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Article: Effects of neuropeptide Y2 receptor blockade on ventricular arrhythmias in rats with acute myocardial infarction.

Omerovic, Elmir / Råmunddal, Truls / Lorentzon, Malin / Nordlander, Margareta

2007 Volume 565, Issue 1-3, Page(s) 138–143

Abstract: Excessive sympathetic activity is believed to be the key arrhythmogenic factor both in the setting of acute myocardial infarction and during chronic heart failure. The aim of this study was to evaluate the effect of neuropeptide Y2 blockade on malignant ... ...

Abstract	Excessive sympathetic activity is believed to be the key arrhythmogenic factor both in the setting of acute myocardial infarction and during chronic heart failure. The aim of this study was to evaluate the effect of neuropeptide Y2 blockade on malignant ventricular arrhythmias in rats with acute myocardial infarction. Vagotonic dose-finding study for neuropeptide Y2 receptor antagonist, (S)-N2-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamid (AR-H05359) was conducted in guinea pigs (n=50) and rats (n=3). Induction of postinfarction arrhythmias was conducted in Sprague-Dawley rats that were randomized into 3 groups. Neuropeptide Y2 antagonist treated rats (n=7), placebo group (n=10) and amiodarone treated rats (n=8). Myocardial infarction was induced by ligation of the left coronary artery. Computerized telemetric ECG tracings were obtained continuously before induction of myocardial infarction and up to 120 min postinfarction. Occurrence of ventricular arrhythmias was analyzed according to a 10-point arrhythmia score. There was no difference in the arrhythmia scores between the neuropeptide Y2 and the saline group. The amiodarone treated animals had lower score compared to the neuropeptide Y2 and the placebo group (p<0.05). The blockade of receptors does not reduce ventricular arrhythmias in the rats with acute myocardial infarction. Further studies are needed to evaluate whether increasing vagal tonus during sympathetic activation may be valuable anti-arrhythmic strategy to prevent sudden death in patients with myocardial infarction and heart failure.
MeSH term(s)	Animals ; Arrhythmias, Cardiac/etiology ; Arrhythmias, Cardiac/prevention & control ; Guinea Pigs ; Male ; Myocardial Infarction/complications ; Rats ; Rats, Sprague-Dawley ; Receptors, Neuropeptide Y/antagonists & inhibitors ; Receptors, Neuropeptide Y/physiology
Chemical Substances	Receptors, Neuropeptide Y ; neuropeptide Y2 receptor
Language	English
Publishing date	2007-06-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2007.03.002
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Zs.A 522: Show issues

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Article: Influence of endogenous neuropeptide Y (NPY) on the sympathetic-parasympathetic interaction in the canine heart.

Ilebekk, Arnfinn / Björkman, Jan-Arne / Nordlander, Margareta

Journal of cardiovascular pharmacology

2005 Volume 46, Issue 4, Page(s) 474–480

Abstract: The purpose of this study was to examine the sympathetic-parasympathetic interactions on heart rate through release of neuropeptide Y (NPY) and its action on prejunctional NPY Y2 receptors on vagal and sympathetic nerve fibers. In other studies on ... ...

Abstract	The purpose of this study was to examine the sympathetic-parasympathetic interactions on heart rate through release of neuropeptide Y (NPY) and its action on prejunctional NPY Y2 receptors on vagal and sympathetic nerve fibers. In other studies on various preparations and in various organs, attenuation of transmitter release has in fact been demonstrated through activation of the NPY Y2 receptor. In the present study on anesthetized dogs we examine, however, for the first time if vagal bradycardia is attenuated by endogenous NPY released during intense cardiac sympathetic stimulation. In addition, we explore if sympathetic transmitter release and heart rate, during moderate sympathetic stimulation, are affected through this receptor system. The significance of the NPY Y2 receptor was revealed by performing experiments before and after administration of its specific receptor antagonist BIIE0246. We found that attenuation of the bradycardia during vagal nerve stimulation was dose-dependently counteracted by BIIE0246 and that the tachycardia elicited by sympathetic stimulation remained unaffected after NPY Y2 receptor blockade. Thus, endogenous NPY appears to attenuate vagal bradycardia by stimulating prejunctional NPY Y2 receptors on cardiac vagal nerve terminals and, less efficiently, to attenuate transmitter release and tachycardia through a feedback loop on the cardiac sympathetic nerve fibers.
MeSH term(s)	Animals ; Arginine/analogs & derivatives ; Arginine/pharmacology ; Benzazepines/pharmacology ; Blood Pressure/physiology ; Catecholamines/metabolism ; Dogs ; Electric Stimulation ; Heart/innervation ; Heart/physiology ; Heart Rate/physiology ; Myocardium/metabolism ; Nerve Fibers/physiology ; Neuropeptide Y/metabolism ; Parasympathetic Nervous System/physiology ; Receptors, Neuropeptide Y/antagonists & inhibitors ; Receptors, Neuropeptide Y/metabolism ; Sympathetic Nervous System/physiology ; Time Factors ; Vagus Nerve/physiology
Chemical Substances	Benzazepines ; Catecholamines ; Neuropeptide Y ; Receptors, Neuropeptide Y ; neuropeptide Y2 receptor ; Arginine (94ZLA3W45F) ; BIIE 0246 (N3Z657H81X)
Language	English
Publishing date	2005-09-08
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/01.fjc.0000177986.21929.d8
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Zs.A 1471: Show issues

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Article: A method for heart rate-corrected estimation of baroreflex sensitivity.

Abrahamsson, Christina / Ahlund, Catherine / Nordlander, Margareta / Lind, Lars

Journal of hypertension

2003 Volume 21, Issue 11, Page(s) 2133–2140

Abstract: Objective: The relationship between the prevailing heart rate (HR) and the baroreflex sensitivity (BRS) is described in the present study together with a method for individual HR-corrected estimations of BRS.: Design: HR and BRS, determined with the ... ...

Abstract	Objective: The relationship between the prevailing heart rate (HR) and the baroreflex sensitivity (BRS) is described in the present study together with a method for individual HR-corrected estimations of BRS. Design: HR and BRS, determined with the sequence method, were measured in ten young healthy subjects during rest, stress, standing and bicycle exercise, i.e. at a wide range of HRs. Results: BRS decreased exponentially with increasing HR. The relationship between the natural logarithm of BRS and HR was linear in each individual and could be described by the equation of a straight line. The equation describing the individual BRS-HR relationship could be derived either from BRS and HR measured during steady-state conditions or from the slope and average HR of the individual sequences occurring throughout the experimental protocol. The latter method was preferable since it did not require recordings during steady-state conditions. In order to eliminate the influence of differences in HR on BRS when comparing BRS between subjects, the equation describing the individual BRS-HR relationship was used to calculate BRS at a HR of 60 bpm, BRS(60), which ranged from 9.5 to 30.1 ms/mmHg for the 10 subjects. Conclusions: Considering the dramatic effect of a small difference in HR on BRS, especially at lower HRs, BRS should be estimated at a wide range of HRs in order to determine the HR-corrected BRS from the individual HR-BRS relationship. Otherwise, comparisons of BRS between different individuals, study groups or following drug treatment or other interventions would be highly dependent on differences in HR and thereby easily misinterpreted.
MeSH term(s)	Adult ; Baroreflex ; Cardiology/methods ; Exercise Test ; Female ; Heart Rate ; Homeostasis ; Humans ; Male ; Posture/physiology ; Regression Analysis ; Rest ; Stress, Physiological/physiopathology
Language	English
Publishing date	2003-09-29
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	605532-1
ISSN	1473-5598 ; 0263-6352 ; 0952-1178
ISSN (online)	1473-5598
ISSN	0263-6352 ; 0952-1178
DOI	10.1097/00004872-200311000-00023
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Zs.A 1885: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 614: Show issues

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Article: Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control.

Nordlander, Margareta / Sjöquist, Per-Ove / Ericsson, Hans / Rydén, Lars

Cardiovascular drug reviews

2004 Volume 22, Issue 3, Page(s) 227–250

Abstract: Clevidipine is an ultrashort-acting vasoselective calcium antagonist under development for short-term intravenous control of blood pressure. Studies in animals, healthy volunteers and patients have demonstrated the vascular selectivity and rapid onset ... ...

Abstract	Clevidipine is an ultrashort-acting vasoselective calcium antagonist under development for short-term intravenous control of blood pressure. Studies in animals, healthy volunteers and patients have demonstrated the vascular selectivity and rapid onset and offset of antihypertensive action of clevidipine, a synthetic 1,4-dihydropyridine that inhibits L-type calcium channels. Clevidipine has a high clearance (0.05 L/min/kg) and is rapidly hydrolyzed to inactive metabolites by esterases in arterial blood. Its half-life in patients undergoing cardiac surgery is less than one min. Unlike sodium nitroprusside, a drug commonly used for the short-term control of blood pressure, which dilates both arterioles and veins, clevidipine reduces blood pressure through a selective effect on arterioles. As documented in animals and in cardiac surgical patients, clevidipine reduces peripheral resistance without any undesirable effect on cardiac filling pressure. It increases stroke volume and cardiac output. In anesthetized patients undergoing cardiac surgery clevidipine, unlike sodium nitroprusside, does not increase heart rate. In addition of having a favorable hemodynamic profile, suitable for rapid control of blood pressure, clevidipine protects against ischemia/reperfusion injuries, which are not uncommon during major surgery. In anesthetized pigs, clevidipine reduced infarct size after 45 min-long myocardial ischemia by 40%. In rats, renal function and splanchnic blood flow were better maintained when blood pressure was reduced with clevidipine than with sodium nitroprusside. Clevidipine was well tolerated in Phases I and II of clinical trials that included more than 300 individuals/patients. Since there are no known compounds with similar pharmacodynamic and pharmacokinetic properties in clinical development, it is anticipated that clevidipine, a compound tailored to the needs of anesthesiologists, has the potential to become a drug of choice for controlling blood pressure during surgical procedures.
MeSH term(s)	Animals ; Blood Pressure/drug effects ; Calcium Channel Blockers/pharmacokinetics ; Calcium Channel Blockers/pharmacology ; Calcium Channel Blockers/therapeutic use ; Cardiotonic Agents/pharmacokinetics ; Cardiotonic Agents/pharmacology ; Cardiotonic Agents/therapeutic use ; Clinical Trials as Topic ; Hemodynamics/drug effects ; Humans ; Hypertension/drug therapy ; Hypertension/physiopathology ; Pyridines/pharmacokinetics ; Pyridines/pharmacology ; Pyridines/therapeutic use ; Reperfusion Injury/drug therapy ; Reperfusion Injury/physiopathology ; Time Factors
Chemical Substances	Calcium Channel Blockers ; Cardiotonic Agents ; Pyridines ; clevidipine (19O2GP3B7Q)
Language	English
Publishing date	2004-09-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645099-4
ISSN	0897-5957
ISSN	0897-5957
DOI	10.1111/j.1527-3466.2004.tb00143.x
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Zs.A 2474: Show issues

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Article: Distribution of neuropeptide Y Y1 and Y2 receptors in the postmortem human heart.

Jönsson-Rylander, Ann Cathrine / Nordlander, Margareta / Svindland, Aud / Ilebekk, Arnfinn

Peptides

2003 Volume 24, Issue 2, Page(s) 255–262

Abstract: In the present study, we present for the first time the presence and distribution of neuropeptide Y (NPY) receptors Y1 and Y2 in the human postmortem heart using specific antibodies raised against extracellular parts of the receptors. A more intensive ... ...

Abstract	In the present study, we present for the first time the presence and distribution of neuropeptide Y (NPY) receptors Y1 and Y2 in the human postmortem heart using specific antibodies raised against extracellular parts of the receptors. A more intensive staining against the Y2 than against the Y1 receptors was detected on both atrial and ventricular cardiomyocytes. Immunoreactivity against both receptors was identified on both conducting fibers and cardiac nerves. More vessels stained positively for the Y2 than for the Y1 receptor, but the Y1 receptors were more abundant in subendocardial than subepicardial vessels of the left ventricular wall.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Autopsy ; Blood Vessels/chemistry ; Blood Vessels/pathology ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Myocardium/chemistry ; Myocardium/pathology ; Receptors, Neuropeptide Y/analysis
Chemical Substances	Receptors, Neuropeptide Y ; neuropeptide Y-Y1 receptor ; neuropeptide Y2 receptor
Language	English
Publishing date	2003-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/s0196-9781(03)00041-x
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Zs.A 1649: Show issues

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Article: Ventricular fibrillation induced by ischemia-reperfusion is not prevented by the NPY Y2 receptor antagonist BIIE0246.

Ilebekk, Arnfinn / Eriksen, Morten / Sevre, Knut / Aspelin, Trude / Björkman, Jan-Arne / Lyberg, Torstein / Nordlander, Margareta

Journal of cardiovascular pharmacology and therapeutics

2006 Volume 11, Issue 3, Page(s) 177–183

Abstract: Neuropeptide Y is released together with norepinephrine from sympathetic nerve terminals during conditions of increased sympathetic activity. Neuropeptide Y is known to inhibit vagal activity, and accordingly, it might increase the risk for ventricular ... ...

Abstract	Neuropeptide Y is released together with norepinephrine from sympathetic nerve terminals during conditions of increased sympathetic activity. Neuropeptide Y is known to inhibit vagal activity, and accordingly, it might increase the risk for ventricular fibrillation during myocardial ischemia-reperfusion, with concomitant sympathetic stimulation. Counteracting the inhibiting effect of neuropeptide Y by the specific neuropeptide Y2 antagonist, BIIE0246, we expected occurrence of ventricular fibrillation in association with repeated periods of myocardial ischemia-reperfusion to decrease. The midleft anterior descending coronary artery was repeatedly occluded in 16 open-chest pigs. Eight pigs received BIIE0246, and the controls received the vehicle only. Ventricular fibrillation developed in 2 animals of the control group, but in 4 pigs receiving BIIE0246. Occurrence of ventricular fibrillation and ventricular tachycardia did not differ significantly between the 2 groups, and in association with repeated periods of regional myocardial ischemia, did not decline in pigs treated by the specific neuropeptide Y2-receptor antagonist BIIE0246.
MeSH term(s)	Animals ; Arginine/analogs & derivatives ; Arginine/blood ; Arginine/pharmacology ; Benzazepines/blood ; Benzazepines/pharmacology ; Biomarkers/blood ; Blood Pressure/drug effects ; Body Temperature/drug effects ; Carbon Dioxide/analysis ; Carbon Dioxide/blood ; Cardiac Output/drug effects ; Coronary Circulation/drug effects ; Coronary Stenosis/complications ; Disease Models, Animal ; Female ; Heart Rate/drug effects ; Hematocrit ; Male ; Myocardial Reperfusion/adverse effects ; Myocardial Reperfusion Injury/etiology ; Myocardial Reperfusion Injury/prevention & control ; Oxygen/analysis ; Oxygen/blood ; Potassium/blood ; Receptors, Neuropeptide Y/antagonists & inhibitors ; Receptors, Neuropeptide Y/blood ; Swine ; Tachycardia, Ventricular/etiology ; Tachycardia, Ventricular/physiopathology ; Tachycardia, Ventricular/prevention & control ; Ventricular Fibrillation/etiology ; Ventricular Fibrillation/physiopathology ; Ventricular Fibrillation/prevention & control
Chemical Substances	Benzazepines ; Biomarkers ; Receptors, Neuropeptide Y ; neuropeptide Y2 receptor ; Carbon Dioxide (142M471B3J) ; Arginine (94ZLA3W45F) ; BIIE 0246 (N3Z657H81X) ; Potassium (RWP5GA015D) ; Oxygen (S88TT14065)
Language	English
Publishing date	2006-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1329372-2
ISSN	1074-2484
ISSN	1074-2484
DOI	10.1177/1074248406292709
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Zs.A 4895: Show issues

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Article: Evaluation of ST-segment changes during and after maximal exercise tests in one-, two- and three-vessel coronary artery disease.

Bjurö, Thorvald / Gullestad, Lars / Endresen, Knut / Nordlander, Margareta / Malm, Anders / Höglund, Lena / Wahlqvist, Inger / Pernow, John

Scandinavian cardiovascular journal : SCJ

2004 Volume 38, Issue 5, Page(s) 270–277

Abstract: Objective: To relate ECG and heart rate (HR) variables during and after exercise testing with the presence of one-, two- or three-vessel disease defined by angiography.: Design: Seventy-three male patients with stable angina pectoris and ... ...

Abstract	Objective: To relate ECG and heart rate (HR) variables during and after exercise testing with the presence of one-, two- or three-vessel disease defined by angiography. Design: Seventy-three male patients with stable angina pectoris and angiographically verified coronary artery disease underwent a maximal exercise test. From 12-lead ECG recordings and computer averaging ST-amplitude and HR data were measured in consecutive 10-s intervals. Results: In univariate analysis, patients with three-vessel disease had lower maximal exercise capacity, a shorter time to >1 mm ST-depression, more often a clockwise ST/HR recovery loop, more frequently a post-exercise downward ST-segment slope, and a greater ST-deficit at 3.5 min after exercise than patients with one-vessel disease. In multivariate analysis, time to >1 mm ST-depression discriminated between patients with three- and one-vessel disease. In patients with an intermediate time to >1 mm ST-depression a clockwise ST/HR recovery loop and/or a downsloping ST-segment in the post-exercise period were significantly more prevalent in severe vessel disease. Conclusion: Patients with three-vessel disease had a significantly shorter time to >1 mm ST-depression during exercise and more often an abnormal post-exercise ST/HR reaction than those with one-vessel disease.
MeSH term(s)	Adult ; Aged ; Angina Pectoris/diagnosis ; Coronary Angiography ; Coronary Artery Disease/classification ; Coronary Artery Disease/diagnosis ; Coronary Artery Disease/diagnostic imaging ; Coronary Artery Disease/physiopathology ; Electrocardiography ; Exercise Test ; Humans ; Male ; Middle Aged ; Reference Values ; Stroke Volume ; Time Factors
Language	English
Publishing date	2004-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1379906-x
ISSN	1651-2006 ; 1401-7431
ISSN (online)	1651-2006
ISSN	1401-7431
DOI	10.1080/14017430410021606
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Zs.A 638: Show issues

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Article: Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing.

Ekstrand, A Jonas / Cao, Renhai / Bjorndahl, Meit / Nystrom, Susanne / Jonsson-Rylander, Ann-Cathrine / Hassani, Hessameh / Hallberg, Bengt / Nordlander, Margareta / Cao, Yihai

Proceedings of the National Academy of Sciences of the United States of America

2003 Volume 100, Issue 10, Page(s) 6033–6038

Abstract: Neuropeptide Y (NPY), a 36-aa peptide, is widely distributed in the brain and peripheral tissues. Whereas physiological roles of NPY as a hormoneneurotransmitter have been well studied, little is known about its other peripheral functions. Here, we ... ...

Abstract	Neuropeptide Y (NPY), a 36-aa peptide, is widely distributed in the brain and peripheral tissues. Whereas physiological roles of NPY as a hormoneneurotransmitter have been well studied, little is known about its other peripheral functions. Here, we report that NPY acts as a potent angiogenic factor in vivo using the mouse corneal micropocket and the chick chorioallantoic membrane (CAM) assays. Unlike vascular endothelial growth factor (VEGF), microvessels induced by NPY had distinct vascular tree-like structures showing vasodilation. This angiogenic pattern was similar to that induced by fibroblast growth factor-2, and the angiogenic response was dose-dependent. In the developing chick embryo, NPY stimulated vascular sprouting from preexisting blood vessels. When [Leu(31)Pro(34)]NPY, a NPY-based analogue lacking high affinity for the NPY Y(2) receptor but capable of stimulating both Y(1) and Y(5) receptors, was used in the corneal model, no angiogenic response could be detected. In addition, NPY failed to induce angiogenesis in Y(2) receptor-null mice, suggesting that this NPY receptor subtype was mediating the angiogenic signal. In support of this finding, the Y(2) receptor, but not Y(1), Y(4), or Y(5) receptors, was found to be widely expressed in newly formed blood vessels. Further, a delay of skin wound healing with reduced neovascularization was found in Y(2) receptor-null mice. These data demonstrate that NPY may play an important role in the regulation of angiogenesis and angiogenesis-dependent tissue repair.
MeSH term(s)	Amino Acid Sequence ; Animals ; Blood Vessels/physiology ; Chick Embryo ; Cornea/physiology ; Corneal Transplantation/physiology ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Neovascularization, Physiologic/drug effects ; Neuropeptide Y/pharmacology ; Peptide Fragments/chemistry ; Receptors, Neuropeptide Y/deficiency ; Receptors, Neuropeptide Y/genetics ; Wound Healing/genetics
Chemical Substances	Neuropeptide Y ; Peptide Fragments ; Receptors, Neuropeptide Y ; neuropeptide Y2 receptor
Language	English
Publishing date	2003-05-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1135965100
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Zs.A 1148: Show issues

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Article ; Online: Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial.

Bergman, Peter / Blennow, Ola / Hansson, Lotta / Mielke, Stephan / Nowak, Piotr / Chen, Puran / Söderdahl, Gunnar / Österborg, Anders / Smith, C I Edvard / Wullimann, David / Vesterbacka, Jan / Lindgren, Gustaf / Blixt, Lisa / Friman, Gustav / Wahren-Borgström, Emilie / Nordlander, Anna / Gomez, Angelica Cuapio / Akber, Mira / Valentini, Davide /

Norlin, Anna-Carin / Thalme, Anders / Bogdanovic, Gordana / Muschiol, Sandra / Nilsson, Peter / Hober, Sophia / Loré, Karin / Chen, Margaret Sällberg / Buggert, Marcus / Ljunggren, Hans-Gustaf / Ljungman, Per / Aleman, Soo

EBioMedicine

2021 Volume 74, Page(s) 103705

Abstract: Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in ...

Abstract	Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. Funding: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.
MeSH term(s)	Adenine/adverse effects ; Adenine/analogs & derivatives ; Adenine/therapeutic use ; Antibodies, Viral/blood ; BNT162 Vaccine/adverse effects ; BNT162 Vaccine/immunology ; COVID-19/prevention & control ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunocompromised Host/immunology ; Immunogenicity, Vaccine/immunology ; Immunotherapy, Adoptive ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects ; Mycophenolic Acid/therapeutic use ; Organ Transplantation ; Piperidines/adverse effects ; Piperidines/therapeutic use ; Primary Immunodeficiency Diseases/immunology ; Prospective Studies ; SARS-CoV-2/immunology ; Seroconversion ; Spike Glycoprotein, Coronavirus/immunology ; Vaccination/adverse effects ; Vaccine Efficacy
Chemical Substances	Antibodies, Viral ; Piperidines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ibrutinib (1X70OSD4VX) ; Mycophenolic Acid (HU9DX48N0T) ; Adenine (JAC85A2161) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-11-30
Publishing country	Netherlands
Document type	Clinical Trial ; Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2021.103705
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Zs.A 7090: Show issues

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Article: Clevidipine in adult cardiac surgical patients: a dose-finding study.

Bailey, James M / Lu, Wei / Levy, Jerrold H / Ramsay, James G / Shore-Lesserson, Linda / Prielipp, Richard C / Brister, Neil W / Roach, Gary W / Jolin-Mellgard, Ase / Nordlander, Margareta

Anesthesiology

2002 Volume 96, Issue 5, Page(s) 1086–1094

Abstract: Background: Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the ... ...

Abstract	Background: Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients. Methods: Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration-response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis. Results: There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 microg. kg-1. min-1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 microg/l and for a 20% or greater decrease in mean arterial pressure was 26.3 microg/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration. Conclusion: Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.
MeSH term(s)	Algorithms ; Antihypertensive Agents/administration & dosage ; Antihypertensive Agents/pharmacokinetics ; Antihypertensive Agents/therapeutic use ; Blood Pressure/drug effects ; Calcium Channel Blockers/administration & dosage ; Calcium Channel Blockers/pharmacokinetics ; Calcium Channel Blockers/therapeutic use ; Cardiac Surgical Procedures ; Dose-Response Relationship, Drug ; Female ; Half-Life ; Heart Rate/drug effects ; Hemodynamics/drug effects ; Humans ; Male ; Middle Aged ; Pyridines/administration & dosage ; Pyridines/pharmacokinetics ; Pyridines/therapeutic use ; Vascular Resistance/drug effects
Chemical Substances	Antihypertensive Agents ; Calcium Channel Blockers ; Pyridines ; clevidipine (19O2GP3B7Q)
Language	English
Publishing date	2002-04-23
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	269-0
ISSN	0003-3022
ISSN	0003-3022
DOI	10.1097/00000542-200205000-00010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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