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Article ; Online: Acute daily exposure to ambient air pollution impairs endothelium-dependent vasodilator responses in young, healthy individuals.

Jasiewicz-Honkisz, B / Osmenda, G / Wilk, G / Urbanski, K / Luc, K / Guzik, B / Mikołajczyk, T P / Guzik, T J

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society

2023 Volume 74, Issue 4

Abstract: Exposure to ambient air pollution influences cardiovascular (CV) morbidity and mortality. The differential effects of changing particulate or gaseous air pollution on endothelial function in young healthy individuals remain unclear. The aim of this study ...

Abstract	Exposure to ambient air pollution influences cardiovascular (CV) morbidity and mortality. The differential effects of changing particulate or gaseous air pollution on endothelial function in young healthy individuals remain unclear. The aim of this study was to evaluate the relationships between exposures to different pollutants and vascular function in a group of 39 young (33±11 years old) subjects with low CV risk. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were performed, when air pollution reached highest levels (heating period) and repeated in a subgroup of 18 participants a few months later (just before the heating period starts). Daily mean concentrations of PM2.5 and PM10 were inversely correlated with FMD, and this relationship remained significant after adjusting for factors known to affect vascular dysfunction. Endothelial function did not differ between the two time points studied. However, we observed a strong inverse association between the change in the concentration of particulate matter (deltaPM2.5 and deltaPM10) and the change in FMD (deltaFMD) between the two visits (R= -0.65, p= 0.02; R= -0.64, p= 0.02, respectively). In summary, we provide evidence that the concentration of PM2.5 and PM10, but not SO
MeSH term(s)	Humans ; Young Adult ; Adult ; Air Pollutants/adverse effects ; Air Pollutants/analysis ; Endothelium-Dependent Relaxing Factors ; Vasodilator Agents ; Air Pollution/adverse effects ; Air Pollution/analysis ; Particulate Matter/adverse effects ; Particulate Matter/analysis
Chemical Substances	Air Pollutants ; Endothelium-Dependent Relaxing Factors ; Vasodilator Agents ; Particulate Matter
Language	English
Publishing date	2023-10-16
Publishing country	Poland
Document type	Journal Article
ZDB-ID	1125221-2
ISSN	1899-1505 ; 0867-5910 ; 0044-6033
ISSN (online)	1899-1505
ISSN	0867-5910 ; 0044-6033
DOI	10.26402/jpp.2023.4.03
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Article ; Online: Oxidative stress and inflammatory markers in prediabetes and diabetes.

Luc, K / Schramm-Luc, A / Guzik, T J / Mikolajczyk, T P

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society

2020 Volume 70, Issue 6

Abstract: Prediabetes is a state of elevated plasma glucose in which the threshold for diabetes has not yet been reached and can predispose to the development of type 2 diabetes and cardiovascular diseases. Insulin resistance and impaired beta-cell function are ... ...

Abstract	Prediabetes is a state of elevated plasma glucose in which the threshold for diabetes has not yet been reached and can predispose to the development of type 2 diabetes and cardiovascular diseases. Insulin resistance and impaired beta-cell function are often already present in prediabetes. Hyperglycemia can upregulate markers of chronic inflammation and contribute to increased reactive oxygen species (ROS) generation, which ultimately cause vascular dysfunction. Conversely, increased oxidative stress and inflammation can lead to insulin resistance and impaired insulin secretion. Proper treatment of hyperglycemia and inhibition of ROS overproduction is crucial for delaying onset of diabetes and for prevention of cardiovascular complications. Thus, it is imperative to determine the mechanisms involved in the progression from prediabetes to diabetes including a clarification of how old and new medications affect oxidative and immune mechanisms of diabetes. In this review, we discuss the relationship between oxidative stress and hyperglycemia along with links between inflammation and prediabetes. Additionally, the effects of hyperglycemic memory, microvesicles, micro-RNA, and epigenetic regulation on inflammation, oxidative state, and glycemic control are highlighted. Adipose tissue and their influence on chronic inflammation are also briefly reviewed. Finally, the role of immune-targeted therapies and anti-diabetic medication on glycemic control and oxidative stress are discussed.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Blood Glucose/metabolism ; Cardiovascular Diseases/etiology ; Diabetes Mellitus, Type 2/physiopathology ; Epigenesis, Genetic ; Humans ; Hyperglycemia/physiopathology ; Inflammation/physiopathology ; Insulin Resistance ; Oxidative Stress/physiology ; Prediabetic State/physiopathology ; Reactive Oxygen Species/metabolism
Chemical Substances	Biomarkers ; Blood Glucose ; Reactive Oxygen Species
Language	English
Publishing date	2020-02-19
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	1125221-2
ISSN	1899-1505 ; 0867-5910 ; 0044-6033
ISSN (online)	1899-1505
ISSN	0867-5910 ; 0044-6033
DOI	10.26402/jpp.2019.6.01
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Article ; Online: Systemic and vascular inflammation in experimental allergic asthma.

Konior-Rozlachowska, A / Siedlinski, M / Szczepaniak, P / Nosalski, R / Murray, E / Mikolajczyk, T P

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society

2021 Volume 72, Issue 2

Abstract: Allergic asthma and atherosclerosis are inflammatory diseases characterized by similar sets of circulating inflammatory cells, in addition to mast cells in the airway and vessel wall. Animal models and human studies provide evidence of a potential ... ...

Abstract	Allergic asthma and atherosclerosis are inflammatory diseases characterized by similar sets of circulating inflammatory cells, in addition to mast cells in the airway and vessel wall. Animal models and human studies provide evidence of a potential interaction between the two apparently unrelated diseases. The main objective of this study was to determine whether experimental allergic asthma is accompanied by inflammatory responses, measured as the activation of the vasculature and the presence of immune cells in the perivascular adipose tissue. For this purpose, male Dunkin Hartley guinea pigs weighing 250 - 300 g were sensitized twice with 10 μg ovalbumin dissolved in aluminium hydroxide (Al(OH)
MeSH term(s)	Allergens ; Animals ; Asthma ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Guinea Pigs ; Inflammation ; Male ; Ovalbumin
Chemical Substances	Allergens ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2021-08-06
Publishing country	Poland
Document type	Journal Article
ZDB-ID	1125221-2
ISSN	1899-1505 ; 0867-5910 ; 0044-6033
ISSN (online)	1899-1505
ISSN	0867-5910 ; 0044-6033
DOI	10.26402/jpp.2021.2.03
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Article ; Online: Effects of controlled physical activity on immune cell phenotype in peripheral blood in prehypertension - studies in preclinical model and randomised crossover study.

Mazur, M / Glodzik, J / Szczepaniak, P / Nosalski, R / Siedlinski, M / Skiba, D / Rewiuk, K / Salakowski, A / Czesnikiewicz-Guzik, M / Grodzicki, T / Guzik, T J / Mikolajczyk, T P

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society

2019 Volume 69, Issue 6

Abstract: Hypertension (HT) is a global public health issue. There are many behavioural risk factors including unhealthy diet, tobacco use and alcohol consumption as well physical inactivity that contribute to the development of high blood pressure (BP) and its ... ...

Abstract	Hypertension (HT) is a global public health issue. There are many behavioural risk factors including unhealthy diet, tobacco use and alcohol consumption as well physical inactivity that contribute to the development of high blood pressure (BP) and its complications. Favourable effect of regular physical activity on treatment or prevention of hypertension by improvement of endothelial function is widely accepted however little is known about its relationship with immune system. Thus, the aim of this study was to assess the role of moderate regular physical activity on immune cell phenotype. T cell and monocyte subsets were characterised in 31 subjects with prehypertension (130 - 139 mmHg systolic and 85 - 89 mmHg diastolic blood pressure) who participated in moderate training (3 times/week) on cyclometers for 3 months in crossover study design. Complementary study was performed in murine model of Ang II-induced hypertension and ten-week-old animals were trained on a treadmill (5 times/week, 1 hour) for 2 weeks before and 1.5 weeks after minipumps implantation. In the context of elevated blood pressure regular physical activity had modest influence on immune cell phenotype. Both in human study and murine model we did not observe effects of applied exercise that can explain the mechanism of BP reduction after short-term regular training. Twelve-weeks regular training did not affect the activation status of T lymphocytes measured as expression of CD69, CD25 and CCR5 in human study. Physical activity resulted in higher expression of adhesion molecule CD11c on CD16+ monocytes (especially CD14 high) without any changes in leukocytes subpopulation counts. Similar results were observed in murine model of hypertension after the training. However the training caused significant decrease of CCR5 and CD25 expressions (measured as a mean fluorescence intensity) on CD8+ T cells infiltrating perivascular adipose tissue. Our studies show modest regulatory influence of moderate training on inflammatory markers in prehypertensive subjects and murine model of Ang II induced hypertension.
MeSH term(s)	Adult ; Animals ; Antigens, CD/immunology ; Biomarkers/metabolism ; Blood Pressure/immunology ; Blood Pressure/physiology ; Cross-Over Studies ; Disease Models, Animal ; Exercise/physiology ; Exercise Test/methods ; Female ; Humans ; Hypertension/immunology ; Hypertension/physiopathology ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes/immunology ; Monocytes/metabolism ; Monocytes/physiology ; Phenotype ; Prehypertension/immunology ; Prehypertension/physiopathology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/physiology
Chemical Substances	Antigens, CD ; Biomarkers
Language	English
Publishing date	2019-03-18
Publishing country	Poland
Document type	Journal Article
ZDB-ID	1125221-2
ISSN	1899-1505 ; 0867-5910 ; 0044-6033
ISSN (online)	1899-1505
ISSN	0867-5910 ; 0044-6033
DOI	10.26402/jpp.2018.6.12
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Article ; Online: Controlled aerobic training improves endothelial function and modifies vascular remodeling in healthy adults with high normal blood pressure.

Glodzik, J / Rewiuk, K / Adamiak, J / Marchewka, J / Salakowski, A / Mazur, M / Brudecki, J / Mikolajczyk, T P / Guzik, T / Aleksander-Szymanowicz, P / Grodzicki, T

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society

2019 Volume 69, Issue 5

Abstract: The aim of the study was to assess endothelial function in adults with high normal blood pressure (HNBP) undergoing controlled aerobic training. The study was conducted among 31 volunteers with HNBP. Subjects underwent supervised cycle ergometer training ...

Abstract	The aim of the study was to assess endothelial function in adults with high normal blood pressure (HNBP) undergoing controlled aerobic training. The study was conducted among 31 volunteers with HNBP. Subjects underwent supervised cycle ergometer training for 12 weeks. Exercise intensity was assessed by monitoring the pulse with intention to keep the heart rate increase within the range of 40% to 65% of the heart rate reserve. The control group consisted of 14 healthy adults, not subjected to any intervention. The control group was examined twice at 12-week intervals (non-exercising time control). Vascular endothelial function was determined by flow-mediated dilation (FMD) and by measuring total nitric oxide products (NOx). The measurement of carotid intima-media complex thickness (IMT) was an indirect method of assessing vascular remodeling. Blood pressure (ABPM method), anthropological parameters and lipid profile were also assessed. There was a significant change in FMD after 3-month training in the study group: the average FMD training was 5.21 ± 2.17%, while after the program FMD increased to 9.46 ± 3.69% (P < 0.001). After training, the NO
MeSH term(s)	Adult ; Blood Pressure/physiology ; Endothelium, Vascular/physiology ; Exercise/physiology ; Female ; Healthy Volunteers ; Humans ; Lipids/blood ; Male ; Middle Aged ; Vascular Remodeling/physiology
Chemical Substances	Lipids
Language	English
Publishing date	2019-01-21
Publishing country	Poland
Document type	Journal Article
ZDB-ID	1125221-2
ISSN	1899-1505 ; 0867-5910 ; 0044-6033
ISSN (online)	1899-1505
ISSN	0867-5910 ; 0044-6033
DOI	10.26402/jpp.2018.5.04
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Article ; Online: Heterogeneity of peripheral blood monocytes, endothelial dysfunction and subclinical atherosclerosis in patients with systemic lupus erythematosus.

Mikołajczyk, T P / Osmenda, G / Batko, B / Wilk, G / Krezelok, M / Skiba, D / Sliwa, T / Pryjma, J R / Guzik, T J

Lupus

2015 Volume 25, Issue 1, Page(s) 18–27

Abstract: Background: Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular morbidity and mortality. SLE patients have increased prevalence of subclinical atherosclerosis, although the mechanisms of this observation remain unclear. ... ...

Abstract	Background: Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular morbidity and mortality. SLE patients have increased prevalence of subclinical atherosclerosis, although the mechanisms of this observation remain unclear. Considering the emerging role of monocytes in atherosclerosis, we aimed to investigate the relationship between subclinical atherosclerosis, endothelial dysfunction and the phenotype of peripheral blood monocytes in SLE patients. Methods: We characterized the phenotype of monocyte subsets defined by the expression of CD14 and CD16 in 42 patients with SLE and 42 non-SLE controls. Using ultrasonography, intima-media thickness (IMT) of carotid arteries and brachial artery flow-mediated dilation (FMD) as well as nitroglycerin-induced dilation (NMD) were assessed. Results: Patients with SLE had significantly, but only modestly, increased IMT when compared with non-SLE controls (median (25th/75th percentile) 0.65 (0.60/0.71) mm vs 0.60 (0.56/0.68) mm; p < 0.05). Importantly, in spite of early atherosclerotic complications in the studied SLE group, marked endothelial dysfunction was observed. CD14dimCD16+proinflammatory cell subpopulation was positively correlated with IMT in SLE patients. This phenomenon was not observed in control individuals. Interestingly, endothelial dysfunction assessed by FMD was not correlated with any of the studied monocyte subsets. Conclusions: Our observations suggest that CD14dimCD16+monocytes are associated with subclinical atherosclerosis in SLE, although the mechanism appears to be independent of endothelial dysfunction.
MeSH term(s)	Adult ; Aged ; Asymptomatic Diseases ; Atherosclerosis/blood ; Atherosclerosis/diagnostic imaging ; Atherosclerosis/etiology ; Atherosclerosis/physiopathology ; Biomarkers/blood ; Brachial Artery/diagnostic imaging ; Brachial Artery/physiopathology ; Carotid Arteries/diagnostic imaging ; Carotid Artery Diseases/blood ; Carotid Artery Diseases/diagnostic imaging ; Carotid Artery Diseases/etiology ; Carotid Intima-Media Thickness ; Case-Control Studies ; Endothelium, Vascular/physiopathology ; Female ; Flow Cytometry ; GPI-Linked Proteins/blood ; Humans ; Lipopolysaccharide Receptors/blood ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/diagnosis ; Male ; Middle Aged ; Monocytes/metabolism ; Phenotype ; Predictive Value of Tests ; Receptors, IgG/blood ; Risk Factors ; Vasodilation ; Young Adult
Chemical Substances	Biomarkers ; FCGR3B protein, human ; GPI-Linked Proteins ; Lipopolysaccharide Receptors ; Receptors, IgG
Language	English
Publishing date	2015-08-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1154407-7
ISSN	1477-0962 ; 0961-2033
ISSN (online)	1477-0962
ISSN	0961-2033
DOI	10.1177/0961203315598014
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Article ; Online: Characterization of the impairment of the uptake of apoptotic polymorphonuclear cells by monocyte subpopulations in systemic lupus erythematosus.

Mikołajczyk, T P / Skiba, D / Batko, B / Krezelok, M / Wilk, G / Osmenda, G / Pryjma, J R / Guzik, T J

Lupus

2014 Volume 23, Issue 13, Page(s) 1358–1369

Abstract: Efficient removal of apoptotic polymorphonuclear leukocytes (PMNs) is an important step in the resolution of inflammation, which protects tissues from the noxious contents of dying cells. While the impairment of apoptotic PMNs removal has been ... ...

Abstract	Efficient removal of apoptotic polymorphonuclear leukocytes (PMNs) is an important step in the resolution of inflammation, which protects tissues from the noxious contents of dying cells. While the impairment of apoptotic PMNs removal has been demonstrated for macrophages in systemic lupus erythematosus (SLE), recent studies show that monocytes are also capable of such phagocytosis, although their involvement in SLE is not clear. Therefore, we characterized phagocytosis of apoptotic PMNs by monocytes in 22 patients with SLE and 22 healthy controls. Using flow cytometry we demonstrate that in SLE peripheral blood monocytes show impaired phagocytosis of autologous apoptotic PMNs, while they efficiently engulf apoptotic PMNs isolated from healthy subjects. Monocytes CD14highCD16+ and CD14dimCD16+ more efficiently interacted with apoptotic neutrophils than CD16- cells both in SLE and healthy subjects. Monocytes in SLE showed modestly decreased expression of CD35 and CD91 and increased expression of T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3); however, these differences were evident mainly in selected subsets of monocytes (CD16+) while defects in phagocytosis were observed in all monocyte subsets. Apoptotic cell-dependent induction of lipopolysaccharide (LPS) stimulated production of anti-inflammatory cytokine IL-10 by peripheral blood mononuclear cells (PBMC) was blunted in SLE while the production of pro-inflammatory cytokine TNF-α was unchanged.
MeSH term(s)	Adult ; Antigens, CD/analysis ; Apoptosis ; Case-Control Studies ; Female ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Interleukin-10/biosynthesis ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Lipopolysaccharide Receptors/analysis ; Lipopolysaccharides/pharmacology ; Low Density Lipoprotein Receptor-Related Protein-1/analysis ; Lupus Erythematosus, Systemic/immunology ; Male ; Membrane Proteins/analysis ; Middle Aged ; Monocytes/chemistry ; Monocytes/immunology ; Neutrophils/physiology ; Phagocytosis ; Receptors, Complement 3b/analysis ; Receptors, IgG/analysis ; Tumor Necrosis Factor-alpha/biosynthesis ; Young Adult
Chemical Substances	Antigens, CD ; HAVCR2 protein, human ; Hepatitis A Virus Cellular Receptor 2 ; Lipopolysaccharide Receptors ; Lipopolysaccharides ; Low Density Lipoprotein Receptor-Related Protein-1 ; Membrane Proteins ; Receptors, Complement 3b ; Receptors, IgG ; Tumor Necrosis Factor-alpha ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2014-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1154407-7
ISSN	1477-0962 ; 0961-2033
ISSN (online)	1477-0962
ISSN	0961-2033
DOI	10.1177/0961203314541316
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Article ; Online: Anti-atherosclerotic effect of the angiotensin 1-7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis.

Skiba, D S / Nosalski, R / Mikolajczyk, T P / Siedlinski, M / Rios, F J / Montezano, A C / Jawien, J / Olszanecki, R / Korbut, R / Czesnikiewicz-Guzik, M / Touyz, R M / Guzik, T J

British journal of pharmacology

2017 Volume 174, Issue 22, Page(s) 4055–4069

Abstract: Background and purpose: Inflammation plays a key role in atherosclerosis. The protective role of angiotensin 1-7 (Ang-(1-7)) in vascular pathologies suggested the therapeutic use of low MW, non-peptide Ang-(1-7) mimetics, such as AVE0991. The mechanisms ...

Abstract	Background and purpose: Inflammation plays a key role in atherosclerosis. The protective role of angiotensin 1-7 (Ang-(1-7)) in vascular pathologies suggested the therapeutic use of low MW, non-peptide Ang-(1-7) mimetics, such as AVE0991. The mechanisms underlying the vaso-protective effects of AVE0991, a Mas receptor agonist, remain to be explored. Experimental approach: We investigated the effects of AVE0991 on the spontaneous atherosclerosis in apolipoprotein E (ApoE)-/- mice, in the context of vascular inflammation and plaque stability. Key results: AVE0991 has significant anti-atherosclerotic properties in ApoE-/- mice and increases plaque stability, by reducing plaque macrophage content, without effects on collagen. Using the descending aorta of chow-fed ApoE-/- mice, before significant atherosclerotic plaque develops, we gained insight to early events in atherosclerosis. Interestingly, perivascular adipose tissue (PVAT) and adventitial infiltration with macrophages and T-cells precedes atherosclerotic plaque or the impairment of endothelium-dependent NO bioavailability (a measure of endothelial function). AVE0991 inhibited perivascular inflammation, by reducing chemokine expression in PVAT and through direct actions on monocytes/macrophages inhibiting their activation, characterized by production of IL-1β, TNF-α, CCL2 and CXCL10, and differentiation to M1 phenotype. Pretreatment with AVE0991 inhibited migration of THP-1 monocytes towards supernatants of activated adipocytes (SW872). Mas receptors were expressed in PVAT and in THP-1 cells in vitro, and the anti-inflammatory effects of AVE0991 were partly Mas dependent. Conclusions and implications: The selective Mas receptor agonist AVE0991 exhibited anti-atherosclerotic and anti-inflammatory actions, affecting monocyte/macrophage differentiation and recruitment to the perivascular space during early stages of atherosclerosis in ApoE-/- mice. Linked articles: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.
MeSH term(s)	Angiotensin I ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Aorta/drug effects ; Aorta/immunology ; Aorta/pathology ; Atherosclerosis/drug therapy ; Atherosclerosis/immunology ; Atherosclerosis/pathology ; Cell Line ; Cell Line, Tumor ; Cytokines/genetics ; Female ; Humans ; Imidazoles/therapeutic use ; Leukocytes/drug effects ; Leukocytes/immunology ; Macrophages/drug effects ; Macrophages/immunology ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Peptide Fragments ; Plaque, Atherosclerotic ; Proto-Oncogene Mas ; Proto-Oncogene Proteins/agonists ; Receptors, G-Protein-Coupled/agonists
Chemical Substances	AVE 0991 ; Anti-Inflammatory Agents ; Cytokines ; Imidazoles ; Peptide Fragments ; Proto-Oncogene Mas ; Proto-Oncogene Proteins ; Receptors, G-Protein-Coupled ; Angiotensin I (9041-90-1) ; angiotensin I (1-7) (IJ3FUK8MOF)
Language	English
Publishing date	2017-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.13685
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