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Article ; Online: Amitriptyline inhibits bronchoconstriction and directly promotes dilatation of the airways.

Hempel, Paulina / Klein, Virag / Michely, Anna / Böll, Svenja / Rieg, Annette D / Spillner, Jan / Braunschweig, Till / von Stillfried, Saskia / Wagner, Norbert / Martin, Christian / Tenbrock, Klaus / Verjans, Eva

Respiratory research

2023 Volume 24, Issue 1, Page(s) 262

Abstract: Introduction: The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß: Methods: After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with ... ...

Abstract	Introduction: The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß Methods: After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with mediators of bronchoconstriction (endogenous and exogenous acetylcholine, methacholine, serotonin, endothelin, histamine, thromboxane-receptor agonist U46619 and leukotriene LTD4, airway area was monitored in the absence of or with rising concentrations of amitriptyline. Airway dilatation was also investigated in rat PCLS by prior contraction induced by methacholine. As bronchodilators for maximal relaxation, we used IBMX (PDE inhibitor) and salbutamol (ß Results: Our results show amitriptyline to be a potential inhibitor of bronchoconstriction, induced by exogenous or endogenous (EFS) acetylcholine, serotonin and histamine, in PCLS from various species. The effects of endothelin, thromboxane and leukotrienes could not be blocked. In acute bronchoconstriction, amitriptyline seems to act ASM-independent, because ASM-deficiency (Smdp1 Conclusion: Amitriptyline is a drug of high potential, which inhibits acute bronchoconstriction and induces bronchodilatation in pre-contracted airways. It could be one of the first therapeutic agents in asthmatic disease to have powerful effects on the T
MeSH term(s)	Mice ; Rats ; Humans ; Animals ; Guinea Pigs ; Bronchoconstriction ; Methacholine Chloride/pharmacology ; Amitriptyline/pharmacology ; Amitriptyline/therapeutic use ; Histamine/pharmacology ; Bronchodilator Agents/pharmacology ; Bronchodilator Agents/therapeutic use ; Serotonin/pharmacology ; Serotonin/therapeutic use ; Acetylcholine/pharmacology ; Sympathomimetics/pharmacology ; Sympathomimetics/therapeutic use ; 1-Methyl-3-isobutylxanthine/pharmacology ; 1-Methyl-3-isobutylxanthine/therapeutic use ; Dilatation ; Lung ; Asthma/drug therapy ; Albuterol ; Endothelins/pharmacology ; Endothelins/therapeutic use ; Thromboxanes/pharmacology ; Thromboxanes/therapeutic use
Chemical Substances	Methacholine Chloride (0W5ETF9M2K) ; Amitriptyline (1806D8D52K) ; Histamine (820484N8I3) ; Bronchodilator Agents ; Serotonin (333DO1RDJY) ; Acetylcholine (N9YNS0M02X) ; Sympathomimetics ; 1-Methyl-3-isobutylxanthine (TBT296U68M) ; Albuterol (QF8SVZ843E) ; Endothelins ; Thromboxanes
Language	English
Publishing date	2023-10-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-023-02580-6
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Article ; Online: Platelet-derived growth factor (PDGF)-BB regulates the airway tone via activation of MAP2K, thromboxane, actin polymerisation and Ca

Rieg, Annette D / Suleiman, Said / Anker, Carolin / Bünting, Nina A / Verjans, Eva / Spillner, Jan / Kalverkamp, Sebastian / von Stillfried, Saskia / Braunschweig, Till / Uhlig, Stefan / Martin, Christian

Respiratory research

2022 Volume 23, Issue 1, Page(s) 189

Abstract: Background: PDGFR-inhibition by the tyrosine kinase inhibitor (TKI) nintedanib attenuates the progress of idiopathic pulmonary fibrosis (IPF). However, the effects of PDGF-BB on the airway tone are almost unknown. We studied this issue and the ... ...

Abstract	Background: PDGFR-inhibition by the tyrosine kinase inhibitor (TKI) nintedanib attenuates the progress of idiopathic pulmonary fibrosis (IPF). However, the effects of PDGF-BB on the airway tone are almost unknown. We studied this issue and the mechanisms beyond, using isolated perfused lungs (IPL) of guinea pigs (GPs) and precision-cut lung slices (PCLS) of GPs and humans. Methods: IPL: PDGF-BB was perfused after or without pre-treatment with the TKI imatinib (perfused/nebulised) and its effects on the tidal volume (TV), the dynamic compliance (Cdyn) and the resistance were studied. Pcls (gp): The bronchoconstrictive effects of PDGF-BB and the mechanisms beyond were evaluated. PCLS (human): The bronchoconstrictive effects of PDGF-BB and the bronchorelaxant effects of imatinib were studied. All changes of the airway tone were measured by videomicroscopy and indicated as changes of the initial airway area. Results: PCLS (GP/human): PDGF-BB lead to a contraction of airways. IPL: PDGF-BB decreased TV and Cdyn, whereas the resistance did not increase significantly. In both models, inhibition of PDGFR-(β) (imatinib/SU6668) prevented the bronchoconstrictive effect of PDGF-BB. The mechanisms beyond PDGF-BB-induced bronchoconstriction include activation of MAP2K and TP-receptors, actin polymerisation and Ca Conclusions: PDGFR regulates the airway tone. In PCLS from GPs, this regulatory mechanism depends on the β-subunit. Hence, PDGFR-inhibition may not only represent a target to improve chronic airway disease such as IPF, but may also provide acute bronchodilation in asthma. Since asthma therapy uses topical application. This is even more relevant, as nebulisation of imatinib also appears to be effective.
MeSH term(s)	Actins ; Animals ; Asthma ; Becaplermin ; Guinea Pigs ; Humans ; Imatinib Mesylate/pharmacology ; Mitogen-Activated Protein Kinase Kinases ; Niacinamide ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-sis ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Thromboxanes
Chemical Substances	Actins ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins c-sis ; Thromboxanes ; Becaplermin (1B56C968OA) ; Niacinamide (25X51I8RD4) ; Imatinib Mesylate (8A1O1M485B) ; Receptor, Platelet-Derived Growth Factor beta (EC 2.7.10.1) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2)
Language	English
Publishing date	2022-07-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-022-02101-x
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Article ; Online: Ocular Trauma with Ophthalmic Artery Injury as a Rare Cause of Subarachnoid Hemorrhage: a Case Report and Review of the Literature.

Veldeman, Michael / Ridwan, Hani / Hasan, Dimah / Rieg, Annette / Clusmann, Hans / Schubert, Gerrit Alexander

Journal of neurological surgery. Part A, Central European neurosurgery

2021 Volume 84, Issue 3, Page(s) 281–284

Abstract: Background and importance: Traumatic avulsion of the ophthalmic artery is a rare cause of subarachnoid hemorrhage (SAH). In this case, a relative minor fall with isolated ocular trauma caused bulbar dislocation and rupture of the ophthalmic artery in ... ...

Abstract	Background and importance: Traumatic avulsion of the ophthalmic artery is a rare cause of subarachnoid hemorrhage (SAH). In this case, a relative minor fall with isolated ocular trauma caused bulbar dislocation and rupture of the ophthalmic artery in its intracranial segment resulting in subarachnoid bleeding. Clinical presentation: In a female patient in her 70s, a direct penetrating trauma to the orbit by a door handle resulted in basal SAH with blood dispersion into both Sylvian fissures. Cerebral angiography revealed a blunt-ending stump at the origin of the ophthalmic artery. To provide protection against further bleeding, a flow diverter stent was placed in the internal carotid artery to cover the origin of the ophthalmic artery. After a longer intensive care stay complicated by pneumonia and respiratory insufficiency, the patient made a full recovery. Of all four reported cases (including ours), delayed cerebral ischemia was seen in one patient and hydrocephalus in two patients. These potential complications necessitate close observation and fitting treatment similar to aneurysmal SAH. Conclusion: Due to similar physiologic aspects, this type of bleed mimics many aspects of aneurysmal SAH. In this case, we observed no hydrocephalus or the development of delayed cerebral ischemia. This represents, however, the first reported case treated by placement of a flow diverter stent to prevent rebleeding and pseudoaneurysm formation.
MeSH term(s)	Humans ; Female ; Subarachnoid Hemorrhage/diagnostic imaging ; Subarachnoid Hemorrhage/etiology ; Subarachnoid Hemorrhage/surgery ; Ophthalmic Artery/diagnostic imaging ; Ophthalmic Artery/surgery ; Carotid Artery, Internal ; Brain Ischemia ; Hydrocephalus/complications ; Cerebral Angiography
Language	English
Publishing date	2021-06-07
Publishing country	Germany
Document type	Review ; Case Reports ; Journal Article
ZDB-ID	2651663-9
ISSN	2193-6323 ; 2193-6315
ISSN (online)	2193-6323
ISSN	2193-6315
DOI	10.1055/s-0041-1725956
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Article ; Online: Erratum to: Imatinib relaxes the pulmonary venous bed of guinea pigs.

Maihöfer, Nina A / Suleiman, Said / Dreymüller, Daniela / Manley, Paul W / Rossaint, Rolf / Uhlig, Stefan / Martin, Christian / Rieg, Annette D

Respiratory research

2017 Volume 18, Issue 1, Page(s) 121

Language	English
Publishing date	2017--19
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-9921
ISSN (online)	1465-993X
ISSN	1465-9921
DOI	10.1186/s12931-017-0612-z
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Article ; Online: PDGF-BB regulates the pulmonary vascular tone: impact of prostaglandins, calcium, MAPK- and PI3K/AKT/mTOR signalling and actin polymerisation in pulmonary veins of guinea pigs.

Rieg, Annette D / Suleiman, Said / Anker, Carolin / Verjans, Eva / Rossaint, Rolf / Uhlig, Stefan / Martin, Christian

Respiratory research

2018 Volume 19, Issue 1, Page(s) 120

Abstract: Background: Platelet-derived growth factor (PDGF)-BB and its receptor PDGFR are highly expressed in pulmonary hypertension (PH) and mediate proliferation. Recently, we showed that PDGF-BB contracts pulmonary veins (PVs) and that this contraction is ... ...

Abstract	Background: Platelet-derived growth factor (PDGF)-BB and its receptor PDGFR are highly expressed in pulmonary hypertension (PH) and mediate proliferation. Recently, we showed that PDGF-BB contracts pulmonary veins (PVs) and that this contraction is prevented by inhibition of PDGFR-β (imatinib/SU6668). Here, we studied PDGF-BB-induced contraction and downstream-signalling in isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of guinea pigs (GPs). Methods: In IPLs, PDGF-BB was perfused after or without pre-treatment with imatinib (perfused/nebulised), the effects on the pulmonary arterial pressure (P Results: In IPLs, PDGF-BB increased P Conclusions: PDGF-BB/PDGFR regulates the pulmonary vascular tone by the generation of prostaglandins, the increase of calcium, the activation of MAPK- or PI3K/AKT/mTOR signalling and actin remodelling. More insights in PDGF-BB downstream-signalling may contribute to develop new therapeutics for PH.
MeSH term(s)	Actins/metabolism ; Angiogenesis Inducing Agents/pharmacology ; Animals ; Calcium/metabolism ; Female ; Guinea Pigs ; MAP Kinase Signaling System/physiology ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Phosphatidylinositol 3-Kinases/metabolism ; Polymerization/drug effects ; Prostaglandins/metabolism ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-sis/pharmacology ; Pulmonary Veins/drug effects ; Pulmonary Veins/physiology ; TOR Serine-Threonine Kinases/metabolism ; Vasomotor System/drug effects ; Vasomotor System/metabolism
Chemical Substances	Actins ; Angiogenesis Inducing Agents ; Prostaglandins ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins c-sis ; becaplermin (1B56C968OA) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-06-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-9921
ISSN (online)	1465-993X
ISSN	1465-9921
DOI	10.1186/s12931-018-0829-5
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Article ; Online: Imatinib relaxes the pulmonary venous bed of guinea pigs.

Maihöfer, Nina A / Suleiman, Said / Dreymüller, Daniela / Manley, Paul W / Rossaint, Rolf / Uhlig, Stefan / Martin, Christian / Rieg, Annette D

Respiratory research

2017 Volume 18, Issue 1, Page(s) 32

Abstract: Background: Recently, the IMPRES study revealed that systemic imatinib improves exercise capacity in patients with advanced pulmonary arterial hypertension. Imatinib blocks the tyrosine kinase activity of the platelet-derived growth factor (PDGF)- ... ...

Abstract	Background: Recently, the IMPRES study revealed that systemic imatinib improves exercise capacity in patients with advanced pulmonary arterial hypertension. Imatinib blocks the tyrosine kinase activity of the platelet-derived growth factor (PDGF)-receptor (PDGFR), acts antiproliferative and relaxes pulmonary arteries. However so far, the relaxant effects of imatinib on pulmonary veins (PVs) and on the postcapillary resistance are unknown, although pulmonary hypertension (PH) due to left heart disease (LHD) is most common and primarily affects PVs. Next, it is unknown whether activation of PDGFR alters the pulmonary venous tone. Due to the reported adverse effects of systemic imatinib, we evaluated the effects of nebulized imatinib on the postcapillary resistance. Methods: Precision-cut lung slices (PCLS) were prepared from guinea pigs. PVs were pre-constricted with Endothelin-1 (ET-1) and the imatinib-induced relaxation was studied by videomicroscopy; PDGF-BB-related vascular properties were evaluated as well. The effects of perfused/nebulized imatinib on the postcapillary resistance were studied in cavine isolated perfused lungs (IPL). Intracellular cAMP/cGMP was measured by ELISA in PVs. Results: In PCLS, imatinib (100 μM) relaxed pre-constricted PVs (126%). In PVs, imatinib increased cAMP, but not cGMP and inhibition of adenyl cyclase or protein kinase A reduced the imatinib-induced relaxation. Further, inhibition of K Conclusions: Imatinib-induced relaxation depends on cAMP and on the activation of K
Language	English
Publishing date	2017-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-9921
ISSN (online)	1465-993X
ISSN	1465-9921
DOI	10.1186/s12931-017-0514-0
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Article ; Online: Acid sphingomyelinase regulates T

Böll, Svenja / Ziemann, Sebastian / Ohl, Kim / Klemm, Patricia / Rieg, Annette D / Gulbins, Erich / Becker, Katrin Anne / Kamler, Markus / Wagner, Norbert / Uhlig, Stefan / Martin, Christian / Tenbrock, Klaus / Verjans, Eva

Allergy

2019 Volume 75, Issue 3, Page(s) 603–615

Abstract: Background: Allergic diseases and especially allergic asthma are widespread diseases with high prevalence in childhood, but also in adults. Acid sphingomyelinase (ASM) is a key regulator of the sphingolipid pathway. Previous studies defined the ... ...

Abstract	Background: Allergic diseases and especially allergic asthma are widespread diseases with high prevalence in childhood, but also in adults. Acid sphingomyelinase (ASM) is a key regulator of the sphingolipid pathway. Previous studies defined the association of ASM with the pathogenesis of T Methods: To determine the role of Asm under baseline conditions, wild-type (WT) and Asm Results: At baseline, Asm Conclusion: Asm deficiency could induce higher numbers of T
MeSH term(s)	Animals ; Asthma ; Bronchial Hyperreactivity ; Bronchoalveolar Lavage Fluid ; Cytokines ; Disease Models, Animal ; Lung ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Sphingomyelin Phosphodiesterase/genetics ; Th2 Cells
Chemical Substances	Cytokines ; Ovalbumin (9006-59-1) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12)
Language	English
Publishing date	2019-10-08
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.14039
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Article: Ocular Trauma with Ophthalmic Artery Injury as a Rare Cause of Subarachnoid Hemorrhage: a Case Report and Review of the Literature

Veldeman, Michael / Ridwan, Hani / Hasan, Dimah / Rieg, Annette / Clusmann, Hans / Schubert, Gerrit Alexander

Journal of Neurological Surgery Part A: Central European Neurosurgery

2021 Volume 84, Issue 03, Page(s) 281–284

Abstract: Background and Importance: Traumatic avulsion of the ophthalmic artery is a rare cause of subarachnoid hemorrhage (SAH). In this case, a relative minor fall with isolated ocular trauma caused bulbar dislocation and rupture of the ophthalmic artery in ... ...

Abstract	Background and Importance: Traumatic avulsion of the ophthalmic artery is a rare cause of subarachnoid hemorrhage (SAH). In this case, a relative minor fall with isolated ocular trauma caused bulbar dislocation and rupture of the ophthalmic artery in its intracranial segment resulting in subarachnoid bleeding. Clinical Presentation: In a female patient in her 70s, a direct penetrating trauma to the orbit by a door handle resulted in basal SAH with blood dispersion into both Sylvian fissures. Cerebral angiography revealed a blunt-ending stump at the origin of the ophthalmic artery. To provide protection against further bleeding, a flow diverter stent was placed in the internal carotid artery to cover the origin of the ophthalmic artery. After a longer intensive care stay complicated by pneumonia and respiratory insufficiency, the patient made a full recovery. Of all four reported cases (including ours), delayed cerebral ischemia was seen in one patient and hydrocephalus in two patients. These potential complications necessitate close observation and fitting treatment similar to aneurysmal SAH. Conclusion: Due to similar physiologic aspects, this type of bleed mimics many aspects of aneurysmal SAH. In this case, we observed no hydrocephalus or the development of delayed cerebral ischemia. This represents, however, the first reported case treated by placement of a flow diverter stent to prevent rebleeding and pseudoaneurysm formation.
Keywords	subarachnoid hemorrhage ; ocular trauma ; traumatic brain injury ; flow diverter stent ; ophthalmic artery avulsion
Language	English
Publishing date	2021-06-07
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2651663-9
ISSN	2193-6323 ; 2193-6315
ISSN (online)	2193-6323
ISSN	2193-6315
DOI	10.1055/s-0041-1725956
Database	Thieme publisher's database

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Article ; Online: Short-course versus long-course antibiotic treatment for uncomplicated vancomycin-resistant enterococcal bacteraemia: a retrospective multicentre cohort study.

Bahrs, Christina / Rieg, Siegbert / Hennigs, Annette / Hitzenbichler, Florian / Brehm, Thomas T / Rose, Norman / Jacobi, Rebecca J / Heine, Valerie / Hornuss, Daniel / Huppertz, Gunnar / Hagel, Stefan / Hanses, Frank

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2022 Volume 29, Issue 2, Page(s) 200–207

Abstract: Objectives: The optimal treatment duration for vancomycin-resistant enterococcal (VRE) bacteraemia is still a matter of debate. The aim of the present study was to compare short-course (≤9 days) and long-course (≥10 days) antibiotic treatments in ... ...

Abstract	Objectives: The optimal treatment duration for vancomycin-resistant enterococcal (VRE) bacteraemia is still a matter of debate. The aim of the present study was to compare short-course (≤9 days) and long-course (≥10 days) antibiotic treatments in hospitalized adult patients with uncomplicated VRE bacteraemia. Methods: This retrospective study was conducted in four university hospitals in Germany. Adult patients with a positive blood culture for a VRE were screened from 1 January 2016 to 31 December 2018. Only patients who received a VRE-active antibiotic for at least 48 hours were included. The exclusion criteria were a survival of <10 days and a deep-seated source of infection requiring prolonged treatment. To compare the outcome of short-course therapy with that of long-course therapy, 30-day and 90-day overall mortality, relapse within 90 days, duration of hospitalization, and potential antibiotic-related adverse events were analysed by inverse probability of treatment weighting using the propensity score and by additional covariate adjustment. Results: Of the 363 patients screened, 219 (60.3%) patients were included in the final analysis. Among them, 48 (21.9%) patients had underlying haematological diseases. Seventy-eight (35.6%) patients received short-course treatment (median, 7 days; interquartile range, 5-8 days) and 141 (64.4%) patients received long-course treatment (median, 15 days; interquartile range, 12-23.5 days). Thirty-day mortality was similar in both groups (19.2% vs. 22.0%; adjusted OR, 1.15; p 0.773). Duration of hospitalization (in total and after onset of bacteraemia) was significantly shorter (p < 0.05) in the short-course treatment group, whereas other secondary outcome parameters did not differ between both groups. Discussion: Our study suggests that short-course treatment might not be associated with a worse outcome in patients with uncomplicated VRE bacteraemia.
MeSH term(s)	Adult ; Humans ; Vancomycin/therapeutic use ; Retrospective Studies ; Cohort Studies ; Anti-Bacterial Agents ; Bacteremia/microbiology ; Vancomycin-Resistant Enterococci ; Gram-Positive Bacterial Infections/drug therapy ; Gram-Positive Bacterial Infections/microbiology
Chemical Substances	Vancomycin (6Q205EH1VU) ; Anti-Bacterial Agents
Language	English
Publishing date	2022-09-07
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2022.08.023
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Article ; Online: Tyrosine kinase inhibitors relax pulmonary arteries in human and murine precision-cut lung slices.

Rieg, Annette D / Bünting, Nina A / Cranen, Christian / Suleiman, Said / Spillner, Jan W / Schnöring, Heike / Schröder, Thomas / von Stillfried, Saskia / Braunschweig, Till / Manley, Paul W / Schälte, Gereon / Rossaint, Rolf / Uhlig, Stefan / Martin, Christian

Respiratory research

2019 Volume 20, Issue 1, Page(s) 111

Abstract: Background: Tyrosine kinase inhibitors (TKIs) inhibit the platelet derived growth factor receptor (PDGFR) and gain increasing significance in the therapy of proliferative diseases, e.g. pulmonary arterial hypertension (PAH). Moreover, TKIs relax ... ...

Abstract	Background: Tyrosine kinase inhibitors (TKIs) inhibit the platelet derived growth factor receptor (PDGFR) and gain increasing significance in the therapy of proliferative diseases, e.g. pulmonary arterial hypertension (PAH). Moreover, TKIs relax pulmonary vessels of rats and guinea pigs. So far, it is unknown, whether TKIs exert relaxation in human and murine pulmonary vessels. Thus, we studied the effects of TKIs and the PDGFR-agonist PDGF-BB in precision-cut lung slices (PCLS) from both species. Methods: The vascular effects of imatinib (mice/human) or nilotinib (human) were studied in Endothelin-1 (ET-1) pre-constricted pulmonary arteries (PAs) or veins (PVs) by videomicroscopy. Baseline initial vessel area (IVA) was defined as 100%. With regard to TKI-induced relaxation, K Results: Murine PCLS: Imatinib (10 μM) relaxed ET-1-pre-constricted PAs to 167% of IVA. Vice versa, 100 nM PDGF-BB contracted PAs to 60% of IVA and pre-treatment with imatinib or amlodipine prevented PDGF-BB-induced contraction. Murine PVs reacted only slightly to imatinib or PDGF-BB. Human PCLS: 100 μM imatinib or nilotinib relaxed ET-1-pre-constricted PAs to 166% or 145% of IVA, respectively, due to the activation of K Conclusions: TKIs relax pre-constricted PAs/PVs from both, mice and humans. In human PAs, the activation of K
MeSH term(s)	Animals ; Dose-Response Relationship, Drug ; Female ; Humans ; Lung/blood supply ; Lung/drug effects ; Lung/physiology ; Mice ; Mice, Inbred BALB C ; Protein Kinase Inhibitors/pharmacology ; Pulmonary Artery/drug effects ; Pulmonary Artery/physiology ; Species Specificity ; Vasodilation/drug effects ; Vasodilation/physiology
Chemical Substances	Protein Kinase Inhibitors
Language	English
Publishing date	2019-06-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-9921
ISSN (online)	1465-993X
ISSN	1465-9921
DOI	10.1186/s12931-019-1074-2
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