Continuous therapy with transdermal nitroglycerin does not affect biomarkers of vascular inflammation and injury in healthy volunteers

2009 ◽  
Vol 87 (6) ◽  
pp. 455-459 ◽  
Author(s):  
George R. Thomas ◽  
Jonathan M. DiFabio ◽  
Tommaso Gori ◽  
David J.A. Jenkins ◽  
John D. Parker
Keyword(s):  
Healthy Volunteers ◽  
Vascular Inflammation ◽  
Venous Blood ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Continuous Exposure ◽  
Intercellular Adhesion Molecule 1 ◽  
Continuous Therapy ◽  
Factor Α ◽  
Dimethyl Arginine

Continuous exposure to nitroglycerin (GTN) results in development of tolerance and is associated with increased free radical production and abnormal endothelial function. Elevated plasma biomarkers of inflammation have been shown to be associated with endothelial dysfunction in most cardiovascular conditions. It remains unclear whether exposure to GTN is also associated with increased biomarkers of endothelial and vascular injury or vascular inflammation. In an investigator-blind study, a total of 28 healthy volunteers were randomized to continuous therapy with GTN (0.6 mg/h 24 h/day for 7 days) or no therapy. Venous blood was collected on day 0 and day 7. Plasma levels of markers such as asymmetric dimethyl-arginine (ADMA), human soluble P-selectin, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, and oxidized low-density lipoproteins were measured. The levels of blood markers on day 0 were similar in the control and GTN-treated groups. After 7 days of GTN exposure, there were no significant changes in the different markers of vascular inflammation and injury either in the GTN or control group (all p > 0.5). The present study documents that prolonged continuous therapy with transdermal GTN therapy is not associated with changes in markers of vascular inflammation and injury.

scholarly journals Endothelial Dysfunction and Thrombosis in Patients With COVID-19—Brief Report

2020 ◽  
Vol 40 (10) ◽  
pp. 2404-2407 ◽  
Author(s):  
Seigo Nagashima ◽  
Monalisa Castilho Mendes ◽  
Ana Paula Camargo Martins ◽  
Nícolas Henrique Borges ◽  
Thiago Mateus Godoy ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Influenza A ◽  
Endothelial Activation ◽  
Tissue Expression ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Il Interleukin ◽  
Factor Α ◽  
And Control

Objective: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. Conclusions: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff’s efforts to avoid fatal outcomes. One of the health professionals’ goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.

Can Cytokines be used as an Activation Marker in Rheumatoid Arthritis?

2020 ◽  
Vol 20 ◽  
Author(s):  
Fatih Öner Kaya ◽  
Yeşim Ceylaner ◽  
Belkız Öngen İpek ◽  
Zeynep Güneş Özünal ◽  
Gülbüz Sezgin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Volunteers ◽  
Venous Blood ◽  
Cross Sectional Study ◽  
Joint Disease ◽  
Control Group ◽  
Cross Sectional ◽  
Positive Correlation ◽  
Das 28 ◽  
Tnf Α

Aims: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines takes an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. Background: RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as a primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. Objective: In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. Methods: This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. Results: RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA according to RA in remission (p=0.03). DAS-28 was significantly high in active RA according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). Conclusion: TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.

scholarly journals Influence of Glutamine on Intestinal Inflammatory Response, Mucosa Structure Alterations and Apoptosis following Traumatic Brain Injury in Rats

2007 ◽  
Vol 35 (5) ◽  
pp. 644-656 ◽  
Author(s):  
D Feng ◽  
W Xu ◽  
G Chen ◽  
C Hang ◽  
H Gao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Intestinal Inflammation ◽  
Glutamine Supplementation ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tissue Samples ◽  
Weight Drop ◽  
Factor Α

Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes and apoptosis in the intestine. Glutamine has been shown to reduce bacterial translocation and maintain intestine mucosal integrity, but its effects on the inflammatory response, structural alterations and apoptosis in intestinal mucosa following TBI have not been previously investigated. Using the weight-drop method, a right parietal cortical contusion was induced in rats and, for the next 5 days, they were fed either chow alone or chow mixed with glutamine. Intestinal tissue samples were then removed for analysis. Following TBI, glutamine supplementation was found to: decrease intestinal concentrations of interleukin (IL) −1β, tumour necrosis factor-α (TNF-α) and IL-6; downregulate intercellular adhesion molecule-1 (ICAM-1) expression; attenuate TBI-induced damage to the intestine structure; and reduce apoptosis. These results suggest that post-TBI glutamine administration could suppress intestinal inflammation, protect intestinal mucosal structure and reduce mucosal apoptosis.

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

2018 ◽  
Vol 74 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Joanna J. Samulak ◽  
Angelika K. Sawicka ◽  
Dace Hartmane ◽  
Solveiga Grinberga ◽  
Osvalds Pugovics ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Adhesion Molecule ◽  
Serum Proteins ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Intercellular Adhesion Molecule ◽  
Carnitine Supplementation ◽  
Intercellular Adhesion Molecule 1 ◽  
Factor Α

Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that ­although oral L-carnitine supplementation significantly ­increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

scholarly journals Inhibition of PAR1 attenuates meningeal macrophage activation and vascular inflammation in a rat model of thrombin-induced hydrocephalus

2019 ◽  
Author(s):  
Xiaodi Hao ◽  
Xianghua Ye ◽  
Dan Shen ◽  
Chensheng Le ◽  
Lusha Tong ◽  
...  
Keyword(s):  
Subarachnoid Space ◽  
Vascular Inflammation ◽  
Intercellular Adhesion Molecule ◽  
Intraventricular Injection ◽  
Thrombin Injection ◽  
Intercellular Adhesion Molecule 1 ◽  
Neuron Loss ◽  
Meningeal Inflammation ◽  
M1 Polarization ◽  
Pro Inflammatory Cytokines

Abstract Background and Purpose— Our previous studies demonstrated that intraventricular injection of thrombin could induce hydrocephalus. The inflammation of subarachnoid space plays a key role in hydrocephalus. As thrombin, inducing coagulation, could contribute to inflammation, its effects on subarachnoid space have not been well studied. Macrophagic dysfunction may contribute to this course. However, the mechanisms that how thrombin affects macrophage in subarachnoid space have not been illustrated. Our aim was to explore the possible role that macrophage played in thrombin-induced meningeal inflammation, and to furtherly understand its contribution during thrombin-induced hydrocephalus. Methods— There were two parts in this study. Firstly, rats had an intraventricular injection of saline or thrombin. Secondly, rats received thrombin injection with vehicle or PAR1 antagonist treatment. Immunofluorescence staining was applied to observe the activation of meningeal macrophage and the expression of NeuN in the cortex. Meanwhile, the expression of intercellular adhesion molecule 1 (ICAM1) in meningeal vessels were tested to detect the vascular inflammation. Western blot was applied to measure the secretion of pro-inflammatory cytokines (IL-1β and IFNγ). Results— Our results demonstrated that intraventricular injection of thrombin caused significant activation of meningeal macrophages, vascular inflammation, and neuron loss. Inhibition of PAR1 pathway attenuated the M1 polarization of meningeal macrophage, reduced the inflammatory infiltrations and prevented the neuron loss, as well as hydrocephalus after thrombin injection. Conclusions— Clinically available PAR1 antagonists may offer a novel therapeutic approach candidate for the prevention or the management of inflammation in hemorrhage-induced hydrocephalus.

scholarly journals Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Guanrong Wu ◽  
Baoyi Liu ◽  
Qiaowei Wu ◽  
Changting Tang ◽  
Zijing Du ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Proliferative Diabetic Retinopathy ◽  
Fasting Blood Glucose ◽  
Intercellular Adhesion Molecule ◽  
Inflammatory Factors ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Vitreous Fluid ◽  
Inflammation Mediators

Purpose: To investigate the expression of various angiogenesis and inflammation mediators in the vitreous fluid of eyes with proliferative diabetic retinopathy (PDR).Methods: A total of 38 eyes with PDR and 37 control eyes were included. Vitreous fluid was collected during vitrectomy. Vitreous levels of colony stimulating factor-1 receptor (CSF-1R), syndecan-1, placental growth factor (PIGF), and angiopoietin-like protein 4 (ANGPTL-4) were measured by multiplex immunoassay. Vitreous levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were measured by cytometric beads array. Levels of these mediators were compared between the PDR and control eyes. Correlations between levels of different mediators and between these mediators and kidney function metrics in the PDR group were also analyzed.Results: Vitreous levels of syndecan-1, PIGF, ANGPTL-4, VEGF, and IL-8 were significantly higher in the PDR group compared to the control group (all p < 0.05). Levels of VEGF were significantly correlated with levels of syndecan-1, PIGF, and ANGPTL-4 (r = 0.370 to 0.497, all p < 0.05). Significant positive correlations were detected between levels of any two of the following mediators including syndecan-1, PIGF, ANGPTL-4, and IL-8 (r = 0.370 to 0.906, all p < 0.05). Apart from VEGF, levels of these mediators were positively correlated with serum creatinine and blood urea nitrogen (r = 0.328 to 0.638, all p < 0.05), and negatively correlated with fasting blood glucose and estimated glomerular filtration rate (r = −0.325 to −0.603, all p < 0.05).Conclusions: Correlations between different angiogenesis and inflammation mediators were observed in eyes with PDR, suggesting cross-talks of different angiogenesis and inflammation pathways in the pathogenesis of PDR. The levels of angiogenesis and inflammation in PDR are correlated with kidney damage, indicating possible common pathways in diabetic retinopathy and nephropathy.

Hepatic macrophage accumulation with aging: cause for concern?

2021 ◽  
Author(s):  
Steven A. Bloomer ◽  
Eric Moyer
Keyword(s):  
Healthy Aging ◽  
Intercellular Adhesion Molecule ◽  
Low Grade ◽  
Intercellular Adhesion Molecule 1 ◽  
Age Related ◽  
Hepatic Macrophages ◽  
Liver Macrophage ◽  
Factor Α ◽  
Low Grade Inflammation ◽  
Hepatic Macrophage

Aging is associated with chronic, low-grade inflammation that adversely affects physiological function. The liver regulates systemic inflammation; it is a source of cytokine production and also scavenges bacteria from the portal circulation to prevent infection of other organs. The cells with primary roles in these functions, hepatic macrophages, become more numerous in the liver with "normal" aging (i.e. in the absence of disease). Here we demonstrate evidence and potential mechanisms for this phenomenon, which include augmented tumor necrosis factor-α (TNFα) and intercellular adhesion molecule-1 (ICAM-1) expression in the liver. Also, we discuss how an age-related impairment in autophagy within macrophages leads to a pro-oxidative state and ensuing production of pro-inflammatory cytokines, particularly interleukin 6 (IL-6). Given that the liver is a rich source of macrophages, we posit that it represents a major source of the elevated systemic IL-6 observed with aging, which is associated with physiological dysfunction. Testing a causal role for liver macrophage production of IL-6 during aging remains a challenge, yet interventions that have targeted macrophages and/or IL-6 have demonstrated promise in treating age-related diseases. These studies have demonstrated an age-related, deleterious reprogramming of macrophage function, which worsens pathology. Therefore, hepatic macrophage accrual is indeed a cause for concern, and therapies that attenuate the aged phenotype of macrophages will likely prove useful in promoting healthy aging.

The Role of Oxidative Stress, Inflammation, and Advanced Glycation End Product in Skin Manifestations of Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Lili Legiawati
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Skin Disorders ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
High Level ◽  
Factor Α

: Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non-T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen-activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

Exercise suppresses macrophage antigen presentation

1999 ◽  
Vol 87 (6) ◽  
pp. 2253-2258 ◽  
Author(s):  
M. A. Ceddia ◽  
J. A. Woods
Keyword(s):  
T Cells ◽  
Antigen Presentation ◽  
Home Cage ◽  
Interleukin 2 ◽  
Exhaustive Exercise ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Cage Control ◽  
Wide Range

This study determined the effects of exercise on the ability of macrophages (Mφ) to present antigen to T cells. Pathogen-free male Balb/c mice (8 ± 2 wk of age) were randomly assigned to either home cage control, moderate exercise (Mod; 18 m/min, 5% grade, 0.5 h/day), exhaustive exercise (Exh, 18–30 m/min, 3 h/day), or treadmill control groups. The mice underwent treatments for 4 days during peritoneal thioglycolate inflammation. Peritoneal Mφ were harvested, purified, and incubated with chicken ovalbumin (C-OVA; 0–10 mg/ml) for 18 h. Mφ were then cocultured with C-OVA-specific T cells for 48 h, and the supernatants were analyzed via ELISA for interleukin-2 as an indication of Mφ antigen presentation (AP). Exh exhibited suppressed (∼25–34%) Mφ AP across a wide range of C-OVA doses when measured immediately, 3, and 24 h postexercise. In contrast, Mod had reduced Mφ AP only at 3 h postexercise. Mφ AP was also lower in the treadmill control (4–27%) compared with the home cage control group, but was significantly higher than Exh. The reduction in Mφ AP was not due to exercise-induced differences in Mφ number, percentage, or expression of intercellular adhesion molecule-1, B7–2, or major histocompatability complex II, molecules important in AP. In conclusion, our data lend evidence that may help explain the increased incidence of infection observed after prolonged exhaustive exercise or overtraining.

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