyla. They have come to play a critical role as neurotransmitters, neuromodulators, and neurohormones. FaRPs regulate a variety of body functions including, feeding, digestion, circulation, reproduction, movement. The evolution of the molecular form and function of these omnipresent peptides will be considered.

  8. Dicyclopropylmethyl peptide backbone protectant.

    Science.gov (United States)

    Carpino, Louis A; Nasr, Khaled; Abdel-Maksoud, Adel Ali; El-Faham, Ayman; Ionescu, Dumitru; Henklein, Peter; Wenschuh, Holger; Beyermann, Michael; Krause, Eberhard; Bienert, Michael

    2009-08-20

    The N-dicyclopropylmethyl (Dcpm) residue, introduced into amino acids via reaction of dicyclopropylmethanimine hydrochloride with an amino acid ester followed by sodium cyanoborohydride or triacetoxyborohydride reduction, can be used as an amide bond protectant for peptide synthesis. Examples which demonstrate the amelioration of aggregation effects include syntheses of the alanine decapeptide and the prion peptide (106-126). Avoidance of cyclization to the aminosuccinimide followed substitution of Fmoc-(Dcpm)Gly-OH for Fmoc-Gly-OH in the assembly of sequences containing the sensitive Asp-Gly unit.

  9. Progress in the Predictive Value of Brain Natriuretic Peptide for Congestive Heart Failure%脑钠肽对充血性心力衰竭近期预后影响研究进展

    Institute of Scientific and Technical Information of China (English)

    洪斌; 葛均波

    2007-01-01

    脑钠肽(brain natriuretic peptide,BNP)是由心室分泌的一种调节心血管系统功能的多肽类激素,半衰期为23min,随充血性心力衰竭(congestive heart failure,CHF)的加重而分泌增加。BNP来源于心室,心肌缺血、损伤、坏死,心室壁张力和压力过重、苯福林、肾上腺素、异丙肾上腺素等均刺激BNP的合成与分泌。BNP通过受体起作用。

  10. Amyloid-β(25-35) peptides aggregate into cross-β sheets in unsaturated anionic lipid membranes at high peptide concentrations.

    Science.gov (United States)

    Tang, Jennifer; Alsop, Richard J; Backholm, Matilda; Dies, Hannah; Shi, An-Chang; Rheinstädter, Maikel C

    2016-04-07

    One of the hallmarks of Alzheimer's disease is the formation of protein plaques in the brain, which mainly consist of amyloid-β peptides of different lengths. While the role of these plaques in the pathology of the disease is not clear, the mechanism behind peptide aggregation is a topic of intense research and discussion. Because of their simplicity, synthetic membranes are promising model systems to identify the elementary processes involved. We prepared unsaturated zwitterionic/anionic lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-phosphocholine (POPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine (DMPS) at concentrations of POPC/3 mol% DMPS containing 0 mol%, 3 mol%, 10 mol%, and 20 mol% amyloid-β25-35 peptides. Membrane-embedded peptide clusters were observed at peptide concentrations of 10 and 20 mol% with a typical cluster size of ∼11 μm. Cluster density increased with peptide concentration from 59 (±3) clusters per mm(2) to 920 (±64) clusters per mm(2), respectively. While monomeric peptides take an α-helical state when embedded in lipid bilayers at low peptide concentrations, the peptides in peptide clusters were found to form cross-β sheets and showed the characteristic pattern in X-ray experiments. The presence of the peptides was accompanied by an elastic distortion of the bilayers, which can induce a long range interaction between the peptides. The experimentally observed cluster patterns agree well with Monte Carlo simulations of long-range interacting peptides. This interaction may be the fundamental process behind cross-β sheet formation in membranes and these sheets may serve as seeds for further growth into amyloid fibrils.

  11. The Plasma Levels of Brain Natriuretic Peptide (BNP) in Patients With Acute Myocardial Infarction (AMI) Study of the Change%血浆中脑钠素(BNP)在急性心肌梗死(AMI)后的水平变化研究

    Institute of Scientific and Technical Information of China (English)

    祝红娟

    2015-01-01

    ObjectiveTo study the plasma levels of brain natriuretic peptide (BNP) in patients with acute myocardial infarction (AMI) after the change level.Methods the changes of BNP between the two groups comparison between AMI patients and healthy people.Results The observation group patients with 24 h within the plasma levels of BNP was significantly increased compared to the same period, with statistically significant difference between groups (P<0.05). ConclusionThe level of serum BNP in patients with acute myocardial infarction value to make early diagnosis of myocardial infarction with positive value.%目的:研究血浆中脑钠素(BNP)在急性心肌梗死(AMI)后的水平变化情况。方法对比 AMI患者和健康人两组间BNP变化。结果观察组患者24 h之内的BNP血浆水平明显增高,组间差异具有统计学意义(P<0.05)。结论急性心肌梗死患者的血浆BNP值对心肌梗死作出早期诊断具有积极的价值。

  12. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure

    DEFF Research Database (Denmark)

    Halbirk, Mads; Nørrelund, Helene; Møller, Niels

    2010-01-01

    )) and placebo infusion. At 0 and 48 h, LVEF, diastolic function, tissue Doppler regional myocardial function, exercise testing, noninvasive cardiac output, and brain natriuretic peptide (BNP) were measured. Blood pressure, heart rate, and metabolic parameters were recorded. Fifteen patients completed...

  13. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  14. Brain Basics

    Medline Plus

    Full Text Available ... depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of ... but sometimes give rise to disabilities or diseases. neural circuit —A network of neurons and their interconnections. ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ... depression experience when starting treatment. Gene Studies Advanced technologies are also making it faster, easier, and more ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... blues" from time to time. In contrast, major depression is a serious disorder that lasts for weeks. ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... the brain cannot effectively coordinate the billions of cells in the body, the results can affect many ... unit of the brain and nervous system. These cells are highly specialized for the function of conducting ...

  18. Brain Diseases

    Science.gov (United States)

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... related to changes in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot ... their final destination. Chemical signals from other cells guide neurons in forming various brain structures. Neighboring neurons ...

  20. Brain Basics

    Medline Plus

    Full Text Available ... in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... the basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

  2. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    . An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  3. C-peptide and Diabetic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Xiao-jun Cai; Hui-qin Xu; Yi Lu

    2011-01-01

    With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive fimctions.Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system,hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide defidency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients.Those Findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.

  4. Brain Basics

    Medline Plus

    Full Text Available ... such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit ... final destination. Chemical signals from other cells guide neurons in forming various brain structures. Neighboring neurons make connections with each other ...

  5. Brain Aneurysm

    Science.gov (United States)

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  6. The Brain.

    Science.gov (United States)

    Hubel, David H.

    1979-01-01

    This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

  7. Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger;

    2011-01-01

    The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...... that preeclampsia is associated with cardiovascular changes in early pregnancy....

  8. Peptide vectors for gene delivery: from single peptides to multifunctional peptide nanocarriers.

    Science.gov (United States)

    Raad, Markus de; Teunissen, Erik A; Mastrobattista, Enrico

    2014-07-01

    The therapeutic use of nucleic acids relies on the availability of sophisticated delivery systems for targeted and intracellular delivery of these molecules. Such a gene delivery should possess essential characteristics to overcome several extracellular and intracellular barriers. Peptides offer an attractive platform for nonviral gene delivery, as several functional peptide classes exist capable of overcoming these barriers. However, none of these functional peptide classes contain all the essential characteristics required to overcome all of the barriers associated with successful gene delivery. Combining functional peptides into multifunctional peptide vectors will be pivotal for improving peptide-based gene delivery systems. By using combinatorial strategies and high-throughput screening, the identification of multifunctional peptide vectors will accelerate the optimization of peptide-based gene delivery systems.

  9. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  10. 生物标志物-血清脑钠素在充血性心力衰竭诊断中的价值%Measurement of Serum Brain Natriuretic Peptide Level as a Biomarker for Congestive Heart Failure

    Institute of Scientific and Technical Information of China (English)

    王频佳; 王娴

    2007-01-01

    Objective To explore the value of Brain Natriuretic pepfide (BNP) in estimating the degree of seriousness of congestive heart failure (HF) and study BNP level of CHF caused by various cardiovascular diseases.Methods 100 patients with CHF were divided into three classes (classⅠ,Ⅱ and Ⅳ)by New York Heart Association (NYHA) functional classification Standard. 100 healthy individuals were selected into control group.Serum BNP concentration Were measured by electrochemical luminescence assay (Elecsys 2010,Roche Diagnostics).Results Mean serum BNP concentration of patients with CHF was 4 745.49±3 698.70 ng/ml,which was higher significantly than that of normal control (66.18±44.30ng/ml).Moreover,the growth in BNP level was increased with NYHA functional classification:class Ⅳ (1 0251±9 326.8 ng/ml) >class Ⅲ(1 239±1 063.8 ng/ml) > class Ⅱ (167.4±143.4 ng/ml),which was statistically significant (P0.05),但NYHAⅡ级各病因组间BNP水平差异有显著性(P<0.05).结论 CHF患者血清BNP水平显著增高,且随着NYHA分级增加而增加,可作为评价CHF严重程度的客观指标.

  11. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

  12. APD: the Antimicrobial Peptide Database.

    Science.gov (United States)

    Wang, Zhe; Wang, Guangshun

    2004-01-01

    An antimicrobial peptide database (APD) has been established based on an extensive literature search. It contains detailed information for 525 peptides (498 antibacterial, 155 antifungal, 28 antiviral and 18 antitumor). APD provides interactive interfaces for peptide query, prediction and design. It also provides statistical data for a select group of or all the peptides in the database. Peptide information can be searched using keywords such as peptide name, ID, length, net charge, hydrophobic percentage, key residue, unique sequence motif, structure and activity. APD is a useful tool for studying the structure-function relationship of antimicrobial peptides. The database can be accessed via a web-based browser at the URL: http://aps.unmc.edu/AP/main.html.

  13. Protective effect of cocaine-and amphetamine-regulated transcript peptide in ischemic brain injury%可卡因-苯丙胺调节转录肽在缺血性脑损伤中的保护作用

    Institute of Scientific and Technical Information of China (English)

    金佳丽; 徐运

    2010-01-01

    可卡因-苯丙胺调节转录肽(cocaine-and amphetamine-regulated transcript,CART)是一种内源性神经肽,广泛分布于脑、胃肠道和胰腺等器官组织,具有多种重要的生理功能,包括进食与肥胖、应激、精神焦虑行为、药物成瘾和内分泌调节等.前期研究提示,CART在中枢神经系统广泛分布,并且参与调节多种生理学过程,具有一定的中枢保护作用,是一种很有潜力的神经保护剂.文章就CART对卒中以及神经变性疾病的神经保护作用及其机制,以及其在中枢神经系统疾病治疗作用等方面的研究进展进行了综述.%Cocaine-and amphetamine-regulated transcript (CART), an endogenous neuropeptide, is widely distributed in human organs and tissues, such as brain, gastrointestinal tract and pancreas. It has a variety of important physiological functions, including eating and obesity, stress, mental anxiety, drug addition, and endocrine regulation. Previous studies have suggested that CART is widely distributed in the central nervous system, and it involves in the regulation of a variety of physiological processes and has some central protective effects. It is a potential neuroprotective agent. This article reviews the recent progress in research on the neuroprotective effect of CART on stroke and neurodegenerative disease and its mechanisms, as well as its therapeutic effect in central nervous system diseases.

  14. [Amphibian skin as a source of therapeutic peptides].

    Science.gov (United States)

    Amiche, Mohamed

    2016-01-01

    The search for new bioactive molecules that could be used in therapeutics is a major public health issue, particularly in the treatment of certain diseases such as cancer. In this context the exploration of the venom of animals (snakes, amphibians, cones, scorpions, insects...) that produce molecules of various structures and biological activities, is a very promising direction. Research in this area led to the discovery of neuropeptides, hormones, toxins, antimicrobial peptides and other extremely potent mediators. These are now used in many areas both in fundamental research and in translational research, respectively, to understand biochemical and physiological mechanisms, or to use as medical diagnostic tools and for therapeutic purposes. Pr. V. Erspamer is the first researcher to have shown, in the 1930s, that in addition to biogenic amines and alkaloids, granular glands from the skin of amphibians also produced huge amounts of peptides with various structures and biological activities. He also showed that these peptides had their counterparts, most often in the form of identical or similar peptides, in the central nervous system and the gastrointestinal tract of mammals. These observations are summarized in the form of a triangle concept of "brain-gut-skin" that states that any peptide found in a compartment should be present in the other two. In addition, abundance, ease of extraction and identification of peptides from amphibian skin make this model a means to search for their counterparts in mammals where they are present in minute quantities. This approach has two advantages: (i) at the fundamental level, the large peptide diversity, ubiquity and multiplicity of functions to which they participate, constitute a true chemical library to understand the mechanisms of recognition and signal transduction and study the physicochemical basic of the specificity; and (ii) in terms of applications, the relative simplicity of these peptides and the rise of the

  15. Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity.

    Science.gov (United States)

    Deli, Mária A; Veszelka, Szilvia; Csiszár, Boglárka; Tóth, Andrea; Kittel, Agnes; Csete, Mária; Sipos, Aron; Szalai, Anikó; Fülöp, Lívia; Penke, Botond; Abrahám, Csongor S; Niwa, Masami

    2010-01-01

    Endothelial cells of brain capillaries forming the blood-brain barrier play an important role in the pathogenesis and therapy of Alzheimer's disease. Amyloid-β (Aβ) peptides are key pathological elements in the development of the disease. A blood-brain barrier model, based on primary rat brain endothelial cells was used in which the barrier properties were induced by glial cells. The effects of amyloid peptides have been tested on cell viability and barrier functions. Aβ showed toxic effects on primary rat brain endothelial cells measured by MTT dye conversion and the lactate dehydrogenase release. Morphologically cytoplasmic vacuolization, disruption of the structure of cytoplasmic organelles and tight junctions could be observed in brain endothelial cells. Treatment with Aβ1-42 decreased the electrical resistance, and increased the permeability of brain endothelial cell monolayers for both fluorescein and albumin. Serum amyloid P component which stabilizes Aβ fibrils in cortical amyloid plaques and cerebrovascular amyloid deposits significantly potentiated the barrier-weakening effect of Aβ1-42. Sulfated polysaccharide pentosan could decrease the toxic effects of Aβ peptides in brain endothelial cells. It could also significantly protect the barrier integrity of monolayers from damaging actions of peptides. Pentosan modified the size, and significantly decreased the number of amyloid aggregates demonstrated by atomic force microscopy. The present data further support the toxic effects of amyloid peptides on brain endothelial cells, and can contribute to the development of molecules protecting the blood-brain barrier in Alzheimer's disease.

  16. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  17. Antimicrobial peptides in Echinoderms

    Directory of Open Access Journals (Sweden)

    C Li

    2010-05-01

    Full Text Available Antimicrobial peptides (AMPs are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, dissimilar to other known AMPs. A family of heterodimeric AMPs, named centrocins, are also present in S. droebachiensis. Lysozymes and fragments of larger proteins, such as beta-thymocins, actin, histone 2A and filamin A have also been shown to display antimicrobial activities in echinoderms. Future studies on AMPs should be aimed in revealing how echinoderms use these AMPs in the immune response against microbial pathogens.

  18. Avian host defense peptides.

    Science.gov (United States)

    Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

    2013-11-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds.

  19. The P42 peptide and Peptide-based therapies for Huntington's disease.

    Science.gov (United States)

    Marelli, Cecilia; Maschat, Florence

    2016-03-17

    Huntington's disease (HD) is a progressive neurodegenerative hereditary disease clinically characterised by the presence of involuntary movements, behavioural problems and cognitive decline. The disease-onset is usually between 30 and 50 years of age. HD is a rare disorder affecting approximately 1.3 in 10,000 people in the European Union. It is caused by an expanded CAG repeat in the first exon of the Huntingtin (HTT) gene, leading to an abnormal form of the Huntingtin protein (Htt) (polyQHtt), containing N-terminus, enlarged polyglutamine strands of variable length that stick together to form aggregates and nuclear inclusions in the damaged brain cells. Treatments currently used for Huntington's disease are symptomatic and aimed at temporally relieving the symptoms of the disease; although some promising therapies are on study, there is no drug capable of stopping disease progression either in the form of delaying onset or slowing disability progression. The utilization of peptides interacting with polyQ stretches or with Htt protein to prevent misfolding and aggregation of the expanded polyQ protein is a fascinating idea, because of low potential toxicity and ability to target very initial steps in the pathophysiological cascade of the disease, such as aggregation or cleavage process. Indeed, several therapeutic peptides have been developed and were found to significantly slow down the progression of symptoms in experimental models of Huntington's disease. This review is essentially focusing on the latest development concerning peptide strategy. In particular, we focused on a 23aa peptide P42, which is a part of the Htt protein. It is expected to work principally by preventing the abnormal Htt protein from sticking together, thereby preventing pathological consequences of aggregation and improving the symptoms of the disease. In the meantime, as P42 is part of the Htt protein, some therapeutic properties might be linked to the physiological actions of the

  20. [C-peptide physiological effects].

    Science.gov (United States)

    Shpakov, A O; Granstrem, O K

    2013-02-01

    In the recent years there were numerous evidences that C-peptide, which was previously considered as a product of insulin biosynthesis, is one of the key regulators of physiological processes. C-peptide via heterotrimeric G(i/o) protein-coupled receptors activates a wide range of intracellular effector proteins and transcription factors and, thus, controls the inflammatory and neurotrophic processes, pain sensitivity, cognitive function, macro- and microcirculation, glomerular filtration. These effects of C-peptide are mainly expressed in its absolute or relative deficiency occurred in type 1 diabetes mellitus and they are less pronounced when the level of C-peptide is close to normal. Replacement therapy with C-peptide prevents many complications of type 1 diabetes, such as atherosclerosis, diabetic peripheral neuropathy, and nephropathy. C-peptide interacts with the insulin hexamer complexes and induces their dissociation and, as a result, regulates the functional activity of the insulin signaling system. At the same time, C-peptide at the concentrations above physiological may demonstrate pro-inflammatory effects on the endothelial cells and cause atherosclerotic changes in the vessels, which should be considered in the study of pathogenic mechanisms of complications of type 2 diabetes mellitus, where the level of C peptide is increased, as well as in the development of approaches for C-peptide application in clinic. This review is devoted contemporary achievements and unsolved problems in the study of C-peptide, as an important regulator of physiological and biochemical processes.

  1. Detection and Significance of Brain Natriuretic Peptide Level in Normal Late Pregnant Women with Twin Pregnancy%正常双胎晚期妊娠孕妇氨基末端脑钠肽前体水平的检测及意义∗

    Institute of Scientific and Technical Information of China (English)

    游一平; 李晨辉; 唐雅兵; 王诗章

    2014-01-01

    目的探讨正常双胎晚期妊娠孕妇氨基末端脑钠肽前体(NT-proBNP)水平的正常值范围,为临床应用提供指导。方法用免疫电化学发光法测定本院758例正常双胎晚期妊娠孕妇血清 NT-proBNP水平,并根据孕周不同进一步将758例正常双胎晚期妊娠孕妇分为3个亚组,即 A组(孕28~31+6周)、B组(32~35+6周)、C组(≥孕36周),并比较三组NT-proBNP水平。结果正常双胎晚期妊娠孕妇NT-proBNP水平为(60.44±42.02)pg/mL,A、B、C三组血清NT-proBNP值分别为(29.55±25.49)pg/mL、(86.28±54.25)pg/mL、(66.69±31.44)pg/mL,A组与B、C组比较,A组血清NT-proBNP水平明显低于B组与C组,且差异有显著性(P0.05)。结论本组测得正常双胎晚期妊娠孕妇 NT-proBNP水平,样本量较大,其结果可以初步确立正常双胎晚期妊娠孕妇NT-proBNP参考值的范围。%Obj ective]To explore normal value range of brain natriuretic peptide(amino terminal pro-brain natriuretic peptide,NT-proBNP)level in normal late pregnant women with twin pregnancy so as to provide the guidance for clinical application.[Methods]Serum NT-proBNP level in 758 normal twin pregnant women of our hospital was determined by immune electrochemical luminescence method.According to gestational weeks,758 normal late pregnant women with twin pregnancy were further divided into 3 subgroups including group A(28~31+6 gestational weeks),group B(32~35+6 gestational weeks)and group C(≥36 gestational weeks).The levels of NT-proBNP among 3 groups were compared.[Results]The levels of NT-proBNP in normal late preg-nant women with twin pregnancy were (60.44±42.02)pg/mL,and those in group A,B and C were (29.55± 25.49)pg/mL,(86.28±54.25)pg/mL and (66.69±31.44)p/mL,respectively.The levels of NT-proBNP in group A were obviously lower than those in group B and C,and there was significant difference(P 0.05).[Conclusion]In this group, NT-proBNP level in normal late pregnant women with twin pregnancy is determined

  2. 重组人脑利钠肽对动脉硬化大鼠血管内皮功能的影响%The effects of Brain Natriuretic Peptide on the function of rats arteriosclerosis model vascular endothelial

    Institute of Scientific and Technical Information of China (English)

    周琳; 张静; 袁天阳; 李扬雪; 徐艳玲; 戴琎

    2013-01-01

    目的 探讨rhBNP对动脉粥样硬化(AS)大鼠模型血管内皮功能的影响.方法 40只健康wistar大鼠,随机分为对照组、模型组、处理组各8只.处理组分别给予硝酸酯类、阿魏酸钠、重组人脑利钠肽皮下注射.采用酶联免疫吸附(ELISA)方法测定各组大鼠处理前后血清中血栓素B2(TXB2)和6-酮前列腺素F1a(6-Keto-PGF1a)的含量,并且光镜下观察各组处理前后大鼠的主动脉内膜细胞的变化.结果 1)处理组药物治疗后,血清中TXB2均下降、6-Keto-PGF1a均升高,与治疗前比较有统计学差异(P0.05);3)光镜的观察结果提示:模型组血管管腔内有附壁斑块;平滑肌细胞排列紊乱;处理组内膜较光滑,局部有MC粘附,偶可见EC缺失,但好于模型组,各处理组之间未见明显差别.结论 rhBNP通过保护血管内皮功能具有抗动脉粥样硬化的作用.%Objective The effects of Brain Natriuretic Pcptidc on the function of rats arteriosclerosis model vascular endothelial. Methods 40 healthy wistar rats, divided into five groups at random, eight rats in contorl group, eight in model group,each of the treatment group of nitratcs(Hua rcn xin shu),Sodium Fcrulatc(Haisi) ., rhBNP (xinhuosu) model group were eight rats. Adopt enzyme-linked immunosorbent adsorption (ELISA) methods to determine each rat treatment and scrum blood TXB2 and 6-Kcto-PGFla content,and light-microscopy each rat before and after processing the aortic lining cells changes. Results a. The treatment group scrum TXB2 and 6-Kcto-PGFla levels obviously different than bcforc(P 0. 05). c. Optical microscope observations, the control group vascular lumen, no calcium sediment, big plaques can be seen. Smooth muscle cells is boom and ectoblast is conjunction tissue, arranging disorganized. The treatment group is smoother,local macrophagc adhesion,visible EC missing,but better than model group,and the treatment group showed no significant difference between. Conclusion rhBNP can not

  3. Novel Functional Association of Serine Palmitoyltransferase Subunit 1-A Peptide in Sphingolipid Metabolism with Cytochrome P4501A1 Transactivation and Proliferative Capacity of the Human Glioma LN18 Brain Tumor Cell Line

    Directory of Open Access Journals (Sweden)

    J. Stewart

    2006-09-01

    Full Text Available Some chemical modulators of cytochrome P4501A1, Cyp1A1, expression also perturb the activity of serine palmitoyltransferase, SPT, a heterodimeric protein responsible for catalyzing the first reaction in sphingolipid biosynthesis. The effect of altered SPT activity on Cyp1A1 expression has generally been attributed to changes in the composition of bioactive sphingolipids, generated downstream in the SPT metabolic pathway, but the precise mechanism remains poorly defined. A generally accepted model for chemical-induced transactivation of the Cyp1A1 gene involves intracellular signaling mediated by proteins including the arylhydrocarbon receptor, AhR, whose interaction with the 90 kilo Dalton heat shock protein, Hsp90, is essential for maintaining a high affinity ligandbinding receptor conformation. Because ligand-induced Cyp1A1 expression is important in the bioactivation of environmentally relevant compounds to genotoxic derivatives capable of perturbing cellular processes, binding to Hsp90 represents an important regulatory point in the cytotoxicity process. In the present study, based on evidence that indicates subunit 1 of serine palmitoyltransferase, SPT1, interacts with Hsp90, both ligand-induced Cyp1A1 transactivation and capacity for proliferation were evaluated using the wild type Glioma LN18 human brain cancer cell line and its recombinant counterparts expressing green fluorescent SPT1 fusion proteins. Exposure to the prototypical Cyp1A1 inducer, 3-methylcholanthrene, 3-MC, resulted in the translocation of SPT1 from a primarily cytoplasmic domain to sites of focal adhesion complexes. Immunolabel for Hsp90, which was dispersed throughout the cell, became primarily cytoplasmic, while the distribution of AhR remained unaffected. When compared to the wild type, cells transfected with recombinant SPT1-GFP vectors had significantly attenuated levels of 3-MC-induced Cyp1A1 mRNA, as determined by quantitative reverse transcription PCR. Although

  4. [The role of B type natriuretic peptide in the assessment of post myocardial infarction prognosis].

    Science.gov (United States)

    Ben Halima, A; Ibn el Hadj, Z; Chrigui, R; Kammoun, I; Lefi, A; Chine, S; Gargouri, S; Keskes, H; Kachboura, S

    2006-10-01

    Recently cardiac peptides have received close attention as cardiovascular markers. Brain (B type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Previous studies have shown that this hormone can provide prognostic information in patients with myocardial infarction. The aim of this review is to evaluate the impact of plasma levels of BNP on prediction of left ventricular ejection fraction and remodelling and major cardiac events after myocardial infarction.

  5. Curative Effect of Recombinant Human Brain Natriuretic Peptide Compared with Milrinone on Refractory Elderly Congestive Heart Failure%重组人脑钠肽和米力农治疗老年充血性心力衰竭的比较

    Institute of Scientific and Technical Information of China (English)

    黄馨

    2012-01-01

    目的:本文应用重组人脑钠肽(rhBNP) 和米力农对顽固性的老年充血性心力衰竭进行治疗,并观察临床治疗的疗效比较.方法:将30 例老年充血性心力衰竭患者随机分为两组,一组在常规治疗的基础上加用米力农,另一组在常规治疗的基础上加用重组人脑钠肽,观察治疗前后两组患者的临床症状、体征、心功能等的改善情况.结果:两组治疗前后,重组人脑钠肽疗效明显优于米力农组,两者比较,差异有统计学意义.结论:重组人脑钠肽治疗老年充血性心力衰竭疗效确切,较米力农改善更加明显.%Objective:To compare the clinical curative effect of treatment recombinant human brain natriuretic peptide (rhBNP) and milrinone in treatment of refractory elderly congestive heart failure patients.Methods:30 elderly patients with congestive heart failure on the basis of the conventional treatment were randomly divided into two groups (rhBNP group and milrinone group).Observe the patient's clinical symptoms,signs,cardiac function before and after treatment.Results:Clinical symptoms, signs, cardiac function,rhBNP group were significantly better than those in the milrinone group(all P<0.05).Conclusion:The clinical curative effect of rhBNP in treatment of refractory elderly congestive heart failure patients is superior to milrinone.

  6. Efficacy of recombinant human brain natriuretic peptide on acute heart failure with renal function insufficiency%重组人脑钠肽治疗急性心力衰竭合并肾功能不全的近期疗效观察

    Institute of Scientific and Technical Information of China (English)

    卢鑫; 胡桃红; 谢晓春; 刘胜林; 李慧君; 张玮; 王晶

    2014-01-01

    Objective To analyze the efficacy of recombinant human brain natriuretic peptide (rhBNP) treating congestive heart failure complicated with renal failure.Methods A retrospective analysis of 105 cases of heart failure and renal failure patients were randomly divided into two groups:group rhBNP (55 cases,on the basis of conventional therapy plus rhBNP) and routine treatment group (50 cases,treated with routine therapy).The effect of recombinant human brain natriuretic peptide [0.007 5 μg/(kg · min) micro pump intravenous infusion,once a day,each lasting approximately 10 hours,7 days for a course of treatment] was recorded before treatment,7 days and 3 months after treatment,including left ventricular ejection fraction,left ventricular end diastolic volume,left ventricular systolic end diastolic volume,24 hour urine volume,blood urea nitrogen,serum creatinine,serum cystatin C,NT-proBNP and creatinine clearance rate.Results Compared with routine therapy group after 7 days,NT-proBNP[(1 516 ±432)ng/L vs (4 951 ± 1 314)ng/L],the left ventricular ejection fraction[(46.9 ±6.8)% vs (30.6 ± 2.5) %],left ventricular end diastolic diameter [(50 ± 3) mm vs (57 ± 5) mm],left ventricular end systolic diameter [(35 ±6)mm vs (43 ±3)mm],24 hours urine volume [(975 ± 172) ml vs (786 ± 143)ml],urea nitrogen [(7.3 ± 2.3)mmol/L vs (12.9 ± 3.2)mmol/L],serum creatinine [(93 ± 8)μmol/L vs (234 ± 69) μmol/L],glomerular filtration rate [(46 ±6)ml/min vs (34 ±3)ml/min],serum cystatin C[(1.4 ± 0.1)mg/L vs (3.2 ± 1.9)mg/L] had significant differences between the two groups (P < 0.05).Conclusion The recombinant human brain natriuretic peptide is safe and can improve the renal function in chronic heart failure.%目的 观察重组人脑钠肽(rhBNP)治疗心力衰竭合并肾功能不全的近期疗效.方法 回顾性分析心力衰竭合并肾功能不全的患者105例,根据不同治疗分为2组,常规治疗组50例,给予常规治疗;rhBNP组55例,常规治疗

  7. Clinical Study of Brain Natriuretic Peptide and Blood Lactate Clearance Rate in Type A Aortic Dissection of Postoperative Respiratory Insufficiency%脑钠肽与血乳酸清除率在A型主动脉夹层术后呼吸功能不全的临床研究

    Institute of Scientific and Technical Information of China (English)

    欧阳晓仙; 刘易林; 李莉; 吴金平; 廖成全

    2016-01-01

    Objective:To observe dynamic changes of brain natriuretic peptide(BNP) levels and blood lactate clearance rate for postoperative respiratory insufficiency of type A aortic dissection surgery,in order to assess the extent of lung injury,guide the role of weaning.Method:A total of 42 patients with postoperative respiratory insufficiency of type A aortic dissection surgery in our hospital were selected from October 2010 to October 2015.According to patients with oxygen index to the acute lung injury group (ALI) (oxygenation index: 200 mm Hg≤PaO2/FiO2≤300 mm Hg) and ARDS group (PaO2/FiO2≤200 mm Hg),according to ventilator weaning results for the weaning success group (successful weaning and extubation and 48 h without complex in ventilation or support) the weaning failure group (48 h after weaning need to be ventilated again).Blood lactic acid,blood gas analysis and brain natriuretic peptide were observed at transferred,6,24,48 h,3 d until turn out.Result:All patients with postoperative respiratory insufficiency of type A aortic dissection surgery had higher blood lactic acid in the patients with respiratory insufficiency after operation,into the obvious,then gradually decreased,BNP levels increased gradually,the ALI group reached the peak at 3 d and 5 d dropped significantly, oxygenation index improved significantly in the ARDS group reached the peak at the 5 d,7 d dropped significantly, oxygenation index improved significantly.The weaning successful group was compared with the weaning failure group,BNP level was significantly lower,blood lactate clearance rate was higher and the differences between the two groups had statistical significance(P<0.05).Conclusion:Respiratory function of patients with the more severe,in patients with brain natriuretic peptide content is higher and the blood lactic acid clearance rate is low, postoperative weaning more difficult,BNP levels and blood lactic acid clearance rate is postoperative respiratory insufficiency of type A

  8. Impacts on the Contents of Brain-Gut Peptides(GAS,NPY and CGRP)in Colonic Mucosa of Depression Model Rats Treated with Different Electroacupuncture%不同电针对抑郁模型大鼠结肠黏膜脑肠肽GAS、NPY、CGRP含量的影响

    Institute of Scientific and Technical Information of China (English)

    滕金艳; 李志刚; 白妍; 赛音朝克图

    2013-01-01

    目的 观察不同电针"百会""印堂"对抑郁模型大鼠结肠黏膜三种胃肠道相关脑肠肽胃泌素(GAS)、神经肽Y(NPY)及降钙素基因相关肽(CGRP)的影响,为揭示针刺治疗抑郁症胃肠道躯体化症状作用途径提供实验依据,并比较不同电针的作用效果.方法 将60只健康SD大鼠随机分为空白组、模型组、百优解组、脉冲电针组、音乐电针组,每组12只.采用慢性不可预见的温和刺激结合孤养方法制备抑郁模型.百忧解组每天将百忧解以生理盐水配制灌胃给药.脉冲电针组针刺大鼠"百会"和"印堂"穴,接脉冲电针治疗仪.音乐电针组取穴同脉冲点针组,接音乐电针治疗仪.采用放射免疫法测定各组大鼠结肠黏膜GAS、NPY、CGRP含量.结果 模型组与空白组相比,大鼠结肠黏膜GAS含量显著降低(P<0.05),NPY含量显著升高(P<0.05),CGRP含量极显著升高(P<0.01);脉冲电针组、音乐电针组及百忧解组与模型组相比,大鼠结肠黏膜GAS含量显著升高(P<0.05或P<0.01),NPY含量显著降低(P<0.05或P<0.01),CGRP含量显著降低(P<0.05或P<0.01);音乐电针组与脉冲电针组相比,大鼠结肠黏膜CGRP含量降低水平更为显著(P<0.05).结论 电针治疗可通过调整抑郁后胃肠道兴奋性激素与抑制性激素的失平衡来影响肠道中脑肠肽含量,从而调控脑-肠轴,使抑郁后胃肠功能紊乱状态得到改善,而且音乐电针组优于脉冲电针组.%Objective To observe the impacts on three gastrointestinal tract related brain — gut pep-tides , named gastrin( GAS ), nenropeptide Y( NPY ) and calcitonin gene related peptide( CGRP ) in colonic mucosa treated with electroacupimctnre( EA )at Baihni( GV20 Jand Yintang( Extra Jin depression model rats so as to discover the experimental evidences for acupuncture effective approach in the treatment of gastrointestinal somatization symptoms of depression and make the comparison of the effects

  9. Neuropeptides and the microbiota-gut-brain axis.

    Science.gov (United States)

    Holzer, Peter; Farzi, Aitak

    2014-01-01

    Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. Current efforts in elucidating the implication of neuropeptides in the microbiota-gut-brain axis address four information carriers from the gut to the brain (vagal and spinal afferent neurons; immune mediators such as cytokines; gut hormones; gut microbiota-derived signalling molecules) and four information carriers from the central nervous system to the gut (sympathetic efferent neurons; parasympathetic efferent neurons; neuroendocrine factors involving the adrenal medulla; neuroendocrine factors involving the adrenal cortex). Apart from operating as neurotransmitters, many biologically active peptides also function as gut hormones. Given that neuropeptides and gut hormones target the same cell membrane receptors (typically G protein-coupled receptors), the two messenger roles often converge in the same or similar biological implications. This is exemplified by NPY and peptide YY (PYY), two members of the PP-fold peptide family. While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides

  10. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  11. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  12. Antitumor Peptides from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Mi Sun

    2011-10-01

    Full Text Available The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.

  13. The Pig PeptideAtlas

    DEFF Research Database (Denmark)

    Hesselager, Marianne Overgaard; Codrea, Marius; Sun, Zhi;

    2016-01-01

    underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within...... the veterinary proteomics domain, and this article demonstrates how the expression of isoform-unique peptides can be observed across distinct tissues and body fluids. The Pig PeptideAtlas is a unique resource for use in animal proteome research, particularly biomarker discovery and for preliminary design of SRM...

  14. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective.......This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  15. Predictive value of natriuretic peptides in dogs with mitral valve disease

    DEFF Research Database (Denmark)

    Tarnow, Inge; Olsen, Lisbeth Høier; Kvart, Clarence;

    2009-01-01

    Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic...... peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs. Twenty seven CKCS and ten control dogs were re-examined 4 years after the initial examination...

  16. Metabolism of cryptic peptides derived from neuropeptide FF precursors: the involvement of insulin-degrading enzyme.

    Science.gov (United States)

    Grasso, Giuseppe; Mielczarek, Przemyslaw; Niedziolka, Magdalena; Silberring, Jerzy

    2014-09-22

    The term "cryptome" refers to the subset of cryptic peptides with bioactivities that are often unpredictable and very different from the parent protein. These cryptic peptides are generated by proteolytic cleavage of proteases, whose identification in vivo can be very challenging. In this work, we show that insulin-degrading enzyme (IDE) is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor), generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate. The reported experimental findings support the increasingly accredited hypothesis, according to which, due to its wide substrate selectivity, IDE is involved in a wide variety of physiopathological processes.

  17. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Akira Yano

    2015-01-01

    Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brainpeptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

  18. Brain Autopsy

    Science.gov (United States)

    ... why a family should consider arranging for a brain autopsy upon the death of their loved one. To get a definitive ... study of tissue removed from the body after death. Examination of the whole brain is important in understanding FTD because the patterns ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...

  20. Brain Basics

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    Full Text Available ... and are working to compare that with brain development in people mental disorders. Genes and environmental cues both help to direct ... comparing such children to those with normal brain development may help scientists to pinpoint when and where mental disorders begin and perhaps how to slow or stop ...

  1. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

    Directory of Open Access Journals (Sweden)

    Carmela eGiordano

    2014-04-01

    Full Text Available Various ketogenic diet (KD therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs. In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the

  2. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  3. Brain peroxisomes.

    Science.gov (United States)

    Trompier, D; Vejux, A; Zarrouk, A; Gondcaille, C; Geillon, F; Nury, T; Savary, S; Lizard, G

    2014-03-01

    Peroxisomes are essential organelles in higher eukaryotes as they play a major role in numerous metabolic pathways and redox homeostasis. Some peroxisomal abnormalities, which are often not compatible with life or normal development, were identified in severe demyelinating and neurodegenerative brain diseases. The metabolic roles of peroxisomes, especially in the brain, are described and human brain peroxisomal disorders resulting from a peroxisome biogenesis or a single peroxisomal enzyme defect are listed. The brain abnormalities encountered in these disorders (demyelination, oxidative stress, inflammation, cell death, neuronal migration, differentiation) are described and their pathogenesis are discussed. Finally, the contribution of peroxisomal dysfunctions to the alterations of brain functions during aging and to the development of Alzheimer's disease is considered.

  4. Valproate and copper accelerate TRH-like peptide synthesis in male rat pancreas and reproductive tissues.

    Science.gov (United States)

    Pekary, A E; Stevens, S A; Sattin, A

    2006-11-01

    Treatment with valproate (Valp) facilitates the synthesis of TRH-like peptides (pGlu-X-Pro-NH(2)) in rat brain where "X" can be any amino acid residue. Because high levels of TRH-like peptides occur in the pancreas and pGlu-Glu-Pro-NH(2) (Glu-TRH) has been shown to be a fertilization promoting peptide, we hypothesized that these peptides mediate some of the metabolic and reproductive side effects of Valp. Male WKY rats were treated with Valp acutely (AC), chronically (CHR) or chronically followed by a 2 day withdrawal (WD). AC, CHR and WD treatments significantly altered TRH and/or TRH-like peptide levels in pancreas and reproductive tissues. Glu-TRH was the predominant TRH-like peptide in epididymis, consistent with its fertilization promoting activity. Glu-TRH levels in the epididymis increased 3-fold with AC Valp. Phe-TRH, the most abundant TRH-like peptide in the pancreas, increased 4-fold with AC Valp. Phe-TRH inhibits both basal and TRH-stimulated insulin release. Large dense core vesicles (LDCV's) contain a copper-dependent enzyme responsible for the post-translational processing of precursors of TRH and TRH-like peptides. Copper (500 microM) increased the in vitro C-terminal amidation of TRH-like peptides by 8- and 4-fold during 24 degrees C incubation of homogenates of pancreas and testis, respectively. Valp (7 microM) accelerated 3-fold the processing of TRH and TRH-like peptide precursors in pancreatic LDCV's incubated at 24 degrees C. We conclude that copper, an essential cofactor for TRH and TRH-like peptide biosynthesis that is chelated by Valp, mediates some of the metabolic and reproductive effects of Valp treatment via acceleration of intravesicular synthesis and altered release of these peptides.

  5. A metallothionein mimetic peptide protects neurons against kainic acid-induced excitotoxicity

    DEFF Research Database (Denmark)

    Sonn, Katrin; Pankratova, Stanislava; Korshunova, Irina

    2010-01-01

    Metallothioneins I and II (MTI/II) are metal-binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the beta-domain of MT-II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate the neuroprotect......Metallothioneins I and II (MTI/II) are metal-binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the beta-domain of MT-II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate...

  6. Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.

    Directory of Open Access Journals (Sweden)

    Arnab Bhattacherjee

    2013-10-01

    Full Text Available The binding of short disordered peptide stretches to globular protein domains is important for a wide range of cellular processes, including signal transduction, protein transport, and immune response. The often promiscuous nature of these interactions and the conformational flexibility of the peptide chain, sometimes even when bound, make the binding specificity of this type of protein interaction a challenge to understand. Here we develop and test a Monte Carlo-based procedure for calculating protein-peptide binding thermodynamics for many sequences in a single run. The method explores both peptide sequence and conformational space simultaneously by simulating a joint probability distribution which, in particular, makes searching through peptide sequence space computationally efficient. To test our method, we apply it to 3 different peptide-binding protein domains and test its ability to capture the experimentally determined specificity profiles. Insight into the molecular underpinnings of the observed specificities is obtained by analyzing the peptide conformational ensembles of a large number of binding-competent sequences. We also explore the possibility of using our method to discover new peptide-binding pockets on protein structures.

  7. Hormones and the blood-brain barrier.

    Science.gov (United States)

    Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

    2015-03-01

    Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

  8. Quantification of Brain Access of Exendin-4 in the C57BL Mouse Model by SPIM Fluorescence Imaging and the Allen Mouse Brain Reference Model

    DEFF Research Database (Denmark)

    Jensen, Casper Bo; Secher, Anna; Hecksher-Sørensen, Jacob;

    2015-01-01

    With the recent advance in 3D microscopy such as Single Plane Illumination Microscopy (SPIM) it is possible to obtain high resolution image volumes of the entire mouse brain. These data can be used to study the access of several peptides such as the glucagon-like peptide-1 (GLP-1) analogue Exendin...... construct a SPIM brain atlas based on the Allen mouse brain 3D reference model and use it to analyze the access of peripherally injected Exendin-4 into the brain compared to a negative control group. The constructed atlas consists of an average SPIM volume obtained from eight C57BL mouse brains using group......-wise registration. A cross-modality registration is performed between the constructed average volume and the Allen mouse brain reference model to allow propagation of annotations to the SPIM average brain. Finally, manual corrections of the annotations are performed and validated by visual inspection. The study...

  9. Endocrine cells producing regulatory peptides.

    Science.gov (United States)

    Solcia, E; Usellini, L; Buffa, R; Rindi, G; Villani, L; Zampatti, C; Silini, E

    1987-07-15

    Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

  10. Endogenous opioid peptides and epilepsy

    NARCIS (Netherlands)

    J. Haffmans (Judith)

    1985-01-01

    textabstractIn recent years a large number of pept:ides, many of which were originall.y characterized in non-neural tissues, have been reported to be present in the central nervous system ( CNS) . The detection of these peptides within the CNS has raised many questions regarding their source and mec

  11. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  12. Peptide Antibiotics for ESKAPE Pathogens

    DEFF Research Database (Denmark)

    Thomsen, Thomas Thyge

    and toxicity by utilizing of the fruit fly Drosophila melanogaster as a whole animal model. This was carried out by testing of antimicrobial peptides targeting Gram-positive bacteria exemplified by the important human pathogen methicillin resistant S. aureus (MRSA). The peptide BP214 was developed from...

  13. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...

  14. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the uni

  15. Proteomic analysis of normal murine brain parts.

    Science.gov (United States)

    Taraslia, Vasiliki K; Kouskoukis, Alexandros; Anagnostopoulos, Athanasios K; Stravopodis, Dimitrios J; Margaritis, Lukas H; Tsangaris, George Th

    2013-01-01

    Murine brain is an excellent tool for studying protein expression and brain function in mammals. Although mice are an extensively used model to recapitulate various pathological conditions, the proteome of the normal mouse brain has not been yet reported. In the present study, we identified the total proteins of different parts of the brain of CB7BL/6 mice, a widely used strain, by applying proteomic methodologies. The adult mouse brain was dissected anatomically into the following regions: frontal cortex, olfactory bulb, hippocampus, midbrain, cerebellum, hypothalamus and medulla. Total protein extracts of these regions were separated by two-dimensional gel electrophoresis and analyzed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, following in-gel digestion with trypsin. Protein identification was carried out by peptide mass fingerprint. Thus, 515 different single-gene products were identified in total, 54 expressed specifically in the olfactory bulb, 62 in the hippocampus, 36 in the frontal cortex, five in the cerebellum, nine in the midbrain, eight in the hypothamamus and 10 in the medulla. The majority of the proteins were enzymes, structural proteins and transporters. Moreover, the distribution of these molecules appears to exhibit direct correlation with the function of the brain regions where they were expressed. This study leads to the complete characterization of the normal mouse brain proteome as well as the protein expression profile of the different brain regions. These results will aid in addressing unmet scientific needs regarding physiological and pathological brain functions.

  16. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  17. The role of food intake regulating peptides in cardiovascular regulation.

    Science.gov (United States)

    Mikulášková, B; Maletínská, L; Zicha, J; Kuneš, J

    2016-11-15

    Obesity is a risk factor that worsens cardiovascular events leading to higher morbidity and mortality. However, the exact mechanisms of relation between obesity and cardiovascular events are unclear. Nevertheless, it has been demonstrated that pharmacological therapy for obesity has great potential to improve some cardiovascular problems. Therefore, it is important to determine the common mechanisms regulating both food intake and blood pressure. Several hormones produced by peripheral tissues work together with neuropeptides involved in the regulation of both food intake and blood pressure. Anorexigenic (food intake lowering) hormones such as leptin, glucagon-like peptide-1 and cholecystokinin cooperate with α-melanocyte-stimulating hormone, cocaine- and amphetamine-regulated peptide as well as prolactin-releasing peptide. Curiously their collective actions result in increased sympathetic activity, especially in the kidney, which could be one of the factors responsible for the blood pressure increases seen in obesity. On the other hand, orexigenic (food intake enhancing) peptides, especially ghrelin released from the stomach and acting in the brain, cooperates with orexins, neuropeptide Y, melanin-concentrating hormone and galanin, which leads to decreased sympathetic activity and blood pressure. This paradox should be intensively studied in the future. Moreover, it is important to know that the hypothalamus together with the brainstem seem to be major structures in the regulation of food intake and blood pressure. Thus, the above mentioned regions might be essential brain components in the transmission of peripheral signals to the central effects. In this short review, we summarize the current information on cardiovascular effects of food intake regulating peptides.

  18. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  19. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  20. Effect of Needling the Points of Foot-Yangming Channel on the Gastric Motility,and Brain-gut Peptides in Rat%针刺足阳明经穴对大鼠胃运动及脑肠肽的影响

    Institute of Scientific and Technical Information of China (English)

    易受乡; 林亚平; 严洁; 常小荣; 杨昱

    2001-01-01

    Objective:To clarify whether the peptides are the substantial elements linking stomach and Foot-yangming Channel.Methods:The model of gastric mucous damage(GMD) was induced with infusing pure alcohol into gastric cavity.The change rate of frequency and amplitude of gastric motility was monitored by the method of “Gas Balloon”.Content of substance P(SP) and MTL、GAS in antrum and medulla was measured by radioimmunoassay.Results:Inhibit effect of the frequency and amplitude of gastric motility was showed.After needling the points of Sibai,Tiansu,Zusanli,the gastric motility restored to normal.At the same time levels of SP、MTL and GAS in antrum and in medulla varied analogously.The change of MTL in antrum was found in group of Sibai mostly;the change of SP in antrum mostly in group of Tiansu;the change either SP、MTL or GAS was found in group of Zusanli.Conclusion:There exists certain parallel relationship between level of brain-gut peptiads in antrum and medulla and gastric motility.It is suggested that SP and MTL may play a certain role in regulating stomach activity by needling the points of Foot-yangming Channel.But their involved peptides may be different.%目的:探讨针刺足阳明经穴对胃运动的调整作用与脑肠肽的关系。方法:以乙醇灌胃造成大鼠胃粘膜损伤模型,气囊法测量胃运动频率和波幅的变化率,采用放免分析法(RIA)检测大鼠胃窦及延髓内P物质(SP)、胃动素(MTL)及胃泌素(GAS)含量。结果:模型组胃运动频率和波幅呈抑制状态,针刺四白、天枢、足三里穴可促进胃运动恢复,与此同时胃窦、延髓内SP、MTL、GAS含量出现相应变化。三穴比较:四白主要影响胃窦MTL含量,天枢主要影响胃窦SP及延髓GAS含量,足三里穴对SP、MTL及GAS均有影响。结论:推测针刺足阳明经对胃运动的调整作用有脑肠肽参与,但上述三穴对胃运动的影响所涉及的脑肠肽不完全一致。

  1. Brain Basics

    Medline Plus

    Full Text Available ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ... Higher Death Rate Among Youth with Psychosis Delayed Walking Link ...

  2. Brain Basics

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    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... or-flight response and is also involved in emotions and memory. anterior cingulate cortex —Is involved in ...

  3. Brain Basics

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    Full Text Available ... Some people who develop a mental illness may recover completely; others may have repeated episodes of illness ... in early detection, more tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything ...

  4. Brain Basics

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    Full Text Available ... that contains codes to make proteins and other important body chemicals. DNA also includes information to control ... cells required for normal function and plays an important role during early brain development. It may also ...

  5. Brain Basics

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    Full Text Available ... of the cell from its surrounding environment and controls what enters and leaves the cell, and responds ... via axons) to form brain circuits. These circuits control specific body functions such as sleep and speech. ...

  6. Brain Basics

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    Full Text Available ... in early detection, more tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything ... can cause tremors or symptoms found in Parkinson's disease. Serotonin —helps control many functions, such as mood, ...

  7. Brain Basics

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    Full Text Available ... Offices and Divisions Careers@NIMH Advisory Boards and Groups Staff Directories Getting to NIMH National Institutes of ... electrical signals. The brain begins as a small group of cells in the outer layer of a ...

  8. Brain Basics

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    Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into ... factors that can affect our bodies, such as sleep, diet, or stress. These factors may act alone ...

  9. Purification and use of E. coli peptide deformylase for peptide deprotection in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia; Sonke, Theo; Quaedflieg, Peter J.; Janssen, Dick B.

    2013-01-01

    Peptide deformylases (PDFs) catalyze the removal of the formyl group from the N-terminal methionine residue in nascent polypeptide chains in prokaryotes. Its deformylation activity makes PDF an attractive candidate for the biocatalytic deprotection of formylated peptides that are used in chemoenzyma

  10. Peptidomic identification and biological validation of neuroendocrine regulatory peptide-1 and -2.

    Science.gov (United States)

    Yamaguchi, Hideki; Sasaki, Kazuki; Satomi, Yoshinori; Shimbara, Takuya; Kageyama, Haruaki; Mondal, Muhtashan S; Toshinai, Koji; Date, Yukari; González, Luis J; Shioda, Seiji; Takao, Toshifumi; Nakazato, Masamitsu; Minamino, Naoto

    2007-09-07

    Recent advances in peptidomics have enabled the identification of previously uncharacterized peptides. However, sequence information alone does not allow us to identify candidates for bioactive peptides. To increase an opportunity to discover bioactive peptides, we have focused on C-terminal amidation, a post-translational modification shared by many bioactive peptides. We analyzed peptides secreted from human medullary thyroid carcinoma TT cells that produce amidated peptides, and we identified two novel amidated peptides, designated neuroendocrine regulatory peptide (NERP)-1 and NERP-2. NERPs are derived from distinct regions of the neurosecretory protein that was originally identified as a product of a nerve growth factor-responsive gene in PC12 cells. Mass spectrometric analysis of the immunoprecipitate using specific antibodies as well as reversed phase-high performance liquid chromatography coupled with radioimmunoassay analysis of brain extract demonstrated the endogenous presence of NERP-1 and NERP-2 in the rat. NERPs are abundant in the paraventricular and supraoptic nuclei of the rat hypothalamus and colocalized frequently with vasopressin but rarely with oxytocin. NERPs dose-dependently suppressed vasopressin release induced by intracerebroventricular injection of hypertonic NaCl or angiotensin II in vivo. NERPs also suppressed basal and angiotensin II-induced vasopressin secretion from hypothalamic explants in vitro. Bioactivity of NERPs required C-terminal amidation. Anti-NERP IgGs canceled plasma vasopressin reduction in response to water loading, indicating that NERPs could be potent endogenous suppressors of vasopressin release. These findings suggest that NERPs are novel modulators in body fluid homeostasis.

  11. Neurogenic and neurotrophic effects of BDNF peptides in mouse hippocampal primary neuronal cell cultures.

    Directory of Open Access Journals (Sweden)

    Maria del Carmen Cardenas-Aguayo

    Full Text Available The level of brain-derived neurotrophic factor (BDNF, a member of the neurotrophin family, is down regulated in Alzheimer's disease (AD, Parkinson's disease (PD, depression, stress, and anxiety; conversely the level of this neurotrophin is increased in autism spectrum disorders. Thus, modulating the level of BDNF can be a potential therapeutic approach for nervous system pathologies. In the present study, we designed five different tetra peptides (peptides B-1 to B-5 corresponding to different active regions of BDNF. These tetra peptides were found to be non-toxic, and they induced the expression of neuronal markers in mouse embryonic day 18 (E18 primary hippocampal neuronal cultures. Additionally, peptide B-5 induced the expression of BDNF and its receptor, TrkB, suggesting a positive feedback mechanism. The BDNF peptides induced only a moderate activation (phosphorylation at Tyr 706 of the TrkB receptor, which could be blocked by the Trk's inhibitor, K252a. Peptide B-3, when combined with BDNF, potentiated the survival effect of this neurotrophin on H(2O(2-treated E18 hippocampal cells. Peptides B-3 and B-5 were found to work as partial agonists and as partial antagonists competing with BDNF to activate the TrkB receptor in a dose-dependent manner. Taken together, these results suggest that the described BDNF tetra peptides are neurotrophic, can modulate BDNF signaling in a partial agonist/antagonist way, and offer a novel therapeutic approach to neural pathologies where BDNF levels are dysregulated.

  12. Interaction of the Alzheimer Aβ(25-35) peptide segment with model membranes.

    Science.gov (United States)

    Cuco, Andreia; Serro, Ana Paula; Farinha, José Paulo; Saramago, Benilde; da Silva, Amélia Gonçalves

    2016-05-01

    Alzheimer's disease is characterized by the presence of amyloid plaques in the brain. The main components of these plaques are the Aβ(1-40) and Aβ(1-42) peptides but the Aβ(25-35) sequence is the most frequently studied fragment because it represents a biologically active region of the longer Aβ peptides. In the present work, the interactions of Aβ(25-35) peptide with model membranes were investigated, taking into consideration the aggregation state of the peptide. Monolayers and liposomes were taken as model membranes with two lipid compositions: the equimolar ternary mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol) and the equimolar POPC/SM binary mixture. The interaction of Aβ(25-35) with the monolayers, investigated at low concentrations (0.25-4μM), suggested a three step mechanism: adsorption-monomers or dimers adsorb at the polar region of the lipid monolayer; nucleation-adsorbed peptides act as nucleation sites for higher aggregates; and penetration-these aggregates insert in the hydrophobic region of the monolayer. Chol slightly enhances the peptide-lipid monolayer interaction. The large aggregates nucleated in the bulk solution evidenced a weak interaction with monolayers. The interaction of Aβ(25-35) with liposomes, followed by a Quartz Crystal Microbalance with Dissipation (QCM-D) in a large range of peptide concentrations (10-80μM), was very small, independently of the peptide concentration.

  13. Extending the scope of neuropeptidomics in the mammalian brain

    Directory of Open Access Journals (Sweden)

    Xiaozhe Zhang

    2014-06-01

    Full Text Available Neuropeptides are signaling molecules of intermediate size that are involved in neurotransmission and endocrine regulation. Complete monitoring of neuropeptides using neuropeptidomics approaches remains an important goal for describing targeted physiological regulation pathways. Considerable effort has been expended, particularly in terms of technique and methodology development, to extend the scope of neuropeptidomics. The capability of peptide characterization has been gradually improved, thus responding to increasing demands for broad detection and determination of various peptides. In this review, we discuss some achievements for the improvement of peptide identification coverage and their application for brain diseases and studying consequences of drug applications.

  14. Role of Troponins I and T and N-Terminal Prohormone of Brain Natriuretic Peptide in Monitoring Cardiac Safety of Patients With Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Trastuzumab: A Herceptin Adjuvant Study Cardiac Marker Substudy.

    Science.gov (United States)

    Zardavas, Dimitrios; Suter, Thomas M; Van Veldhuisen, Dirk J; Steinseifer, Jutta; Noe, Johannes; Lauer, Sabine; Al-Sakaff, Nedal; Piccart-Gebhart, Martine J; de Azambuja, Evandro

    2017-03-10

    Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study. Patients with missing marker assessments were excluded, resulting in 452 evaluable patients. A primary cardiac end point was defined as symptomatic congestive heart failure of New York Heart Association class III or IV, confirmed by a cardiologist, and a significant LVEF drop, or death of definite or probable cardiac causes. A secondary cardiac end point was defined as a confirmed significant asymptomatic or mildly symptomatic LVEF drop. Results Elevated baseline troponin I (> 40 ng/L) and T (> 14 ng/L), occurring in 56 of 412 (13.6%) and 101 of 407 (24.8%) patients, respectively, were associated with an increased significant LVEF drop risk (univariate analysis: hazard ratio, 4.52; P < .001 and hazard ratio, 3.57; P < .001, respectively). Few patients had their first elevated troponin value recorded during the study (six patients for troponin I and 25 patients for troponin T). Two patients developed a primary and 31 patients a secondary cardiac end point (recovery rate of 74%, 23 of 31). For NT-proBNP, higher increases from baseline were seen in patients with significant LVEF drop. Conclusion Elevated troponin I or T before trastuzumab is associated with increased risk for TRCD. A similar conclusion for NT-proBNP could not be drawn because of the lack of a well-established elevation threshold; however

  15. Relationship of plasma N-terminal pro-brain natriuretic peptide and cardiac function in patients with chronic kidney disease%慢性肾脏病患者血浆氨基末端前体脑钠肽与心功能的关系

    Institute of Scientific and Technical Information of China (English)

    向莉; 杨敏; 潘家荣

    2011-01-01

    Objective To study the relationship of plasma N-terminal pro-brain natriuretic peptide(NT-proBNP) and cardiac function in patients with chronic kidney disease(CKD). Methods Plasma NT-proBNP was examined in 152 CKD patients and 20 healthy subjects. The relationship of plasma NT-proBNP and echocardiographic and biochemistry parameter was analyzed. Results Plasma NT-proBNP level of CKD patients with heart failure was much higher than that of CKD cases in same stage but without heart failure. Plasma NT-proBNP level of CKD patients without heart failure increased with the decrease of the level of estimated glomerular filtration rate( eGFR),which was not in CKD patients with heart failure. NT-proBNP level was positively correlated with left atrial diameter (LAD), left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter (LVESD),but negatively correlated with left ventricular ejection frection(LVEF). Conclusion Plasma NT-proBNP is a sensitive marker for diagnosing early symptomless heart failure in CKD patients.%目的 研究血浆氨基末端前体脑钠肽(NT-proBNP)与心功能的关系.方法 采用固相免疫层析法检测152例不同分期慢性肾脏病(CKD)组患者与20例对照组血浆NT-proBNP水平,分析其与心脏彩超各指标、生化指标的关系.结果 伴有心衰的各期CKD患者NT-proBNP水平远高于同一分期无心衰患者;非心衰组CKD患者的NT-proBNP水平随着肾小球滤过率的下降逐渐升高;NT-proBNP水平与左房内径以及左室舒张末内径、左室收缩末内径均呈正相关,与心脏射血分数呈负相关.结论 NT-proBNP是早期诊断CKD患者无症状性心功能不全的敏感指标.

  16. Relationship of GRACE risk score with Plasma Brain Natriuretic Peptide and Myeloperoxidase in Patients with Non- ST Segment el-evation Acute Coronary Syndrome%非ST段抬高急性冠状动脉综合征患者GRACE危险积分与血浆 BNP、MPO的相关性

    Institute of Scientific and Technical Information of China (English)

    阚国庆; 高永; 王德启; 蔡忠贵; 王继征

    2016-01-01

    目的:探讨非 ST段抬高急性冠状动脉综合征(NSTE-ACS)患者全球急性冠状动脉事件注册(GRACE)评分与血浆脑钠肽( BNP)、髓过氧化酶(myeloperoxidase,MPO)水平的相关性。方法入选120例在我院住院的 NSTE-ACS患者,临床预测变量对其进行GRACE危险评分积分,并进行危险层次分层,入院后测定血浆 BNP、MPO水平。分析其与 GRACE危险积分不同层次之间的关系。结果①血浆 BNP、 MPO水平与GRACE危险积分呈正相关( r=0.71,P<0.05);随着 GRACE危险积分评分值增加,患者血浆 BNP、MPO水平亦逐渐升高;②随访期主要心血管事件发生率也增多(P <0.05)。结论 GRACE积分与BNP、MPO水平呈正相关,并与 NSTACS预后有关,能够对NSTEACS患者进行危险分层。%ObjectiveTo investigate the correlation of GRACE risk score and plasma brain natriuretic pep-tide ( BNP), myeloperoxidase in patients with non- ST segment elevation acute coronary syndrome.MethodsSelected 120 cases in NSTE-ACS patients in our hospital, clinical predictors its GRACE risk score points and dangerous level stratification, determination of plasma BNP, MPO levels after admission. Analyze the relationship between the different levels between the GRACE risk score.Results① The GRACE risk score is positively correlated with the plasma BNP and MPO levels ( r=0.71, P<0.05) ;② The incidence of MACE increased significantly with the rise of GRACE risk score and BNP, MPO levels.Conclusion: The higher GRACE risk score and BNP, MPO levels, the worse the prognosis, it could be use to predict the prognosis.

  17. The Value of Plasma Brain Natriuretic Peptide in Differentiating Acute Dyspnea from Aged Patients with Heart Failure%血液脑钠肽对鉴别老年心衰所致急性呼吸困难的价值

    Institute of Scientific and Technical Information of China (English)

    杨慧; 陈进军

    2009-01-01

    目的 探讨脑钠肽(BNP)对鉴别老年心衰所致急性呼吸困难的价值.方法 荧光免疫法测定145例以呼吸困难为主诉急诊人院或门诊老年患者血浆脑钠肽浓度.结果 心源性呼吸困难患者血液BNP浓度明显高于肺源性患者;BNP对于诊断左心衰有很强的预测价值,而早期诊断肺心病右心衰的价值尚待探讨;BNP值>100ng/L诊断心衰的灵敏度为94.1%,准确度93.1%,特异性79.5%,阳性预测值为91.3%,阴性预测值为85.4%.结论 快速检测血液BNP,用来诊断心力衰竭特别是左心衰,敏感、简便、快捷,可作为老年患者急性呼吸困难病因鉴别的一个重要检查方法 .%Objective To investigate the value of brain natriuretic peptide (BNP) in differentiating acute dyspnea from aged pa-tients with heart failure. Methods The concentration of plasma BNP was measured with immunofluorescence assay in 145 aged patients with dyspnea who admitted to hospital by emergency or were out - patients. Results The BNP level in patients with dyspnea caused by heart failure was significantly higher than that of lung disease patients. BNP for the diagnosis of left heart failure had a very strong predic-tive value, while the early diagnosis of pulmonary heart disease and right heart failure has yet to be explored. BNP values > 100ng / L for differentiating of heart failure was the following: the sensitivity of diagnosis was 94.1%, accuracy 93. I%, specificity 79.5%, positive predictive value was 91.3%, and negative predictive value was 85.4%. Conclusion BNP assay was a convenient, rapid and sensitive method for differentiating diagnosis in aged patients with heart failure, especially with left heart failure. It can be used as an important dif-ferential method in elderly patients with acute dyspnea.

  18. Significance of plasma brain natriuretic peptide in differentiating chronic cor pnlmonale from hypertensive heart failure%血浆脑钠素在肺源性心脏病和高血压性心脏病心力衰竭患者中的比较

    Institute of Scientific and Technical Information of China (English)

    黄蓓洁; 罗艳蓉; 徐晓雯; 李海玲

    2008-01-01

    Objective To study the significance of plasma brain natriuretic peptide(BNP)in differentiating patients with chronic cor pulmonale from those with hypertensive heart failure.Methods Thirty cases of cor pulmonale and 30 of hypertensive heart disease were recruited for the study.Heart rate and arterial partial oxygen pressure(PaO2)were measured for them,as well as plasma level of BNP Was measured by rapid immunofluorescence quantitative analysis.with 30 normal healthy persons as controls.Results As compared with the control group.plasma level of BNP increased significantly in patients with chronic cor pulmonale and hypertensive heart failure(P<0.05),and that in those with hypertensive heart failure[(597±68)ng/L]Was significantly higher than that in those with cot pulmonale[(179±34)ng/L,P<0.05]. Conclusion Plasma level of BNP can be used as an indicator to differentiate cor pulmonale from hypertensive heart failure both with dyspnea.%目的 探讨测定血浆脑钠素水平对鉴别肺源性心脏病和高血压性心脏病所致心力衰竭的意义.方法 肺源性心脏病、高血压性心脏病患者各30例,测定平均心率和PaO2,通过快速免疫荧光定量分析法测定血浆脑钠素水平,与30名正常健康人进行比较和分析.结果 肺源性心脏病和高血压性心脏病两组患者在心力衰竭时血浆脑钠素水平均高于对照组(P<0.05),其中高血压性心脏病组脑钠素[(597±68)ng/L]明显高于肺源性心脏病组[(179±34)ng/ml,P<0.01].结论 肺源性心脏病和高血压性心脏病患者心力衰竭时均表现出呼吸困难,血浆脑钠素可以作为鉴别两者的指标之一.

  19. Study on correlation between brain natriuretic peptide and heart rate variability in patients with type 2 diabetes and left ventricular diastolic dysfunction%2型糖尿病伴左室舒张功能不全患者心率变异性与B型尿钠肽的相关性分析

    Institute of Scientific and Technical Information of China (English)

    杨燕华; 刘自爱; 黄庆宁; 黄虔

    2013-01-01

    Objective To evaluate the correlation between he art rate variability and brain natriuretic peptide (BNP) in patients with type 2 diabetes and left ventricular diastolic dysfunction.Methods 100 patients with type 2 diabetes were included,all the patients' BNP level were over 100 pg/ml.SDNN-Index,RMSSD,PNN50 and BNP were measured,data were presented as (M ± SD).The correlation between heart rate variability and BNP level was assessed by Pearson Correlation Analysis (SPSS software).Results The correlation coefficient between SDNN-Index [(46.41 ± 17.74) ms] and BNP level was-0.472 (P < 0.01);The correlation coefficient between RMSSD [(37.18 ± 19.07) ms] and BNP level was-0.434 (P < 0.01); the correlation coefficient between PNN50[(18.88 ± 15.21)%] and BNP level was-0.589 (P < 0.01).Conclusion The heart rate variability in patients with type 2 diabetes and left ventricular diastolic dysfunction is obviously lower than that of normal people,and significantly correlated with BNP level.%目的 分析2型糖尿病伴左室舒张功能不全患者心率变异性与B型尿钠肽的关系.方法 收集100例B型尿钠肽≥100 pg/ml的2型糖尿病患者,研究其心率变异性与B型尿钠肽的相关性.心率变异性指标包括:SDNN-Index、RMSSD、PNN50,数据以平均值±标准差(M±SD)表示,用SPSS软件进行Pearson相关分析.结果 100例2型糖尿病伴心脏舒张功能不全患者SDNN-Index为(46.41±17.74) ms,RMSSD为(37.18±19.07) ms,PNN50为(18.88±15.21)%,SDNN-Index、RMSSD、PNN50与B型尿钠肽相关系数分别为-0.472、-0.434、-0.589,P均<0.01.结论 2型糖尿病伴心脏舒张功能不全患者的心率变异性明显低于正常人,且与B型尿钠肽水平相关.

  20. Endogenous Opioid Peptides and Epilepsy: Quieting the Seizing Brain?

    Science.gov (United States)

    1988-08-01

    observed to progressively decline endogenous ligand at the receptor be due to the syndrome of ’failing in terms of severity and duration, is unknown, to see...Grupper D., Can we consider that the focal and 12 tHenriksen, S. J., Wiesner, 1. B. and Tyano, S. and Laron . Z. (1987) Psycho- generalized depolarization

  1. Plasma brain natriuretic peptide levels in COPD without pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Ahmed G. El Gazzar

    2017-01-01

    Conclusion: Plasma BNP can be used as a useful prognostic biomarker of COPD and a good predictor of exacerbation, As BNP level was significantly higher in COPD patients than in control groups, (p < 0.005 and also significantly higher in grade (IV, III than grade (II and was significantly higher in grade (II than grade (I COPD patients, BNP level significantly higher (p < 0.005 during exacerbation than during remission of COPD patients.

  2. Potential of phage-displayed peptide library technology to identify functional targeting peptides

    Science.gov (United States)

    Krumpe, Lauren RH; Mori, Toshiyuki

    2010-01-01

    Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo. PMID:20150977

  3. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Science.gov (United States)

    Noli, Barbara; Brancia, Carla; Pilleri, Roberta; D'Amato, Filomena; Messana, Irene; Manconi, Barbara; Ebling, Francis J P; Ferri, Gian-Luca; Cocco, Cristina

    2015-01-01

    VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA) coupled with high-performance liquid (HPLC) or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.

  4. Natriuretic peptides: a new lipolytic pathway in human adipocytes.

    Science.gov (United States)

    Sengenès, C; Berlan, M; De Glisezinski, I; Lafontan, M; Galitzky, J

    2000-07-01

    Atrial natriuretic peptide (ANP) receptors have been described on rodent adipocytes and expression of their mRNA is found in human adipose tissue. However, no biological effects associated with the stimulation of these receptors have been reported in this tissue. A putative lipolytic effect of natriuretic peptides was investigated in human adipose tissue. On isolated fat cells, ANP and brain natriuretic peptide (BNP) stimulated lipolysis as much as isoproterenol, a nonselective beta-adrenergic receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest lipolytic effect. In situ microdialysis experiments confirmed the potent lipolytic effect of ANP in abdominal s.c. adipose tissue of healthy subjects. A high level of ANP binding sites was identified in human adipocytes. The potency order defined in lipolysis (ANP > BNP > CNP) and the ANP-induced cGMP production sustained the presence of type A natriuretic peptide receptor in human fat cells. Activation or inhibition of cGMP-inhibited phosphodiesterase (PDE-3B) (using insulin and OPC 3911, respectively) did not modify ANP-induced lipolysis whereas the isoproterenol effect was decreased or increased. Moreover, inhibition of adenylyl cyclase activity (using a mixture of alpha(2)-adrenergic and adenosine A1 agonists receptors) did not change ANP- but suppressed isoproterenol-induced lipolysis. The noninvolvement of the PDE-3B was finally confirmed by measuring its activity under ANP stimulation. Thus, we demonstrate that natriuretic peptides are a new pathway controlling human adipose tissue lipolysis operating via a cGMP-dependent pathway that does not involve PDE-3B inhibition and cAMP production.

  5. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Directory of Open Access Journals (Sweden)

    Barbara Noli

    Full Text Available VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA coupled with high-performance liquid (HPLC or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.

  6. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  7. Assessment of blood N-terminal pro-brain natriuretic peptide levels in patients with heart failure with preserved ejection fraction%射血分数正常的心力衰竭患者全血N-末端脑钠肽前体浓度变化

    Institute of Scientific and Technical Information of China (English)

    陈广胜; 徐崇利; 张郁青; 林涛

    2012-01-01

    Objectives To assess ihe changes of blood N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels in patients with heart failure with preserved ejection fraction (HFPEF). Methods Totally 78 patients with cardiovascular diseases were classified into three groups: 22 cases with normal heart function, 33 cases with HFPEF and 23 cases with heart failure with reduced ejection fraction (HFREF). Blood NT-pro-BNP levels were measured and echoeardiograms were performed in all patients. Results Blood NT-pro-BNP levels in patients with HFPEF were significantly higher than those in patients with normal heart function [(1 424+996 )pg/mL vs. (167+ 117 )pg/mL,P<0.01 ] and significantly lower than those in patients with HFREF [(1 424±996)mg/L vs. (5 910±2828)mg/L,P<0.01 ]. For heart failure patients, blood NT-pro-BNP levels were negatively correlated with ejection fraction (r=—0.72,P<0.01 ), positively correlated with left atrial diameter (r=0.34,-P<0.05), left end-diastolic ventricular diameter (r=0.61 ,P<0.05) , left end-systolic ventricular diameter (r=0.62,P<0.05) and E/A ratio (r=0.40, P<0.05). Conclusions Compared with that of HFREF, HFPEF is associated with a less elevated level of NT-pro-BNP.%目的 评估射血分数正常的心力衰竭(心衰)患者全血N-末端脑钠肽前休(N-terminal pro-brain natriureticpeptide,NT-pro-BNP)浓度的变化.方法 入选78例心脏病患者分为3组:心功能正常组22例,射血分数正常心衰(heart failure with preserved ejection fretion,HFPEF)组33例,射血分数减低心衰(heart failure with reduced ejection fraction,HFREF)组23例.测定患者的全血NT-pro-BNP浓度并进行超声心动图检查.结果 HFPEF组患者全血NT-proBNP浓度高于心功能正常组[(1 424±996)pg/mL vs.(167±117) pg/mL,P<0.01],低于HFREF组[(1 424±996)mg/L vs.(5 910±2 828)mg/L,P<0.01],差异有统计学意义.心衰患者全血NT-proBNP浓度与射血分数呈负相关(r=-0.72,P<0.01),与左心房内径(r=0.34,P<0.05)

  8. Peptide primary messengers in plants

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The peptide primary messengers regulate embryonic development,cell growth and many other activities in animal cells. But recent evidence verified that peptide primary messengers are also involved in plant defense responses, the recognition between pollen and stigma and keep the balance between cell proliferation and differentiations in shoot apical meristems. Those results suggest that plants may actually make wide use of peptide primary messengers, both in embryonic development and late life when they rally their cells to defend against pathogens and insect pests. The recent advance in those aspects is reviewed.

  9. Next generation natriuretic peptide measurement

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Goetze, Jens P

    2012-01-01

    Plasma measurement of natriuretic peptides is a "must" for clinical laboratories. For the next generation measurement, the unraveling of the molecular complexity of the peptides points toward a more qualitative assessment, as the posttranslational processing also changes with disease. Changes...... in the molecular heterogeneity could in itself contain valuable information of clinical status, and the time seems right for industry and dedicated researchers in the field to get together and discuss the next generation natriuretic peptide measurement. In such an environment, new strategies can be developed...

  10. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming;

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...... to haemodynamic changes in the pro-peptides copeptin, proadrenomedullin and pro-atrial natriuretic peptide (proANP) in patients with cirrhosis. MATERIALS AND METHODS: Fifty-four cirrhotic patients and 15 controls were characterized haemodynamically during a liver vein catheterization. Copeptin, proadrenomedullin...... found no extraction of copeptin, proadrenomedullin or proANP over the liver. Copeptin correlated with portal pressure (R=0·50, P

  11. Targeting the Eph System with Peptides and Peptide Conjugates.

    Science.gov (United States)

    Riedl, Stefan J; Pasquale, Elena B

    2015-01-01

    Eph receptor tyrosine kinases and ephrin ligands constitute an important cell communication system that controls development, tissue homeostasis and many pathological processes. Various Eph receptors/ephrins are present in essentially all cell types and their expression is often dysregulated by injury and disease. Thus, the 14 Eph receptors are attracting increasing attention as a major class of potential drug targets. In particular, agents that bind to the extracellular ephrin-binding pocket of these receptors show promise for medical applications. This pocket comprises a broad and shallow groove surrounded by several flexible loops, which makes peptides particularly suitable to target it with high affinity and selectivity. Accordingly, a number of peptides that bind to Eph receptors with micromolar affinity have been identified using phage display and other approaches. These peptides are generally antagonists that inhibit ephrin binding and Eph receptor/ ephrin signaling, but some are agonists mimicking ephrin-induced Eph receptor activation. Importantly, some of the peptides are exquisitely selective for single Eph receptors. Most identified peptides are linear, but recently the considerable advantages of cyclic scaffolds have been recognized, particularly in light of potential optimization towards drug leads. To date, peptide improvements have yielded derivatives with low nanomolar Eph receptor binding affinity, high resistance to plasma proteases and/or long in vivo half-life, exemplifying the merits of peptides for Eph receptor targeting. Besides their modulation of Eph receptor/ephrin function, peptides can also serve to deliver conjugated imaging and therapeutic agents or various types of nanoparticles to tumors and other diseased tissues presenting target Eph receptors.

  12. Apelin-13 as a novel target for intervention in secondary injury after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hai-jun Bao

    2016-01-01

    Full Text Available The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect

  13. Purification and characterization of bioactive peptides RYamide and CCHamide in the kuruma shrimp Marsupenaeus japonicus.

    Science.gov (United States)

    Mekata, Tohru; Kono, Tomoya; Satoh, Jun; Yoshida, Morikatsu; Mori, Kenji; Sato, Takahiro; Miyazato, Mikiya; Ida, Takanori

    2017-01-04

    To understand the regulation systems of appetite, bioactive peptides from the kuruma shrimp Marsupenaeus japonicus (Mj) were isolated and purified by reverse pharmacological assays using CHO cells expressing the Drosophila melanogaster G-protein-coupled receptors (GPCRs) CG5811 (a RYamide receptor) or CG14593 (a CCHamide-2 receptor). Four peptides having binding activity to GPCRs were obtained and named Mj RYamide-1, Mj RYamide-2, Mj RYamide-3, and Mj CCHamide. Genes encoding the prepropeptides of these peptides were identified using kuruma shrimp transcriptome databases. The Mj prepro-RYamide gene encodes a 130-amino acid polypeptide containing Mj RYamide-1, Mj RYamide-2, and Mj RYamide-3, whereas the Mj prepro-CCHamide gene encodes a 119-amino acid polypeptide containing a single Mj CCHamide peptide. The expression of these genes was confirmed in various neuronal organs including the brain and ventral nerve cord. In addition, prepro-RYamide gene expression is significantly reduced in the brain after starvation. RYamides may thus be associated with regulation of feeding or digestion. Changes in kayak (the c-fos ortholog in invertebrates) gene expression after administration of synthetic peptides were also investigated. Mj kayak expression levels are upregulated in hepatopancreas after treatment with Mj RYamide-3 or CCHamide. Thus, the peptides isolated in this study may have some regulatory effect on cellular metabolism in aquacultured invertebrates.

  14. Screening of TACE Peptide Inhibitors from Phage Display Peptide Library

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To obtain the recombinant tumor necrosis factor-α converting enzyme (TACE) ectodomain and use it as a selective molecule for the screening of TACE peptide inhibitors, the cDNA coding catalytic domain (T800) and full-length ectodomain (T1300) of TACE were amplified by RTPCR, and the expression plasmids were constructed by inserting T800 and T1300 into plasmid pET28a and pET-28c respectively. The recombinant T800 and T1300 were induced by IPTG, and SDSPAGE and Western blotting analysis results revealed that T800 and T1300 were highly expressed in the form of inclusion body. After Ni2+-NTA resin affinity chromatography, the recombinant proteins were used in the screening of TACE-binding peptides from phage display peptide library respectively. After 4 rounds of biopanning, the positive phage clones were analyzed by ELISA, competitive inhibition assay and DNA sequencing. A common amino acid sequence (TRWLVYFSRPYLVAT) was found and synthesized. The synthetic peptide could inhibit the TNF-α release from LPS-stimulated human peripheral blood mononuclear cells (PBMC) up to 60.3 %. FACS analysis revealed that the peptide mediated the accumulation of TNF-α on the cell surface. These results demonstrate that the TACE-binding peptide is an effective antagonist of TACE.

  15. Brain death.

    Science.gov (United States)

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  16. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    on a novel three-step procedure that identifies any reactive viral O-glycosyl peptide epitope with respect to (i) relevant peptide sequence, (ii) the reactive glycoform out of several possible glycopeptide isomers of that peptide sequence, and (iii) possibly tolerated carbohydrate or peptide structural...

  17. Central nervous system action of peptides to influence gastrointestinal motor function.

    Science.gov (United States)

    Taché, Y; Garrick, T; Raybould, H

    1990-02-01

    The central action of peptides to influence GI motility in experimental animals is summarized in Table 1. TRH stimulates gastric, intestinal, and colonic contractility in rats and in several experimental species. A number of peptides including calcitonin, CGRP, neurotensin, NPY, and mu opioid peptides act centrally to induce a fasted MMC pattern of intestinal motility in fed animals while GRF and substance P shorten its duration. The dorsal vagal complex is site of action for TRH-, bombesin-, and somatostatin-induced stimulation of gastric contractility, and for CCK-, oxytocin- and substance P-induced decrease in gastric contractions or intraluminal pressure. The mechanisms through which TRH, bombesin, calcitonin, neurotensin, CCK, and oxytocin alter GI motility are vagally mediated. An involvement of central peptidergic neurons in the regulation of gut motility has recently been demonstrated in Aplysia, indicating that such regulatory mechanisms are important in the phylogenesis. Alterations of the pattern of GI motor activity are associated with functional changes in transit. TRH is so far the only centrally acting peptide stimulating simultaneously gastric, intestinal, and colonic transit in various animals species. Opioid peptides acting on mu receptor subtypes in the brain exert the opposite effect and inhibit concomitantly gastric, intestinal, and colonic transit. Bombesin and CRF were found to act centrally to inhibit gastric and intestinal transit and to stimulate colonic transit in the rat. The antitransit effect of calcitonin and CGRP is limited to the stomach and small intestine. The delay in GI transit is associated with reduced GI contractility for most of the peptides except central bombesin that increases GI motility. Nothing is known about brain sites through which these peptides act to alter gastric emptying and colonic transit. Regarding brain sites influencing intestinal transit, TRH-induced stimulation of intestinal transit in the rat is

  18. Effect of injecting brain cell growth peptide into conduit at the anastomose end of autogenous vein graft conduit on functional rehabilitation of facial nerve injury%自体静脉套吻合端套管内注入脑细胞生长肽对面神经损伤功能恢复的作用

    Institute of Scientific and Technical Information of China (English)

    韩思源; 宋涛; 王玉新

    2004-01-01

    背景:面神经损伤后功能恢复需要较长时间,如何加速面神经的功能恢复是该领域正在研究的课题.目的:比较面神经损伤修复的不同方法,探讨自体静脉套接吻合口及脑细胞生长肽在临床上修复面神经损伤的效果.设计:以诊断为依据的病例对照研究.地点和对象:中国医科大学附属第一医院1999-01/2001-12收治44例面神经损伤患者和1999-01以前收治面神经损伤患者30例.干预:对44例创伤后和腮腺区恶性肿瘤切除造成的面神经损伤患者,在手术显微镜下行神经断端对位吻合,将自体静脉管套入吻合口并在管套内注入脑细胞生长肽.对30例面神经损伤患者采用传统神经端吻合法修复,术后不同时间观察面部表情肌功能恢复及肌电图的动态变化.主要观察指标:观察面部表情肌功能恢复的时间,检测面神经传导速度的动态变化.结果:30例创伤性面神经损伤患者,功能恢复最快9周,最迟13周,平均(11.1±1.1)周,与传统方法(25.8±1.8)周比较有显著性差异(t=34.875,P<0.01);14例肿瘤切除面神经立即修复的患者,功能恢复最快13周,最迟15周,平均(13.8±0.8)周,与传统方法(34.8±2.9)周比较有显著性差异(t=26.336,P<0.01).肌电图检测面神经传导速度的恢复呈递增趋势,表情肌功能恢复时两种方法传导速度比较无显著性差异(P>0.05).结论:自体静脉管套入吻合口并注入脑细胞生长肽的方法均比传统方法效果显著,是一种临床效果比较突出的面神经损伤修复方法.%BACKGROUND: Functional rehabilitation requires longer time after facial nerve injury. How to speed up the functional rehabilitation of facial nerve is a topic in this academic field.OBJECTIVE: To discuss the effect of autogenous vein graft conduit anastomose and brain cell growth peptide(BCGP) on clinical rehabilitation of facial nerve injury by comparing different methods in the rehabilitation of facial

  19. Short-term prognosis evaluation of plasma brain natriuretic peptide concentration on the non-diabetic acute myocardial infarction patients with stress hyperglycemia%血浆脑钠肽水平对非糖尿病急性心肌梗死并发应激性高血糖患者近期预后评价

    Institute of Scientific and Technical Information of China (English)

    李永东; 董春花; 刘丹

    2012-01-01

    目的:观察非糖尿病急性心肌梗死(AMI)并发应激性高血糖患者血浆脑钠肽(BNP)水平变化,探讨血浆BNP在非糖尿病AMI并发应激性高血糖患者近期预后评估中的作用.方法:将60例AMI患者根据空腹血糖值分为2组,非糖尿病AMI并发应激性高血糖组(试验组)(血糖≥7.0 mmol/L) 36例,AMI未并发应激性高血糖组(对照组)(血糖<7.0 mmol/L)24例,对AMI患者在发病后24 h时测定血浆BNP水平.所有入选患者入院后2周行心脏彩超检查,测定和计算左室舒张末期内径(LVDd)、左室收缩末期内径(LVSd)、左室射血分数(LVEF);同时行24 h动态心电图检测,记录2组患者心律失常发生率;并观察住院2周内心绞痛、心力衰竭、心源性休克、心源性猝死等主要不良心血管事件(MACE)发生率.结果:①发病后24 h血浆BNP浓度试验组明显高于对照组[(671.87±631.71)ng/L∶(299.53±455.67)ng/L,P<0.01].②试验组LVDd、LVSd均高于对照组[(53.01±4.00)mm∶(50.50±3.20)mm,(45.32±5.92)mm∶ (42.52±3.27)mm,均P<0.05],LVEF低于对照组[(52.86±5.79)%∶(61.00±7.54)%,P<0.05].③试验组室性心律失常、室上性心律失常、严重窦性心动过缓和房室传导阻滞发生率均高于对照组(分别为66.67%∶41.67%,63.89%∶37.50%,47.22%∶20.83%,均P<0.05).④试验组与对照组住院2周内MACE发生率,包括心力衰竭(36.11%∶ 12.50%)、心源性休克(16.67%∶0.00%)、梗死后心绞痛(25.00%∶4.17%)均差异有统计学意义(均P<0.05);死亡率(2.78%∶0.00%)差异无统计学意义(P>0.05).结论:非糖尿病AMI并发应激性高血糖患者近期预后差,血浆BNP水平升高更为明显.%Objective:To observe the change of plasma brain natriuretic peptide concentration in the non-diabetic acute myocardial infarction patients with stress hyperglycemia, and to study its role in prognosis evaluation. Method:Sixty patients with acute myocardial

  20. A new strategy for specific imaging of neural cells based on peptide-conjugated gold nanoclusters

    Directory of Open Access Journals (Sweden)

    Zhang E

    2015-03-01

    Full Text Available Enqi Zhang, Ailing Fu School of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China Abstract: Despite the significant progress in molecular imaging technologies that has been made in recent years, the specific detection of neural cells still remains challenging. Here, we suggest the use of gold nanoclusters (AuNCs modified with a brain-targeting peptide as a potential imaging candidate for detecting neural cells in vitro and in mice. AuNCs of less than 10 nm (dynamic light scattering analysis were first prepared using the “green” synthetic approach, and then a targeting peptide, rabies virus glycoprotein derived peptide (RDP, was conjugated to the AuNCs for improving the efficiency and specificity of neural cell penetration. The conjugate’s mechanism of cellular attachment and entry into neural cells was suggested to be receptor-mediated endocytosis through clathrin-coated pits. Also, noninvasive imaging analysis and animal studies indicated that the RDP-modified nanoclusters could concentrate in the brain and locate in neural cells. This study suggests the feasibility of using targeting peptide-modified nanoclusters for noninvasive imaging brain cells in vivo. Keywords: RDP, targeted delivery, bioimaging, brain 

  1. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    The alarming increase in the prevalence of obesity and associated comorbidities such as type 2 diabetes emphasizes the urgent need for new drugs with both anorectic and antidiabetic eects. Several peptide hormones secreted from the gastrointestinal tract play an important role in the physiological...... regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs...... of food intake, which was enhanced compared to native NMU. Project II explored the design, synthesis, and characterization of neoglycolipidated analogs of glucagon-like peptide 1 (GLP-1). Neoglycolipidation reduced lipophilicity and maintained or even improved in vitro potency towards the GLP-1 receptor...

  2. Brain computer

    Directory of Open Access Journals (Sweden)

    Sarah N. Abdulkader

    2015-07-01

    Full Text Available Brain computer interface technology represents a highly growing field of research with application systems. Its contributions in medical fields range from prevention to neuronal rehabilitation for serious injuries. Mind reading and remote communication have their unique fingerprint in numerous fields such as educational, self-regulation, production, marketing, security as well as games and entertainment. It creates a mutual understanding between users and the surrounding systems. This paper shows the application areas that could benefit from brain waves in facilitating or achieving their goals. We also discuss major usability and technical challenges that face brain signals utilization in various components of BCI system. Different solutions that aim to limit and decrease their effects have also been reviewed.

  3. Peptides and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bachovchin, W.W.; Unkefer, C.J.

    1994-12-01

    Advances in magnetic resonance and vibrational spectroscopy make it possible to derive detailed structural information about biomolecular structures in solution. These techniques are critically dependent on the availability of labeled compounds. For example, NMR techniques used today to derive peptide and protein structures require uniformity {sup 13}C-and {sup 15}N-labeled samples that are derived biosynthetically from (U-6-{sup 13}C) glucose. These experiments are possible now because, during the 1970s, the National Stable Isotope Resource developed algal methods for producing (U-6-{sup 13}C) glucose. If NMR techniques are to be used to study larger proteins, we will need sophisticated labelling patterns in amino acids that employ a combination of {sup 2}H, {sup 13}C, and {sup 15}N labeling. The availability of these specifically labeled amino acids requires a renewed investment in new methods for chemical synthesis of labeled amino acids. The development of new magnetic resonance or vibrational techniques to elucidate biomolecular structure will be seriously impeded if we do not see rapid progress in labeling technology. Investment in labeling chemistry is as important as investment in the development of advanced spectroscopic tools.

  4. Antimicrobial peptides in crustaceans

    Directory of Open Access Journals (Sweden)

    RD Rosa

    2010-11-01

    Full Text Available Crustaceans are a large and diverse invertebrate animal group that mounts a complex and efficient innate immune response against a variety of microorganisms. The crustacean immune system is primarily related to cellular responses and the production and release of important immune effectors into the hemolymph. Antimicrobial proteins and/or peptides (AMPs are key components of innate immunity and are widespread in nature, from bacteria to vertebrate animals. In crustaceans, 15 distinct AMP families are currently recognized, although the great majority (14 families comes from members of the order Decapoda. Crustacean AMPs are generally cationic, gene-encoded molecules that are mainly produced by circulating immune-competent cells (hemocytes or are derived from unrelated proteins primarily involved in other biological functions. In this review, we tentatively classified the crustacean AMPs into four main groups based on their amino acid composition, structural features and multi-functionality. We also attempted to summarize the current knowledge on their implication both in an efficient response to microbial infections and in crustacean survival.

  5. Antimicrobial peptides in annelids

    Directory of Open Access Journals (Sweden)

    A Tasiemski

    2008-06-01

    Full Text Available Gene encoded antimicrobial peptides (AMPs are widely distributed among living organisms including plants, invertebrates and vertebrates. They constitute important effectors of the innate immune response by exerting multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis and immune induction. In invertebrates, most of the data describe the characterization and/or the function of AMPs in the numerically and economically most representative group which are arthropods. Annelids are among the first coelomates and are therefore of special phylogenetic interest. Compared to other invertebrate groups, data on annelid’s immunity reveal heavier emphasis on the cellular than on the humoral response suggesting that immune defense of annelids seems to be principally developed as cellular immunity.This paper gives an overview of the variety of AMPs identified in the three classes of annelids, i.e. polychaetes, oligochaetes and achaetes. Their functions, when they have been studied, in the humoral or cellular response of annelids are also mentioned.

  6. Natriuretic peptides in cardiometabolic regulation and disease

    DEFF Research Database (Denmark)

    Zois, Nora E; Bartels, Emil D; Hunter, Ingrid

    2014-01-01

    decade. Dysregulation of the natriuretic peptide system has been associated with obesity, glucose intolerance, type 2 diabetes mellitus, and essential hypertension. Moreover, the natriuretic peptides have been implicated in the protection against atherosclerosis, thrombosis, and myocardial ischaemia. All...... these conditions can coexist and potentially lead to heart failure, a syndrome associated with a functional natriuretic peptide deficiency despite high circulating concentrations of immunoreactive peptides. Therefore, dysregulation of the natriuretic peptide system, a 'natriuretic handicap', might be an important...

  7. Pharmacokinetic properties of tandem d-peptides designed for treatment of Alzheimer's disease.

    Science.gov (United States)

    Leithold, Leonie H E; Jiang, Nan; Post, Julia; Niemietz, Nicole; Schartmann, Elena; Ziehm, Tamar; Kutzsche, Janine; Shah, N Jon; Breitkreutz, Jörg; Langen, Karl-Josef; Willuweit, Antje; Willbold, Dieter

    2016-06-30

    Peptides are more and more considered for the development of drug candidates. However, they frequently exhibit severe disadvantages such as instability and unfavourable pharmacokinetic properties. Many peptides are rapidly cleared from the organism and oral bioavailabilities as well as in vivo half-lives often remain low. In contrast, some peptides consisting solely of d-enantiomeric amino acid residues were shown to combine promising therapeutic properties with high proteolytic stability and enhanced pharmacokinetic parameters. Recently, we have shown that D3 and RD2 have highly advantageous pharmacokinetic properties. Especially D3 has already proven promising properties suitable for treatment of Alzheimer's disease. Here, we analyse the pharmacokinetic profiles of D3D3 and RD2D3, which are head-to-tail tandem d-peptides built of D3 and its derivative RD2. Both D3D3 and RD2D3 show proteolytic stability in mouse plasma and organ homogenates for at least 24h and in murine and human liver microsomes for 4h. Notwithstanding their high affinity to plasma proteins, both peptides are taken up into the brain following i.v. as well as i.p. administration. Although both peptides contain identical d-amino acid residues, they are arranged in a different sequence order and the peptides show differences in pharmacokinetic properties. After i.p. administration RD2D3 exhibits lower plasma clearance and higher bioavailability than D3D3. We therefore concluded that the amino acid sequence of RD2 leads to more favourable pharmacokinetic properties within the tandem peptide, which underlines the importance of particular sequence motifs, even in short peptides, for the design of further therapeutic d-peptides.

  8. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets.

    Science.gov (United States)

    Giordano, Carmela; Marchiò, Maddalena; Timofeeva, Elena; Biagini, Giuseppe

    2014-01-01

    Various ketogenic diet (KD) therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine) and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin, and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs). In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the neurohormonal

  9. Silicon Brains

    Science.gov (United States)

    Hoefflinger, Bernd

    Beyond the digital neural networks of Chap. 16, the more radical mapping of brain-like structures and processes into VLSI substrates has been pioneered by Carver Mead more than 30 years ago [1]. The basic idea was to exploit the massive parallelism of such circuits and to create low-power and fault-tolerant information-processing systems. Neuromorphic engineering has recently seen a revival with the availability of deep-submicron CMOS technology, which allows for the construction of very-large-scale mixed-signal systems combining local analog processing in neuronal cells with binary signalling via action potentials. Modern implementations are able to reach the complexity-scale of large functional units of the human brain, and they feature the ability to learn by plasticity mechanisms found in neuroscience. Combined with high-performance programmable logic and elaborate software tools, such systems are currently evolving into user-configurable non-von-Neumann computing systems, which can be used to implement and test novel computational paradigms. The chapter introduces basic properties of biological brains with up to 200 Billion neurons and their 1014 synapses, where action on a synapse takes ˜10 ms and involves an energy of ˜10 fJ. We outline 10x programs on neuromorphic electronic systems in Europe and the USA, which are intended to integrate 108 neurons and 1012 synapses, the level of a cat's brain, in a volume of 1 L and with a power dissipation design an intelligent technical response.

  10. Robot brains

    NARCIS (Netherlands)

    Babuska, R.

    2011-01-01

    The brain hosts complex networks of neurons that are responsible for behavior in humans and animals that we generally call intelligent. I is not easy to give an exact definition of intelligence – for the purpose of this talk it will suffice to say that we refer to intelligence as a collection of cap

  11. Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers

    Science.gov (United States)

    Anand, Prachi; O'Neil, Alison; Lin, Emily; Douglas, Trevor; Holford, Mandë

    2015-08-01

    The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.

  12. Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

    Science.gov (United States)

    Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

    2016-01-01

    This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.

  13. Differences in the Central Anorectic Effects of Glucagon-Like Peptide-1 and Exendin-4 in Rats

    OpenAIRE

    Barrera, Jason G.; D'Alessio, David A.; Drucker, Daniel J.; Woods, Stephen C.; Seeley, Randy J

    2009-01-01

    OBJECTIVE Glucagon-like peptide (GLP)-1 is a regulatory peptide synthesized in the gut and the brain that plays an important role in the regulation of food intake. Both GLP-1 and exendin (Ex)-4, a long-acting GLP-1 receptor (GLP-1r) agonist, reduce food intake when administered intracerebroventricularly, whereas Ex4 is much more potent at suppressing food intake when given peripherally. It has generally been hypothesized that this difference is due to the relative pharmacokinetic profiles of ...

  14. Versatile Peptide C-Terminal Functionalization via a Computationally Engineered Peptide Amidase

    NARCIS (Netherlands)

    Wu, Bian; Wijma, Hein J.; Song, Lu; Rozeboom, Henriette J.; Poloni, Claudia; Tian, Yue; Arif, Muhammad I.; Nuijens, Timo; Quaedflieg, Peter J. L. M.; Szymanski, Wiktor; Feringa, Ben L.; Janssen, Dick B.

    2016-01-01

    The properties of synthetic peptides, including potency, stability, and bioavailability, are strongly influenced by modification of the peptide chain termini. Unfortunately, generally applicable methods for selective and mild C-terminal peptide functionalization are lacking. In this work, we explore

  15. DHPC strongly affects the structure and oligomerization propensity of Alzheimer's Aβ(1-40) peptide.

    Science.gov (United States)

    Dahse, Kirsten; Garvey, Megan; Kovermann, Michael; Vogel, Alexander; Balbach, Jochen; Fändrich, Marcus; Fahr, Alfred

    2010-11-05

    Alzheimer's disease (AD) is thought to depend on the deleterious action of amyloid fibrils or oligomers derived from β-amyloid (Aβ) peptide. Out of various known Aβ alloforms, the 40-residue peptide Aβ(1-40) occurs at highest concentrations inside the brains of AD patients. Its aggregation properties critically depend on lipids, and it was thus proposed that lipids could play a major role in AD. To better understand their possible effects on the structure of Aβ and on the ability of this peptide to form potentially detrimental amyloid structures, we here analyze the interactions between Aβ(1-40) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). DHPC has served, due to its controlled properties, as a major model system for studying general lipid properties. Here, we show that DHPC concentrations of 8 mM or higher exert dramatic effects on the conformation of soluble Aβ(1-40) peptide and induce the formation of β-sheet structure at high levels. By contrast, we find that DHPC concentrations well below the critical micelle concentration present no discernible effect on the conformation of soluble Aβ, although they substantially affect the peptide's oligomerization and fibrillation kinetics. These data imply that subtle lipid-peptide interactions suffice in controlling the overall aggregation properties and drastically accelerate, or delay, the fibrillation kinetics of Aβ peptide in near-physiological buffer solutions.

  16. Successful adjuvant-free vaccination of BALB/c mice with mutated amyloid β peptides

    Directory of Open Access Journals (Sweden)

    Wahi Monika M

    2008-02-01

    Full Text Available Abstract Background A recent human clinical trial of an Alzheimer's disease (AD vaccine using amyloid beta (Aβ 1–42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Aβ peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine. Results All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Aβ in APP/PS1 transgenic mouse brain tissue. Conclusion Our study demonstrated that an adjuvant-free vaccine with different Aβ peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Aβ peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.

  17. Automated solid-phase peptide synthesis to obtain therapeutic peptides

    Directory of Open Access Journals (Sweden)

    Veronika Mäde

    2014-05-01

    Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

  18. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  19. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  20. Brain Tumors (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  1. 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 ...

  2. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk

    2009-07-01

    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  3. Exploration of the Medicinal Peptide Space.

    Science.gov (United States)

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

  4. Perspectives and Peptides of the Next Generation

    Science.gov (United States)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  5. Organisation and functional role of the brain angiotensin system

    Directory of Open Access Journals (Sweden)

    Catherine Llorens-Cortes

    2002-03-01

    Full Text Available The discovery that all components of the renin-angiotensin system (RAS are present in the brain led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurones have been visualised in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular and supraoptic nuclei, and a second pathway connecting the hypothalamus to the medulla oblongata. Blood-brain-barrier deficient circumventricular organs are rich in angiotensin II (Ang II receptors. By activating these receptors, circulating Ang II may act on central cardiovascular centres via angiotensinergic neurones, providing a link between peripheral and central Ang II systems. Among the effector peptides of the brain RAS, Ang II and angiotensin III (Ang III have the same affinity for type 1 and type 2 Ang II receptors. When injected into the brain, both peptides increase blood pressure (BP, water intake and pituitary hormone release and may modify learning and memory. Since Ang II is converted in vivo to Ang III, the nature of the true effector is unknown. This review summarises new insights into the predominant role of brain Ang III in the control of BP and underlines the fact that brain aminopeptidase A, the enzyme forming central Ang III, could constitute a putative central therapeutic target for the treatment of hypertension.

  6. Peptide synthesis using unprotected peptides through orthogonal coupling methods.

    Science.gov (United States)

    Tam, J P; Lu, Y A; Liu, C F; Shao, J

    1995-01-01

    We describe an approach to the synthesis of peptides from segments bearing no protecting groups through an orthogonal coupling method to capture the acyl segment as a thioester that then undergoes an intramolecular acyl transfer to the amine component with formation of a peptide bond. Two orthogonal coupling methods to give the covalent ester intermediate were achieved by either a thiol-thioester exchange mediated by a trialkylphosphine and an alkylthiol or a thioesterification by C alpha-thiocarboxylic acid reacting with a beta-bromo amino acid. With this approach, unprotected segments ranging from 4 to 37 residues were coupled to aqueous solution to give free peptides up to 54 residues long with high efficiency. Images Fig. 1 PMID:8618926

  7. The Creative Brain.

    Science.gov (United States)

    Herrmann, Ned

    1982-01-01

    Outlines the differences between left-brain and right-brain functioning and between left-brain and right-brain dominant individuals, and concludes that creativity uses both halves of the brain. Discusses how both students and curriculum can become more "whole-brained." (Author/JM)

  8. Brain and Addiction

    Science.gov (United States)

    ... Search Term(s): Teens / Drug Facts / Brain and Addiction Brain and Addiction Print Your Brain Your brain is who you are. It’s what ... solve problems, and make decisions. How Does Your Brain Communicate? The brain is a complex communications network ...

  9. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  10. Twilight reloaded: the peptide experience

    Science.gov (United States)

    Weichenberger, Christian X.; Pozharski, Edwin; Rupp, Bernhard

    2017-01-01

    The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallo­graphic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein–peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided. PMID:28291756

  11. Clinical value of N-terminal pro-brain natriuretic peptide for evaluating acute heart failure in patients undergoing hemodialysis%前体脑钠肽对血液透析患者发生急性心功能不全的临床诊断价值

    Institute of Scientific and Technical Information of China (English)

    刘国望; 晏德华; 叶燕丽

    2012-01-01

    目的 在维持性血液透析患者中,研究前体脑钠肽(NT-proBNP)对评价急性心功能不全的临床价值.方法 检测113人次以呼吸困难就诊,临床上怀疑存在急性心功能不全的血液透析患者的NT-proBNP水平.根据定义的临床指标判断急性左心力衰竭.结果 急性心力衰竭组NT-proBNP水平高于非急性心力衰竭组.NT-proBNP和年龄、透析时间以及左心室厚度无关,和右心房大小正相关.对于急性心力衰竭的患者,NT-proBNP水平和心力衰竭临床分级呈正相关性(rs=0.526,P=0.012).多变量分析显示,NT-proBNP水平每升高100 pg/ml,急性心力衰竭的危险性增加2.01倍(OR 3.01,95% CI 2.11~3.85).经ROC曲线分析,NT-proBNP诊断急性心力衰竭的曲线下面积为0.819(95% CI 0.728~0.842).结论 对于血液透析患者,NT-proBNP能作为诊断急性心力衰竭的生物学标志物.%Objective To investigate the clinical value of N-terminal pro-brain natriuretic peptide( NT-proBNP )for evaluating acute heart failure in patients undergoing hemodialysis. Methods NT-proBNP levels of 113 hemodialysis cases were measured,who were hospitalized with tachypnea and were suspected to be with acute heart failure. The diagnosis of acute heart failure was made by the definition of the guideline for diagnosis and therapy of acute left heart failure. Results The level of NT-proBNP was higher in the patients with acute heart failure than those without. The level of NT-proBNP was not associated with age, dialysis time and thickness of left ventricle, whereas correlated with right atrium. The level of NT-proBNP in those with acute left heart failure was also related to class of clinical heart failure( rs = 0. 526, P =0.012 ). The level of NT-proBNP increased 100 pg/ml,the risk for acute heart failure increased 2 fold( odds ratio 3. 01,95% confidence interval 1. 11-3. 85 ). The area under ROC curve of the NT-proBNP for diagnosis of acute heart failure was 0.819(95% confidence

  12. Advantage study on utilization of N-terminal pro-B-brain natriuretic peptide for early diagnosis and therapeutic effect monitoring of acute coronary syndrome%N-端脑钠素前体应用于急性冠状动脉综合征早期诊断及疗效监控的优势性研究

    Institute of Scientific and Technical Information of China (English)

    唐敏儿

    2016-01-01

    Objective To explore clinical advantages of N‐terminal pro‐B‐brain natriuretic peptide(NT‐proBNP) in early diagno‐sis and therapeutic effect monitoring of acute coronary syndrome(ACS) .Methods A total of 97 cases of patients with chest pain and obvious discomfort who treated with coronary angiography in this hospital from February to December 2014 were selected .A‐mong these patients ,34 cases with non‐ACS were enrolled in the control group ,while other 63 cases with ACS were divided into the ST‐segment elevation myocardial infarction(STEM ) group ,non‐ST‐segment elevation myocardial infarction(NSTEM ) group and unstable angina pectoris(UA) group .The glycemia ,lipemia ,blood pressure and other indicators were observed .Results The levels of fasting blood‐glucose were within the normal reference interval in all groups ,while levels of lipemia ,plasma NT‐proBNP and blood pressure were higher than the upper limits of normal reference intervals ,and plasma levels of NT‐proBNP were higher than standard of good prognosis(NT‐proBNP0 .05) .The levels of lipemia and plasma NT‐proBNP and blood pressure were obviously decreased in patients with ACS at each treatment stage .Conclusion NT‐proBNP as a kind of myocardial marker has high accuracy in early diagnosis of ACS ,which could be applied in therapeutic effect monitoring and provide guidance for reasonable selection of treatment strategy .%目的:研究N‐端脑钠素前体(NT‐proBNP)在急性冠状动脉综合征(ACS)早期诊断及疗效监测中的临床优势。方法选取2014年2~12月因胸部疼痛或不适感明显在该院心内科就诊且行冠状动脉造影的患者97例,其中34例非ACS患者纳入对照组,63例ACS患者分别纳入ST段抬高型心肌梗死(STEM)组、非ST段抬高型心肌梗死(NSTEM)组、不稳定型心绞痛(UA)组。观察各组患者血糖、血脂、血压及NT‐proBNP等指标。结果各组患者空腹血糖均在

  13. 高血压病患者的血浆肾素活性与脑钠肽水平及预后的关系%Relationship between plasma renin activity,brain natriuretic peptide level,and prognosis in patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    马军; 蒋金法

    2014-01-01

    Objective To observe the difference of brain natriuretic peptide(BNP)level in hypertensive patients with various plasma renin activity,and to follow up the clinical outcome within 12 months. Methods Eight hundred and forty-five cases of new hypertensive patients as the research object. The patients on the same risk level were divided into high renin and low renin groups according by five points,the difference of BNP level between the two groups was compared,and cardiovascular events were followed up for 12 months. Results In low or moderate risk-patients with high blood pressure,plasma renin level difference had little impact on BNP concentration and clinical events. The differences of the renin activity among high-risk patients had a significant influence only on BNP level. The plasma BNP level and cardiovascular events (myocardial infarction,unstable angina,sudden cardiac death,heart failure,malignant arrhythmia,stroke) in high-rennin group were significantly higher than those in low-renin group. Conclusion Extremely high-risk hypertensive patients with high renin activity had higher BNP levels,which might participate in the target organ damage from hypertension,leading to more cardiovascular events.%目的:观察具有不同血浆肾素活性的高血压病患者中血清脑钠肽(BNP)水平的差异,并随访12个月内的临床转归情况。方法将845例新发高血压病患者作为研究对象,对同一危险分层的患者根据血浆肾素差异按5分位法分取高肾素组和低肾素组,比较两组血清BNP水平的差异,并随访12个月内心脑血管事件的发生情况。结果低、中危高血压患者中血清肾素水平差异对血浆BNP水平和临床事件的影响甚微;高危患者中肾素活性的差异仅对BNP的影响具有显著性;极高危患者的高肾素组,其血浆BNP浓度和心脑血管事件(心肌梗死、不稳定型心绞痛、心源性猝死、心力衰竭、恶性心律失常、脑卒中)

  14. 重组人脑利钠肽对急性心肌梗死后急性心力衰竭循环内分泌激素及左室功能的影响%Efficacy of recombinant human brain natriuretic peptide on endocrine hormone and left ventricular function of acute heart failure patients from acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    陈茂华; 薄小萍; 羊镇宇

    2012-01-01

    目的:了解重组人脑利钠肽(rhBNP)对急性心肌梗死(AMI)后急性失代偿性心力衰竭(HF)患者循环内分泌激素及左室功能的影响,并评判其临床疗效和安全性.方法:AMI并发急性失代偿性HF患者58例,随机分为rhBNP组26例和硝酸异山梨酯组32例,在标准抗缺血、抗HF治疗的基础上,持续静脉应用rhBNP或硝酸异山梨酯48 h,分别于治疗前和治疗后6h、24 h及72 h,检测血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)和醛固酮(ALD)浓度;治疗前及治疗后72 h测定血BNP、超声心动图测定左室舒张末期内径(LVDd)及左室射血分数(LVEF);同时比较30 d内主要不良心脏事件(MACE)的发生情况.结果:与硝酸异山梨酯组比较,rhBNP组血浆PRA、AngⅡ、ALD治疗6h后即降低(均P<0.05),72 h时仍保持较低水平(均P<0.01);治疗后72 hBNP下降(P<0.01),LVDd及LVEF明显改善(P<0.05,P<0.01),30 d MACE事件发生率rhBNP组显著低于硝酸异山梨酯组(P<0.05).结论:rhBNP对AMI伴HF患者的血浆肾素、AngⅡ和ALD水平有快速而持续的抑制作用,可以显著改善左室功能,同时降低30 d内MACE事件发生率.%Objective:To investigate the clinical efficacy of recombinant human brain natriuretic peptide (rhB-NP) on endocrine hormone and left ventricular function of acute decompensated heart failure (ADHF) patients resulted from acute myocardial infarcfion (AMI). Method: Fifty-eight patients with AMI-ADHF were randomly divided into rhBNP group (n = 26) and isosorbide mononitrate group (n=32). They were all received standard anti-ischemic and anti-heart failure treatment. We detected plasma renin activity (PRA) , angiotensin II (Ang E ) and aldosterone (ALD) concentration before treatment and after 6, 24 and 72 hours. Blood BNP, left ventricular end-diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were determined before treatment and after 72 hours. All patients were followed up for 1 month to record

  15. Correlation Analysis of CA125 and N-terminal pro-brain natriuretic peptide and cardiac function in patients with chronic heart failure%慢性心衰患者CA125与N-末端脑钠素原及心功能相关性研究

    Institute of Scientific and Technical Information of China (English)

    张建秀; 高华; 曹倩; 闫超

    2014-01-01

    目的:探讨慢性心衰患者血清肿瘤抗原糖类抗原125(C A 125)与N‐末端脑钠素原(WT‐‐ProBNP)及心功能相关性。方法:选择慢性心衰患者108例,根据NYHA 心功能分级标准进行分级,分别检测CA19‐9、CA125、NT‐ProBNP、E/E’及左心射血分数(LVEF)并检测LVEF及E/E’。结果:III级患者CA125、NT‐ProBNP较II级患者均出现显著性升高(P<0.05),IV级患者较II、III级患者均出现显著性升高(P<0.05)。III级患者LVEF、E/E’较II级患者均出现显著性差异(P<0.05),IV级患者LVEF较II级患者均出现显著性升高(P<0.05),E/E'较II、III级患者均出现显著性升高(P<0.05)。CA125与NT‐ProBNP、E/E'显著正相关(P<0.05),与LVEF显著负相关(P<0.05)。结论:CA125与心功能相关指标密切相关,对其水平检测有助于明确慢性心衰的进展。%Objective:To investigate correlation analysis of CA125 and N‐terminal pro‐brain natriuretic peptide and cardiac function in patients with chronic heart failure .Methods :108 patients with chronic heart failure were classified according to NYHA class grading standards ,CA19‐9 ,CA125 ,NT‐ProBNP ,E /E'and LVEF and detect LVEF and E /E'were detected .Results :In stage III patients CA125 ,NT‐ProBNP than stage II patients were significantly higher (P <0 .05) ,stage IV patients than stage II ,stage III patients were significantly higher (P <0 . 05) .LVEF ,E /E'in III patients compared with grade II patients were significantly different (P <0 .05) ,LVEF in grade IV was higher than that in grade II patients (P <0 .05) ,E /E'than grade II and grade III were significantly higher(P <0 .05) .CA125 and NT‐ProBNP ,E /E'showed significant positive correlation (P <0 .05) ,and LVEF was significantly negatively correlated (P <0 .05) .Conclusion:CA125 is closely related to heart function related in‐dicators ,which help to

  16. 围生期心肌病患者血清B型脑钠肽与超敏C反应蛋白水平变化及临床意义%The clinical significance of the level changes of B type brain natriuretic peptide and high sensitive C-reaction protein in peripartum cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    汪朝春; 杨群爱

    2013-01-01

    目的:探讨血清B型脑钠肽(BNP)与超敏C反应蛋白(hs- CRP)水平在围生期心肌病(PPCM)诊断及治疗中的价值。方法测定21例PPCM患者(观察组)BNP hs- CRP,同时行心脏彩色多普勒超声心动图检查测量左心室舒张末期内径(LVED)和左心室射血分数(LVEF),并对患者进行1个月的随访。选取同期住院的正常分娩患者20例作为对照组。结果观察组与对照组比较,BNP[(870.1±168.2)ng/L,(99.2±38.3)ng/L]、hs- CRP[(28.1±7.2)mg/L,(6.7±2.2)mg/L]明显升高(均P<0.01),hs- CRP与BNP呈正相关(r=0.67,P<0.01)。经过1个月治疗,观察组平均LVEF由(33.1±9.5)%提高至(50.3±12.1)%,BNP、hs- CRP[治疗后分别为(196.6±40.2)ng/L、(7.8±3.1)mg/L)]明显下降(均P<0.01)。结论 BNP及hs- CRP可以作为PPCM较好的诊断、治疗参考指标。%Objective To explore the clinical significances of the level changes of B type brain natriuretic peptide (BNP) and high sensitive C- reaction protein(hs- CRP) for diagnosis and treatment in peripartum cardiomyopathy(PPCM ). Methods A total of 21 PPCM and 20 normal delivery femals were randomly recruited in the current study.echocardiographic,hs- CRP,BNP were measured.21PPCM were fol owed up for a month. Results The PPCM patients compared to the controls, BNP(870.1ng/L) and hs- CRP (28.1mg/L) were significantly higher in the PPCM patients compared with the control (99.2ng/L and 6.7mg/L) hs- CRP was positively related with BNP(r=0.67,P<0.01).After a month of treatment,left ventricular ejection fraction enhanced from 33.1%to 50.3%, BNP significantly declined from 870.1ng/L to 196.6ng/L(P<0.01),hs- CRP significantly declined from 28.1mg/L to 7.8mg/L(P<0.01). Conclusion BNP and hs- CRP provide a good reference index for diagnosis and treatment in the PPCM.

  17. Changes of the expression of brain-derived neurotrophic factor and its pro-peptide and synaptophysin in hippocampal neuron after oxygen-glucose deprivation%糖氧剥夺对海马神经元中成熟脑源性神经营养因子及其前体蛋白和突触素的影响

    Institute of Scientific and Technical Information of China (English)

    张露; 崔晓燕; 李俊敏; 张博爱

    2016-01-01

    Objective To investigate the changes of the expression of mature brain-derived neurotrophic factor(mBDNF) and its pro-peptide (pro-BDNF) and synaptophysin (SYP) in vitro culture neuron model damaged by oxygen-glucose deprivation.Methods In vitro primary culture was conducted on the neurons in hippocampus area of newborn SD rats within 24 hours.The damaged neuron model which was ischemic and hypoxic was established by oxygen-glucose deprivation (OGD).The survival of cells suffered by OGD was examined by MTT assay.Protein was extracted from the model 30 min,6 h,12 h and 24 h after OGD,and Western blotting method was used to test mBDNF,pro-BDNF and SYP expression levels in the model at different time points.Results Compared with the control group,the cell activity decreased significantly (P < 0.05),the changes of mBDNF,pro-BDNF and SYP was significant(P < 0.05).With the extension of OGD,mBDNF gradually decreased,wihle pro-BDNF and SYP increased before they were reduced.Conclusions With the injury of hippocampal neuron,OGD can result in the abnormal of cleaving of pro-BDNF and the changes of synaptic transmission and synaptic plasticity.%目的 探讨慢性缺血缺氧对大鼠海马成熟型脑源性神经营养因子(mBDNF)、脑源性神经营养因子前体(pro-BDNF)和突触素(SYP)的影响.方法 提取新生大鼠大脑海马神经元体外培养,随机分为对照组和实验组,培养7d后实验组糖氧剥夺(OGD)处理,实验组分为OGD处理30 min、6h、12 h、24h4个时间点.MTT检测OGD处理后细胞活性.Western blot方法测定不同时间点海马神经元中mBDNF、pro-BDNF和SYP的变化.结果 在OGD处理后的不同时间,与对照组相比细胞活力逐渐下降(P<0.05),mBDNF、pro-BDNF及SYP差异有统计学意义(P<0.05);随缺血缺氧时间的延长,mBDNF蛋白含量逐渐减少,pro-BDNF和SYP蛋白含量均先升高后降低.结论 慢性缺血缺氧导致海马神经元损伤后发生pro-BDNF裂解异常、突触传递及突触可塑性变化.

  18. 慢性心力衰竭患者血浆脑钠肽浓度与体质量指数的相关性%Study on relationship between plamsa brain natriuretic peptide levels and body mass index in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    陈雄; 崔俊友; 李健

    2012-01-01

    目的:探讨慢性心力衰竭患者脑钠肽(BNP)水平与体质量指数(BMI)的关系,明确BNP水平对慢性肥胖心力衰竭患者预后评估的影响.方法:老年充血性心力衰竭患者54例(男性30例,女性24例,左室射血分数<50%),测量患者身高、体重,根据BMI将患者分为3组:对照组(BMI<24 kg·m-2)、超重组(BMI=24~27.9kg·m-2)及肥胖组(BMI≥28kg·m-2),通过免疫荧光方法测定患者血浆BNP水平,比较各组血浆BNP水平及BNP水平与BMI的相关性.结果:(1) 肥胖组患者血浆BNP水平[(1 460±87)ng·L-1]明显低于对照组[(1 857±145)ng·L-1]及超重组[(1 756±100)ng·L-1](均为P<0.01);(2) BNP与BMI之间存在负相关关系(r=-0.91,P<0.01).结论:心力衰竭患者血浆中BNP浓度随BMI增加而降低,在应用BNP对心力衰竭患者进行心功能评价时,应同时考虑肥胖因素对其产生的影响.%Objective; To explore the relationship between levels of plasma brain natriuretic peptide(BNP) and body mass index ( BMI) , and to examine the influence of plasma BNP levels on the prognosis value for obesity heart failure patients. Methods; Fifty-four heart failure patients were enrolled in this study(30 males,24 females and LVEF < 50% ) , and heights and weights of each patient were measured and BMI were calculated with these parameter. The patients were divided into 3 groups according to BMI; controll group ( BMI < 24 kg · m ) , overweight group (BMI =24-27. 9 kg · m~ ) and obese group (BMI <28 kg · m~ ). The plasma concentrations of BNP were measured by immunofluorescence method. Results; The concentrations of BNP were significantly lower in obese group [ ( 1 460 ± 87 ) ng · L ] compared to normal group [ ( 1 857 ± 145 ) ng · L ] and overweight group [ ( 1 756 ± 100)ng · L-1 ] (P <0. 01). BNP levels were inversely correlated with BMI. Conclusion; In heart failure patients, plasma BNP levels are affected by BMI. The influence of BMI must be considered, when assessing the heart

  19. 血浆脑钠肽与同型半胱氨酸的检测在急性冠状动脉综合征诊断中的应用%Application of plasma concentrations of Brain Natriuretic peptide and Homocysteine in the diagnosis of acute cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    胡汉宁; 李小明; 陈薇; 涂建成

    2012-01-01

    目的:探讨血浆脑钠肽(BNP)和同型半胱氨酸(HCY)的浓度变化,在冠状动脉综合征(ACS)患者中的临床意义及其应用价值.方法:选择稳定型心绞痛(SA)31例,不稳定型心绞痛(UA)29例,急性心肌梗死( AMI)45例,健康组65例.入院后第二天清晨或症状发作后24h内采集血标本,分别采用免疫化学发光法测定血中BNP浓度,循环酶法测定血HCY浓度.上述各组中有31例SA、15例UA、25例健康者进行心电图、超声、运动平板实验,在实验前后分别采集血标本,检测运动前后血中BNP,HCY水平的变化.并进行统计学分析.结果:UA组患者血浆BNP浓度分别高于SA组及对照组(P<0.01).AMI组BNP浓度高于UA组(P<0.05).UA组的HCY水平分别高于SA组及对照组(P<0.O1).各组运动平板实验后血中BNP水平显著高于运动前(P<0.01),HCY水平运动前后差异无统计学意义(P>0.05).结论:BNP水平增高表明与心脏缺血或缺氧有关,不稳定心绞痛患者血浆BNP和HCY水平明显升高,AMI组较UA组的更高,提示2者在急性心血管疾病的发病机制中起有重要作用.%Objective;To investigate the clinical significance and application value of the co-relations between plasma concentration variation of Brain natriuretic peptide (BNP) and Homocysteine (HCY) in acute cardiovascular disease. Methods:Stable angina(SA, 31 cases) , unstable angina(UA, 29 cases) , acute myo-cardial infarction(AMI, 45 cases), together with healthy controls(65 cases) were enrolled into this study. Blood samples were taken early next morning or within 24 hours of symptom onset. BNP and HCY levels were determined by Chemiluminescence Immunoassay and Enzymatic cycling assay, respectively. Electrocardiogram, Doppler echocardiography and treadmill exercising test have been applied in 31 SA cases, 15 UA cases and 25 healthy cases. Blood samples were collected before and after the motion for detecting the levels of BNP and HCY. Results: BNP and HCY

  20. 最新糖化血红蛋白水平与急性心力衰竭患者B型尿钠肽、血肌酐的分析%The correlation between brain natriuretic peptide, creatinine and glycosylated hemoglobin in patients with acute heart failure

    Institute of Scientific and Technical Information of China (English)

    赵燕; 韩凌; 杨静娜; 陈欣; 李晓红; 马杰; 陈萍; 孙一光; 胡文泽

    2015-01-01

    Objective To investigate the correlation between brain natriuretic peptide (BNP),creatinine (Cr) and glycosylated hemoglobin in patients with heart failure,and to explore the correlation between glycosylated hemoglobin and heart failure.Methods We selected 106 cases with congestive heart failure in the Fuxing Hospital Affiliated to Capital University of Medical Sciences.We tested BNP,serum creatinine level,evaluation of glycated hemoglobin level of patients with heart failure immediately after admission.Results The BNP levels in patients whose glycosylated hemoglobin level more than 6.5% of BNP levels was (1 356.47 ± 398.69) ng/L,and significantly higher than (686.27 ± 188.31) ng/L of patients whose glycosylated hemoglobin in normal group (P < 0.01).Serum creatinine level(159.32 ±42.31) μ mol/L in patients whose glycosylated hemoglobin level more than 6.5% was significantly higher than creatinine level (105.32 ±11.03) μ mol/L in glycated hemoglobin normal group (P < 0.01).Conclusions Blood BNP,serum ereatinine level in patients with heart failure in the glycosylated hemoglobin level more than 6.5% patients was higher than glycosylated hemoglobin normal level group.The higher glycosylated hemoglobin levels in patients with severe heart failure and poor renal function.The latest glycosylated hemoglobin can be a marker for the risk of heart failure.%目的 通过检测心力衰竭患者B型尿钠肽(BNP)、血肌酐(Cr)与糖化血红蛋白(HbA1c)的水平,探讨HbA1c异常与心力衰竭患者是否存在相关性.方法 入选106例心力衰竭患者,测定患者入院即刻BNP、血Cr水平,评价HbA1c水平异常与心力衰竭患者BNP、血Cr是否存在相关性.结果 HbA1c≥6.5%患者BNP水平(1 356.47±398.69) ng/L明显高于HbA1c正常组的(686.27±188.31) ng/L (P< 0.01).HbA1c≥6.5%患者血Cr水平(159.32±42.31)μ mol/L高于HbA1c正常组的(105.32± 11.03) μmol/L (P<0.01).结论 心力衰竭患者最新HbA1c增高组患者

  1. 脓毒性休克患者血浆脑钠肽与 PiCCO 相关指标的关系%The correlation between plasma brain natriuretic peptide (BNP)levels and parameters of pulse -indicated continuous cardiac output(PiCCO)in patients with septic shock

    Institute of Scientific and Technical Information of China (English)

    吴翔; 陶飞; 胡桂芳; 邓烈华; 姚华国

    2016-01-01

    Objective To investigate the relationship between plasma brain natriuretic peptide (BNP)levels and the monito-ring indicators of pulse -indicated continuous cardiac output (PiCCO)in patients with sepstic shock.Methods 48 patients with septic shock according to the criteria of sepsis set by SC-CN /ESICM/ACCP /ATS /SIS were selected.Clinical and laboratory data including BNP were collected on the 1 d,3rd and 5 th day after admittion.The hemodynamics of the patients was monitored using PiCCO technology,and the heart function indexs were recorded,incluing CI,CFI,GEF and dP /dPmax.Acute Physiology and Chronic Health Evaluation (APACHEⅡ)and Sepsis -related Organ Failure Assessment (SOFA)score were determined.The correlation between BNP levels and the above indexs was analyzed.Results The levels of plasma BNP had negative correlation with CI,CFI,GEF (r =-0.339, -0.250, -0.241 ,P 0.05 ).The levels of plasma BNP had significant positive correlation with APACHEII scores and SOFA scores (r =0.509,0.565 ,P <0.05 ). Conclusion The cardiac function could not be reflected by BNP levels in septic shock patients.Plasma BNP levels can re-flect the severity of septic shock in certain degree,and might be considered as a valuable prognostic factor for patients with septic shock.%目的:通过监测脓毒性休克患者血浆脑钠肽(BNP)水平以及脉搏指示连续心排血量(PiCCO)相关指标的变化,探讨脓毒性休克患者脑钠肽水平与心功能的关系。方法选取48例脓毒性休克患者为研究对象,检测患者入 ICU第1、3、5天血浆 BNP 水平,通过 PiCCO 技术对患者进行血流动力学监测,记录反应心功能指标的 CI、CFI、GEF 和 dP/dP-max,并进行 APACHEⅡ、SOFA 评分,分析 BNP 与上述指标的相关性。结果脓毒性休克患者血浆 BNP 水平与 CI 、CFI、GE 呈负相关(r =-0.339、-0.25、-0.241,P <0.05),与 dP/dPmax 无显著相关性(P >0.05

  2. Clinical Significance of Changes in the Level of Brain Natriuretic Peptide in Patients with Pulmonary Heart Disease%肺源性心脏病病程中脑钠肽水平变化的临床意义分析

    Institute of Scientific and Technical Information of China (English)

    王大江

    2015-01-01

    Objective:To investigate the clinical significance of brain natriuretic peptide (BNP) levels in the course of pulmonary heart disease.Method: 67 patients with chronic pulmonary heart disease in our hospital were selected, according to the progress of the disease course they were divided into episodes stage and remission stage.The BNP level was detected by double anti sandwich immunoassay, PaO2 and PaCO2 levels were determined by blood gas analysis. The different periods levels of BNP, PaCO2 and PaO2 were compared.Result:The episodes stage levels of BNP and PaCO2 were respectively (215.83±83.17)ng/L and (52.13±5.38)mm Hg,they were significantly higher than the remission stage levels,the differences were statistically significant(P<0.05). The episodes stage levels of PaO2 was (51.29±4.70) mm Hg,which was significantly lower than that in remission stage, the difference was statistically significant(P<0.05). Conclusion:In the course of pulmonary heart disease, BNP is involved in the pathophysiological process of pulmonary heart disease, which can be used as a reference index to evaluate the curative effect and prognosis.%目的:探讨脑钠肽(BNP)水平变化在肺源性心脏病病程中的临床意义。方法:选取本院收治的慢性肺心病患者67例,根据病程的进展分为发作期和缓解期。采用双抗夹心免疫酶法测定BNP水平,血气分析测定PaO2和PaCO2水平,比较患者不同时期的血浆BNP、PaCO2及PaO2水平。结果:患者发作期BNP及PaCO2水平分别为(215.83±83.17)ng/L和(52.13±5.38)mm Hg,明显高于缓解期,差异均有统计学意义(P<0.05);患者发作期PaO2水平为(51.29±4.70)mm Hg,明显低于缓解期,差异有统计学意义(P<0.05)。结论:在肺源性心脏病患者的病程进展中,血浆BNP参与肺心病的病理生理过程,可作为评估患者疗效和判定预后的参考指标。

  3. 充血性心力衰竭与肺源性心脏病患者血浆BNP水平的比较%Comparison of plasma levels of brain natriuretic peptide in patients with congestive heart failure or lung-derived heart disease

    Institute of Scientific and Technical Information of China (English)

    韦彩雯; 李宏松; 章敬玉; 姚能才; 窦存芳; 石来新; 卢英民

    2011-01-01

    目的:比较充血性心力衰竭(congestive heart failure,CHF)及肺源性心脏病(pulmonary heart disease,PHD)患者急性呼吸困难发作时及缓解后1周血浆脑钠尿肽(BNP)水平的变化并分析其临床意义.方法:采用全血化学发光法测定CHF及PHD患者急性呼吸困难发作时及缓解后1周血浆BNP水平.结果:CHF患者呼吸困难发作时血浆BNP水平明显高于病情缓解后1周血浆BNP水平[(1997 ±865)ng/L vs.(184±114)ng/L,P<0.05],PHD患者呼吸困难发作时血浆BNP水平明显高于病情缓解后1周血浆BNP水平[(679±202)ng/L vs.(145±48)ng/L,P<0.05],呼吸困难发作时CHF组患者血浆BNP水平明显高于PHD组(P<0.05),呼吸困难缓解后1周两组间无显著差异.结论:BNP水平可作为CHF患者病情严重程度及疗效判断的评价指标.也可作为临床协助鉴别CHF呼吸困难与PHD重度肺功能不全呼吸困难的检测指标之一.%AIM: To compare the changes of plasma brain natriuretic peptide ( BNP) levels in patients with congestive heart failure (CHF) or lung-derived heart disease (pulmonary heart disease, PHD) with dyspnea at onset and 1 week after remission. METHODS: Using the whole blood chemiluminescence method, plasma BNP levels in patients with dyspnea were determined at onset and 1 week after remission. RESULTS: At the onset of dyspnea in patients with CHF, plasma BNP levels were significantly higher than those 1 week after remission [ (1997 ±865) ng/L vs. (184 ± 114) ng/L, P <0.05]. Likewise, at the onset of dyspnea in patients with PHD, plasma BNP levels were also significantly higher than those 1 week after remission [(679 ±202) ng/L vs. (145 ±48) ng/L, P<0.05]. However, at the onset of dyspnea, plasma BNP levels in patients with CHF were significantly higher than those in patients with PHD (P <0.05), but no significant difference was observed between groups at 1 week after remission. CONCLUSION; BNP levels reduce with dyspnea remission. BNP levels can serve

  4. Effects of intracoronary recombinant human brain natriuretic peptide on the cardiac function in patients with acute myocardial infarction after percutaneous coronary intervention%冠状动脉内注射重组人脑利钠肽对急性心肌梗死经皮冠状动脉介入治疗患者心功能的影响

    Institute of Scientific and Technical Information of China (English)

    胡国勋; 蔺鹏翔; 常江; 王凤; 闫旭丽; 李立灏

    2013-01-01

    目的:观察经皮冠状动脉(冠脉)介入治疗(PCI)急性心肌梗死(AMI)时冠脉内注射重组人脑利钠肽(rhBNP)的疗效及安全性.方法:将62例采取直接PCI治疗的前壁AMI患者随机分为冠脉内治疗组(21例)、静脉治疗组(21例)及对照组(20例),冠脉内治疗组在梗死相关血管(IRA)开通后立即给予冠脉内注射常规剂量rhBNP治疗,静脉治疗组于IRA开通后即刻静脉给予常规剂量rhBNP治疗,2组均持续使用rhBNP治疗72 h;对照组单纯给予常规药物治疗.观察所有患者的心肌酶动态变化,并于术后1、4及12周行二维超声心动图检查.结果:冠脉内治疗组和静脉治疗组肌酸激酶、肌酸激酶同工酶峰值均明显低于对照组(均P<0.01).术后4周,冠脉内治疗组每搏输出量、左室射血分数、左室舒张末期内径均优于对照组(均P<0.05);术后12周,冠脉内治疗组每搏输出量、左室射血分数、左室舒张末期内径均优于对照组和静脉治疗组(均P<0.05).结论:IRA开通后立即冠脉内使用rhBNP是安全有效的,冠脉内使用rhBNP对AMI患者PCI术后的心肌保护作用及抑制AMI后左室重构作用均优于静脉使用rhBNP.%Objective:To investigate the security and effect of intracoronary recombinant human brain natriuretic peptide (rhBNP) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).Method:A total of 62 patients with AMI after PCI were randomly divided into intracoronary group (n=21),intravenous group (n=21) and control group (n =20).Intracoronary injection followed by a 72-hour continuous rhBNP infusion was administrated in the intracoronary group and intravenous injection followed by a 72-hour continuous rhBNP infusion was administrated in the intravenous group after primary PCI.In the control group,patients received a routine treatment.The security of intracoronary injection of rhBNP and the dynamic changes of myocardial enzyme in all

  5. Peptide-enhanced oral delivery of therapeutic peptides and proteins

    DEFF Research Database (Denmark)

    Kristensen, Mie; Foged, Camilla; Berthelsen, Jens;

    2013-01-01

    throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed......Systemic therapy upon oral delivery of biologics, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients...

  6. 类风湿关节炎合并急性冠状动脉综合征患者血清脑钠肽水平及心功能特点分析%Cardiac function and brain natriuretic peptide in patients with acute coronary syndrome complicated with rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    潘丽丽; 王天

    2015-01-01

    Objective To investigate the cardiac function and brain natriuretic peptide (BNP) level in patients with acute coronary syndrome (ACS) complicated with rheumatoid arthritis (RA).Methods Sixty-eight ACS patients complicated with RA (observation group) and 65 ACS patients without RA (control group) from January 2012 to June 2013 were enrolled.The age,gender,body mass index (BMI),blood pressure,relative risk factors of cardiovascular disease were recorded and compared between the two groups.The levels of high sensitivity C reactive protein (hs-CRP),erythrocyte sedimentation rate (ESR),serum triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),homocysteine (Hcy) and serum brain natriuretic peptide (BNP) were compared between the two groups.The echocardiography was used to determine the changes of cardiac morphology and function.Results The BMI was significantly higher in observation group than that in control group [(28 ±4) kg/m2 vs (25 ±4) kg/m2].There were no differences regarding the age,gender,blood pressure,relative risk factors of cardiovascular disease,and the levels of TG,TC and LDL-C between the two groups.The HDL level was significantly lower in observation group than that in control group[(1.0 ±0.3) mmol/L vs (1.2 ± 0.2) mmol/L] (P < 0.05).The serum CRP,ESR and Hcy levels in observation group were significantly higher than those in control group[(10 ± 6) mg/L vs (4 ± 3) mg/L,(28 ± 16) mm/1 h vs (9 ±4) mm/1 h,(17 ±6) μmol/L vs (14 ±4) μmol/L] (P<0.05).The level of BNP was significantly higher and the LVEF was significantly lower in observation group than that in control group [(387 ± 226)ng/L vs (258 ± 139) ng/L,(44 ± 13)% vs (61 ± 10)%].Reduction of diastolic function was found in 66 cases (96.7%) of observation group,higher than that in control group [62.3% (40/65)] (P < 0.01).Conclusions ACS patients complicated with RA are more likely to be afflicted

  7. Recent development of peptide self-assembly

    Institute of Scientific and Technical Information of China (English)

    Xiubo Zhao; Fang Pan; Jian R. Lu

    2008-01-01

    Amino acids are the building blocks to build peptides and proteins. Recent development in peptide synthesis has however enabled us to mimic this natural process by preparing various long and short peptides possessing different conformations and biological functions. The self-assembly of short designed peptides into molecular nanostructures is becoming a growing interest in nanobiotechnology. Self-assembled peptides exhibit several attractive features for applications in tissue regeneration, drug delivery, biological surface engineering as well as in food science, cosmetic industry and antibiotics. The aim of this review is to introduce the readers to a number of representative studies on peptide self-assembly.

  8. Characterization of Synthetic Peptides by Mass Spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter;

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS an......Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI...

  9. Quantum Brain?

    CERN Document Server

    Mershin, A; Skoulakis, E M C

    2000-01-01

    In order to create a novel model of memory and brain function, we focus our approach on the sub-molecular (electron), molecular (tubulin) and macromolecular (microtubule) components of the neural cytoskeleton. Due to their size and geometry, these systems may be approached using the principles of quantum physics. We identify quantum-physics derived mechanisms conceivably underlying the integrated yet differentiated aspects of memory encoding/recall as well as the molecular basis of the engram. We treat the tubulin molecule as the fundamental computation unit (qubit) in a quantum-computational network that consists of microtubules (MTs), networks of MTs and ultimately entire neurons and neural networks. We derive experimentally testable predictions of our quantum brain hypothesis and perform experiments on these.

  10. Animating Brains

    Science.gov (United States)

    Borck, Cornelius

    2016-01-01

    A recent paper famously accused the rising field of social neuroscience of using faulty statistics under the catchy title ‘Voodoo Correlations in Social Neuroscience’. This Special Issue invites us to take this claim as the starting point for a cross-cultural analysis: in which meaningful ways can recent research in the burgeoning field of functional imaging be described as, contrasted with, or simply compared to animistic practices? And what light does such a reading shed on the dynamics and effectiveness of a century of brain research into higher mental functions? Reviewing the heated debate from 2009 around recent trends in neuroimaging as a possible candidate for current instances of ‘soul catching’, the paper will then compare these forms of primarily image-based brain research with older regimes, revolving around the deciphering of the brain’s electrical activity. How has the move from a decoding paradigm to a representational regime affected the conceptualisation of self, psyche, mind and soul (if there still is such an entity)? And in what ways does modern technoscience provide new tools for animating brains? PMID:27292322

  11. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    pharmacological tools interfering with NCAM functions. Recent progress in our understanding of the structural basis of NCAM-mediated cell adhesion and signaling has allowed a structure-based design of NCAM mimetic peptides. Using this approach a number of peptides termed P2, P1-B, P-3-DE and P-3-G, whose...... sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling a number of peptides derived from NCAM and targeting NCAM heterophilic ligands such as the fibroblast growth factor receptor...... in vitro and in vivo, making them attractive pharmacological tools suitable for drug development for the treatment of neurodegenerative disorders and impaired memory....

  12. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster (Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10-5 kDa, 5-1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10?5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  13. The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery

    Directory of Open Access Journals (Sweden)

    Ayse Baysal

    2014-09-01

    Full Text Available Background and objectives: In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. Methods: In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48 h after operation. The patients enrolled into the study were divided into two groups depending on: (1 Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2 Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1 duration of mechanical ventilation ≥72 h, (2 intensive care unit stay >7days, and (3 mortality. Results: The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n = 35, n = 16, respectively showed significant differences in repeated measurement time points (p = 0.0001. The preoperative brain natriuretic peptide cut-off value of 125.5 pg mL−1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r = 0.67, p = 0.0001. Conclusions: In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5 pg mL−1 are at risk of developing low cardiac

  14. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    Science.gov (United States)

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected b