88 research outputs found
Retinoic acid upregulates β<sub>1</sub>-integrin in vascular smooth muscle cells and alters adhesion to fibronectin
Retinoic acid has an established physiological role in differentiation, development, and cellular growth. This study investigated the action of all- trans retinoic acid (ATRA) on vascular integrins, cell-surface receptors that control growth and remodeling of blood vessels. The β1-integrin subunit mRNA and protein was induced after treatment with ATRA in two different rat vascular smooth muscle cell lines. To relate this result to the in vivo state, the aortas from adult rats fed with therapeutic doses of ATRA were examined for β1-integrin protein. A significant upregulation of the integrin subunit was observed in vivo. To assess if this increase contributed to physiological changes in cellular function, cells treated with ATRA were tested for alterations in adhesion to extracellular matrix proteins. The cells exposed to the retinoid were seen to adhere more strongly to fibronectin, via the β1-integrin. These results showed that modulation of vascular integrins by ATRA in adult rats contributes to functional changes that can cause remodeling of blood vessels.</jats:p
Advances in Mitigation of Injuries from Radiological Terrorism or Nuclear Accidents (Review Paper)
A program to deal with the medical consequences of a radiological terrorism incident or a nuclear accident requires three principal components: (i) the technology to rapidly determine the radiation doses received by a large number of people, (ii) methods for alleviating acute hematological radiation injuries, and (iii) approved drugs for mitigation of chronic radiation injuries. Laboratory studies have shown that all these needs can be met theoretically. However, moving from the existing laboratory studies to a deployed program is not easy. The work that still needs to be done is expensive and time-consuming, and the move from the laboratory to the field may also face severe regulatory barriers.Defence Science Journal, 2011, 61(2), pp.99-104, DOI:http://dx.doi.org/10.14429/dsj.61.82
Radiation damage to the lung: Mitigation by angiotensin-converting enzyme (ACE) inhibitors
Lipopolysaccharide-induced cytokine expression in alveolar epithelial cells: Role of PKCζ-mediated p47phox phosphorylation
Mechanisms underlying increased reactivity of pulmonary arteries contralateral to a localized high-flow anastomosis
ObjectivesOur model of a systemic–pulmonary shunt exhibits enhanced reactivity of pulmonary arteries contralateral to a localized shunt between the left lower lobe pulmonary artery and aorta relative to those of ipsilateral or control pulmonary arteries 48 hours after anastomosis. We examined the contribution of nitric oxide, cyclooxygenase, lipoxygenase, or cytochrome P450 production to mediating this enhanced reactivity.MethodsWe created a surgical end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta. Forty-eight hours later, we tested tension of pulmonary artery rings from the right and left lower lobes for contraction to the thromboxane mimetic U46619 in the presence of vehicle or inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450, or lipoxygenase. Western blots of pulmonary artery homogenates were probed for endothelial nitric oxide synthase or isoforms metabolizing arachidonic acid. Eicosanoid products from intact pulmonary artery rings were detected using labeled arachidonic acid and high-performance liquid chromatography separation.ResultsEnhanced reactivity of unshunted right pulmonary arteries over that of left pulmonary arteries from high-flow hosts was not eliminated by inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450. Treatment with 2 different lipoxygenase inhibitors, nordihydroguaiaretic acid and cinnamyl-3,4-dihydroxy-α-cyanocinnamate, closed the difference in contractility of shunted and unshunted pulmonary arteries. Pulmonary arteries contralateral to shunts metabolized arachidonic acid to 12-hydroxyeicosatetraenoic acid in greater quantities than analogous pulmonary arteries from the experimental left or control pulmonary arteries.ConclusionsForty-eight hours after anastomosis, enhanced reactivity of contralateral pulmonary arteries is attributable in part to increased lipoxygenase products as opposed to nitric oxide or other eicosanoid products
The Role of TLR4 and HMGB1 in the Ischemia/Reperfusion-Mediated Mitochondrial Dysfunction
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