Evidence for injurious effect of cocaethylene in human microvascular endothelial cells

Tacker, Danyel H.; Okorodudu, Anthony O.

doi:10.1016/j.cccn.2004.02.031

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…This increase was significantly greater than the effects of serum stimulation but intermediate compared with maximal stimulation of p38 MAPK phosphorylation in HMEC-1 by LPS from S. typhosa. This finding is largely substantiated by our previous studies (33 ) and by other reports of observed endothelial permeability increases associated with p38 MAPK phosphorylation (31,40,41 ).…”

Section: Discussionsupporting

confidence: 87%

“…We postulate that CE affects the vascular endothelium, and the resulting systemic disturbances in vascular function commonly lead to tissue ischemia and systemic diseases. Previously, we demonstrated that a lethal concentration of CE leads to vascular endothelial dysfunction via alterations in monolayer permeability (33 ). We began elucidating the mechanism by demonstrating that the same concentration of CE alters endothelial monolayer resistance, intracellular calcium ion flux, and the generation of inositol 1,4,5-trisphosphate (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Such endothelial alterations could be implicated in the mechanisms of CE-associated vascular toxicity. We have demonstrated that exposure to 1 mmol/L CE alters the morphology of human microvascular endothelial cells (HMEC-1) without altering monolayer viability or inducing overt cytotoxicity (33 ). The morphologic change observed was associated with decreased monolayer electrical resistance, possibly modulated by an observed increase in HMEC-1 cellular calcium load and inositol trisphosphate generation.…”

mentioning

confidence: 94%

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Cocaethylene Affects Human Microvascular Endothelial Cell p38 Mitogen-Activated Protein Kinase Activation and Nuclear Factor-κB DNA-Binding Activity

Tacker

Herzog

Okorodudu³

2006

Clinical Chemistry

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Background: Cocaethylene (CE) is known to increase the permeability of human microvascular endothelial cell monolayers. The molecular mechanism underlying this increase may involve calcium-modulated signaling pathways such as the p38 mitogen-activated protein kinase (p38 MAPK) and the nuclear factor-B (NF-B) family of transcription factors. The hypothesis of this study was that CE-mediated endothelial permeability change may be mediated by the p38 MAPK and consequently NF-B dimers. Methods: We used sandwich ELISA to detect phosphorylated p38 MAPK in the cell line human microvascular endothelial cell 1 (HMEC-1) after treatment with 1 mmol/L CE. We used electrophoretic mobility shift assay to detect changes in NF-B dimers present in HMEC-1 and their DNA-binding activity after treatment with CE. Lipopolysaccharide (LPS) from Salmonella typhosa was used as a positive control for all experiments. Results: Treatment with CE and LPS had similar effects on HMEC-1 p38 MAPK phosphorylation and NF-B DNA-binding activity. Both treatments increased the phosphorylation of p38 MAPK, consistent with activation of proinflammatory cell signaling. Treatment of HMEC-1 with CE decreased DNA binding of both the RelA/p50 and p50/p50 dimers of the NF-B transcription factor family, whereas treatment with LPS decreased and then increased the DNA binding of these dimers. Conclusion: In addition to increasing HMEC-1 monolayer permeability, CE also alters transcription factor

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

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Cocaethylene Affects Human Microvascular Endothelial Cell p38 Mitogen-Activated Protein Kinase Activation and Nuclear Factor-κB DNA-Binding Activity

Tacker

Herzog

Okorodudu³

2006

Clinical Chemistry

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“…Cocaine has been shown to synergistically enhance the pathologic processes induced by HIV infection [23–25]. Cocaine is also known to induce oxidative stress, tight junction disruption, endothelial cell inflammation dysfunction, and loss of BBB integrity [26–28]. Hence cocaine use in this patient may have precipitated PRES by itself or in conjunction with HIV infection.…”

Section: Discussionmentioning

confidence: 99%

An atypical subacute presentation of posterior reversible encephalopathy syndrome

Bazuaye-Ekwuyasi

Chow

Schmalzle

2017

Journal of Community Hospital Internal Medicine Perspectives

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Posterior reversible encephalopathy syndrome (PRES) characteristically presents with rapid onset of headache, seizure, encephalopathy, and visual changes, along with evidence of parieto-occipital vasogenic edema on magnetic resonance imaging. We describe the case of a 41-year-old female with a protracted presentation of two of the four classic PRES symptoms, which were not immediately recognized as PRES due to the presence of multiple other comorbidities and reasons for encephalopathy. This case highlights the possibility of atypical presentations of PRES and the diagnostic challenges in making this clinical diagnosis when competing diagnoses are present.

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“…Cocaethylene shares the same molecular targets as cocaine [68] and because of its prolonged half life (cocaethylene, 2 -4 h vs. cocaine which is 30 -90 min) it may lead to persistent toxicity [69,70]. Cocaethylene inhibits the re-uptake of dopamine at the synaptic cleft [66,68] and enhances microvascular permeability [71]. Our experiments demonstrated that cocaethylene is 10-fold more potent than cocaine in decreasing peak intracellular calcium and myofilament responsiveness in ferret cardiac muscles to produce a negative inotropic effect [67].…”

Section: Cocaine and Ethanolmentioning

confidence: 99%

Vascular Toxicity of Cocaine

Bansal¹,

Morgan²

2009

VDP

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Cocaine acts on the vascular system by a number of mechanisms including monoamine re-uptake inhibition, local anesthesia, anti-cholinergic activity, alpha-adrenergic stimulation, regulation of various vasoconstrictor and vasodilator agents and promotion of prothrombotic state. These effects lead to a number of clinical syndromes via vasoconstriction, platelet activation, thrombus formation and early atherosclerosis in almost every organ of the body. Many of these effects may be under appreciated. Furthermore, cocaine is commonly associated with the use of tobacco and alcohol which can lead to superadditive effects and/or prolonged toxicity.

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Evidence for injurious effect of cocaethylene in human microvascular endothelial cells

Cited by 16 publications

References 32 publications

Cocaethylene Affects Human Microvascular Endothelial Cell p38 Mitogen-Activated Protein Kinase Activation and Nuclear Factor-κB DNA-Binding Activity

Cocaethylene Affects Human Microvascular Endothelial Cell p38 Mitogen-Activated Protein Kinase Activation and Nuclear Factor-κB DNA-Binding Activity

An atypical subacute presentation of posterior reversible encephalopathy syndrome

Vascular Toxicity of Cocaine

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