Difference in PaO/FiO between high-flow nasal cannula and Venturi mask in hypoxemic COVID-19 patients.

The ratio between arterial blood partial pressure of oxygen and fraction of inspired oxygen (PaO/FiO) was largely used for grading and managing the respiratory failure in non-mechanically ventilated COVID-19. In these patients, the assessment of the true FiO in the inspired mixture may be difficult with consequent inaccuracies in PaO/FiO assessment. In 30 severe COVID-19 patients, we observed that PaO/FiO values measured immediately before and after the transition from high-flow nasal cannula (HFNC) to one commercially available Venturi mask O therapy were similar (bias mean value 0, standard deviation 23 mmHg).

Prevention of bleomycin-induced lung fibrosis in mice by a novel approach of parallel inhibition of cyclooxygenase and nitric-oxide donation using NCX 466, a prototype cyclooxygenase inhibitor and nitric-oxide donor.

Cyclooxygenase (COX)-inhibiting nitric oxide (NO) donors (CINODs) are designed to inhibit COX-1 and COX-2 while releasing NO. COX inhibition is responsible for anti-inflammatory and pain-relieving effects, whereas NO donation can improve microcirculation and exert anti-inflammatory and antioxidant actions. In an in vivo mouse model of bleomycin-induced lung fibrosis, we evaluated whether a prototype CINOD compound, (S)-(5S)-5,6-bis(nitrooxy)hexyl)2-(6-methoxynaphthalen-2-yl)propanoate (NCX 466), may show an advantage over naproxen, its congener drug not releasing NO.

Regulation of lentivirus neurovirulence by lipopolysaccharide conditioning: suppression of CXCL10 in the brain by IL-10.

Lentivirus infections including HIV and feline immunodeficiency virus (FIV) cause neurovirulence, which is largely mediated by innate immunity. To investigate the interactions between neurovirulence and repeated conditioning by innate immune activation, models of lentivirus infection were exposed to LPS. Gene expression in HIV-infected (HIV+) and control (HIV-) patient brains was compared by real time RT-PCR and immunocytochemistry.

Cyclooxygenase-inhibiting nitric oxide donators for osteoarthritis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly used medications for the treatment of the symptoms of many chronic inflammatory diseases, including osteoarthritis. Unfortunately, the toxicity of NSAIDs substantially limits their long-term use. Some newer NSAIDs, namely selective cyclooxygenase (COX)-2 inhibitors, exhibit greater gastrointestinal safety, and concomitant use of anti-secretory drugs can also reduce NSAID-induced gastropathy.

Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione.

Matrix metalloproteinase-2 (MMP-2) has emerged as a key protease in various pathologies associated with oxidative stress, including myocardial ischemia-reperfusion, heart failure or inflammation. Peroxynitrite (ONOO(-)), an important effector of oxidative stress, was reported to activate some full length MMP zymogens, particularly in the presence of glutathione (GSH), but whether this occurs for MMP-2 is unknown. Treating MMP-2 zymogen with ONOO(-) resulted in a concentration-dependent regulation of MMP-2, with 0.

The role of matrix metalloproteinase inhibitors in ischemia-reperfusion injury in the liver.

Liver ischemia-reperfusion injury is characterized by cell necrosis and apoptosis and by profound modifications in the extracellular matrix (ECM). During the complex series of events that take place both during ischemia and when normal blood flow is restored (reperfusion), a concerted regulation of release and activation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) mainly by stellate cells, Kupffer cells and inflammatory cells leads first to endothelial cell injury and subsequent infiltration of neutrophils into the wounded area. Later, MMP activation causes degradation of extracellular matrix components of the liver, mainly collagen and fibronectin, altering tissue architecture.

The involvement of superoxide and iNOS-derived NO in cardiac dysfunction induced by pro-inflammatory cytokines.

Pro-inflammatory cytokines have been shown to depress myocardial mechanical function by enhancing peroxynitrite generation in the heart. The contribution of NO synthesized by different NOS isoforms, as well as the contribution of superoxide to this mechanism are still not clear. Isolated working hearts of iNOS(-/-) and wildtype mice were perfused for 120 min in the presence or absence of a mixture of pro-inflammatory cytokines (IL-1beta, TNF-alpha, and IFN-gamma).

Inhibition of endogenous nitric oxide in the heart enhances matrix metalloproteinase-2 release.

Matrix metalloproteinase (MMP) activity is upregulated in pathologies such as atherosclerosis during which endogenous nitric oxide (NO) biosynthesis is reduced. Diminished levels of NO, an antioxidant species, may result in higher oxidative stress. Oxidants are capable of activating MMPs from their zymogen forms.

KB130015, a new amiodarone derivative with multiple effects on cardiac ion channels.

KB130015 (KB015), a new drug structurally related to amiodarone, has been proposed to have antiarrhythmic properties. In contrast to amiodarone, KB015 markedly slows the kinetics of inactivation of Na(+) channels by enhancing concentration-dependently (K(0.5) asymptotically equal to 2 microM) a slow-inactivating I(Na) component (tau(slow) asymptotically equal to 50 ms) at the expense of the normal, fast-inactivating component (tau(fast) asymptotically equal to 2 to 3 ms).

Slowing of the inactivation of cardiac voltage-dependent sodium channels by the amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015).

-Methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015 or KB) is a new drug, structurally related to amiodarone and to thyroid hormones. Its effects on cardiac voltage-dependent Na+ current (I Na) were studied in pig single ventricular myocytes at 22 degrees C using the whole-cell (with [Na+]i = [Na+]o = 10 mM) and cell-attached patch-clamp techniques. KB markedly slowed I Na inactivation, due to the development of a slow-inactivating component (tau slow approximately equal 50 ms) at the expense of the normal, fast-inactivating component (tau fast approximately equal 2-3 ms).

The Cycloxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of focal ischemia in the rat.

Focal ischemia was induced in the fronto-parietal region of rat brain, by injection of Rose Bengal, followed by light activation. Focal ischemia was accompanied by formation of PGD(2) peaking 60-90 min post irradiation and declining thereafter. Increased Cycloxygenase-2 (COX-2) expression was also observed.

Estrogen prevents the lipopolysaccharide-induced inflammatory response in microglia.

After neuronal injury and in several neurodegenerative diseases, activated microglia secrete proinflammatory molecules that can contribute to the progressive neural damage. The recent demonstration of a protective role of estrogen in neurodegenerative disorders in humans and experimental animal models led us to investigate whether this hormone regulates the inflammatory response in the CNS. We here show that estrogen exerts an anti-inflammatory activity on primary cultures of rat microglia, as suggested by the blockage of the phenotypic conversion associated with activation and by the prevention of lipopolysaccharide-induced production of inflammatory mediators: inducible form of NO synthase (iNOS), prostaglandin-E(2) (PGE(2)), and metalloproteinase-9 (MMP-9).

Leukotriene D4-induced activation of smooth-muscle cells from human bronchi is partly Ca2+-independent.

Cysteine-containing leukotrienes (cysteinyl-LTs) are potent bronchoconstrictors and play a key role in asthma. We found that histamine and LTD4 markedly constrict strips of human bronchi (HB) with similar efficacy. However, in human airway smooth-muscle (HASM) cells, LTD4, at variance with histamine, elicited only a small, transient change in intracellular calcium ion concentration.

Effect of endogenous and exogenous prostaglandin E(2) on interleukin-1 beta-induced cyclooxygenase-2 expression in human airway smooth-muscle cells.

We studied the effect of endogenous and exogenous prostaglandin E(2) (PGE(2)), a metabolite of arachidonic acid through the cyclooxygenase (COX) pathway, on interleukin (IL)-1 beta-induced COX-2 expression, using primary cultures of human bronchial smooth-muscle cells (HBSMC). Treatment with exogenous PGE(2) resulted in enhanced expression of IL-1 beta-induced COX-2 protein and messenger RNA (mRNA) as compared with the effect of the cytokine per se. Inhibition of PGE(2) production with a nonselective COX inhibitor (flurbiprofen, 10 microM) resulted in a significant reduction in IL-1 beta- induced COX-2 expression, supporting a role of endogenous COX metabolites in the modulation of COX-2 expression.

Olive oils rich in natural catecholic phenols decrease isoprostane excretion in humans.

This study was undertaken to evaluate, in humans, the antioxidant activity of olive oil phenolics, namely hydroxytyrosol and oleuropein aglycone that share an orthodiphenolic (catecholic) structure. Human volunteers were administered olive oil samples containing increasing amounts of an olive oil phenolic extract that was characterized by gas-chromatography/mass spectrometry. The administration of phenol-rich oils was dose-dependently associated with a decreased urinary excretion of 8-iso-PGF(2alpha), a biomarker of oxidative stress.

Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress.

Background: Oxidative stress is involved in the onset of several degenerative disorders, and epidemiological studies indicate that a high intake of dietary antioxidants, as in the case of the Mediterranean basin, is protective. Olive mill waste waters (OMWWs) are a byproduct of olive oil production rich in phenolic antioxidants, such as hydroxytyrosol. We tested the effects of a low dose of an OMWW extract in a model of sidestream smoke-induced oxidative stress in rats by evaluating the urinary excretion of 8-iso-prostaglandin (PG) F(2alpha) (iPF(2alpha)-III).