Search results for " Type II"
showing 10 items of 542 documents
iNOS-derived nitric oxide mediates the increase in TFF2 expression associated with gastric damage: role of HIF-1.
2009
Trefoil (TFF) peptides are involved in gastrointestinal mucosal restitution. An hypoxia inducible factor 1 (HIF-1)-dependent induction of TFF genes has been reported in gastric epithelial cells. Nitric oxide (NO) is associated with mucosal damage and modulates HIF-1 activity. The aim of the present study was to analyze the role of iNOS-derived NO in HIF-1alpha stabilization and TFF gene expression in damaged gastric mucosa. Aspirin caused gastric injury that peaked 6 h after dosing and returned to normality at 24 h. iNOS mRNA expression occurs in the corpus in parallel with damage. Blockade of iNOS activity did not modify gastric lesions induced by aspirin but delayed mucosal healing. Aspir…
Inhibition of iNOS activity by 1400W decreases glutamate release and ameliorates stroke outcome after experimental ischemia
2005
Background and purpose. It has been shown that the reversed operation of glutamate transporters when ATP levels fall accounts for most glutamate release induced by severe cerebral ischemia. Nitric oxide (NO) is formed after ischemia and causes ATP depletion. Our purpose is to test if NO release from inducible NO synthase (iNOS) after stroke may cause a delayed glutamate release due to ATP depletion that might underlie progression of the ischemic infarct. We have studied the effect of the highly selective inhibitor of iNOS activity 1400W on brain ATP levels, extracellular glutamate, and stroke outcome after transient focal cerebral ischemia in rats. Methods. To induce focal ischemia, the mid…
Effect of autologous blood transfusion on cerebral cytokine expression.
2011
BACKGROUND: Autologous blood transfusion (ABT), for example, by means of cell saver equipment, is used to reduce the need for allogenic blood transfusion in patients with high perioperative blood loss. This study investigated the effect of blood/extracorporal surface interaction during withdrawal and retransfusion of shed autologous blood on cerebral inflammation in rats. Rats subjected to hypotension with cerebral ischemia served as positive controls. METHODS: Eighty-eight male Sprague-Dawley rats were anesthetized with sevoflurane, instrumented, and randomly assigned to the following groups: sham-operation (SHAM), autologous blood withdrawal/transfusion only (ABT), or bilateral carotid ar…
Phytochemical and pharmacological studies on the acetonic extract of Marrubium globosum ssp. libanoticum
2006
A new natural labdane diterpene, marrulibanoside, was isolated from the acetonic extract of aerial parts of M. globosum Montbr. et Auch. ex Benth. ssp. libanoticum Boiss. (Lamiaceae). Its structure was determined by spectroscopic methods such as 1D and 2D NMR and mass spectrometry. Pharmacological studies have shown that the extract of M. globosum exerts anti-inflammatory effects in the rat paw oedema induced by carrageenin resulting in reduced paw swelling. This activity, which seems due to marrulibanoside, is a consequence of iNOS and COX-2 activities inhibition.
Role of endothelial nitric oxide in pulmonary and systemic arteries during hypoxia
2014
Abstract Our aim was to investigate the role played by endothelial nitric oxide (NO) during acute vascular response to hypoxia, as a modulator of both vascular tone (through guanylate cyclase (sGC) activation) and mitochondrial O2 consumption (through competitive inhibition of cytochrome-c-oxydase (CcO)). Organ bath experiments were performed and O2 consumption (Clark electrode) was determined in isolated aorta, mesenteric and pulmonary arteries of rats and eNOS-knockout mice. All pre-contracted vessels exhibited a triphasic hypoxic response consisting of an initial transient contraction (not observed in vessels from eNOS-knockout mice) followed by relaxation and subsequent sustained contra…
Midostaurin upregulates eNOS gene expression and preserves eNOS function in the microcirculation of the mouse
2005
Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is a powerful vasodilator and possesses vasoprotective effects. Therefore, augmentation of eNOS expression and -activity by pharmacological means could provide protection against cardiovascular disease. However, this concept has been questioned recently, because in several disease models, eNOS upregulation was associated with a dysfunctional enzyme (referred to as eNOS uncoupling). In contrast, the present study demonstrates that an eNOS gene expression-enhancing compound with additional protein kinase C (PKC) inhibitory properties can upregulate eNOS while preserving its enzymatic function. Apolipoprotein E-knockout mice were tr…
Oncogene-driven intrinsic inflammation induces leukocyte production of tumor necrosis factor that critically contributes to mammary carcinogenesis.
2010
Abstract Oncogene activation promotes an intrinsic inflammatory pathway that is crucial for cancer development. Here, we have investigated the actual effect of the inflammatory cytokine tumor necrosis factor (TNF) on the natural history of spontaneous mammary cancer in the HER2/neuT (NeuT) transgenic mouse model. Bone marrow transplantation from TNF knockout mice into NeuT recipients significantly impaired tumor growth, indicating that the source of TNF fostering tumor development was of bone marrow origin. We show that the absence of leukocyte-derived TNF disarranged the tumor vasculature, which lacked pericyte coverage and structural integrity, leading to diffuse vascular hemorrhage and s…
Nitric oxide-mediated inhibition of androgen receptor activity: possible implications for prostate cancer progression.
2006
Chronic inflammation increases the risk of cancer and many cancers, including prostate cancer, arise at sites of chronic inflammation. Inducible nitric oxide synthase (iNOS) is an enzyme dominantly expressed during inflammatory reactions. Although synthesis of high amounts of nitric oxide (NO) by iNOS has been demonstrated in pathophysiological processes, such as acute or chronic inflammation, autoimmune diseases or tumorigenesis, the role of iNOS activity in most of these diseases is poorly understood. Analysing prostate cancer biopsies by immunohistochemistry we found iNOS protein expression in tumor cells strongly paralleled by nitrotyrosine suggesting that iNOS is fully active. In vitro…
Gene therapy with iNOS enhances regional contractility and reduces delayed contrast enhancement in a model of postischemic congestive heart failure
2012
Aims: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. Methods: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. Results: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. Wall thickness at end-…
Neuroprotective properties of mildronate, a mitochondria-targeted small molecule.
2010
Mildronate, a representative of the aza-butyrobetaine class of drugs with proven cardioprotective efficacy, was recently found to prevent dysfunction of complex I in rat liver mitochondria. The present study demonstrates that mildronate also acts as a neuroprotective agent. In a mouse model of azidothymidine (anti-HIV drug) neurotoxicity, mildronate reduced the azidothymidine-induced alterations in mouse brain tissue: it normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and iNOS expression assessed by quantitative and semi-quantitative analysis. Mildronate also normalized the changes in cytochrome c oxidase (COX) expression, reduced the expression of glia…