Balance between PGD synthase and PGE synthase is a major determinant of atherosclerotic plaque instability in humans.

Objective: Inducible cyclooxygenase (COX-2) catalyzes the first step in prostanoid biosynthesis and is considered a proinflammatory enzyme. COX-2 and type 1 inducible PGE synthase (mPGES-1) have a role in metalloproteinase (MMP) release leading to plaque rupture. In contrast, lipocalin-type PGD synthase (L-PGDS) has been shown to exert antiinflammatory actions.

Increased soluble CD40 ligand levels in cystic fibrosis.

Chronic inflammation represents a key pathogeneric event in the progression of lung disease in cystic fibrosis (CF). To identify novel mechanisms of the inflammatory reaction in CF and analyze its relation with coagulative activation, we carried-out a cross-sectional study to evaluate circulating levels of the inflammatory mediators soluble (s) CD40L, C-reactive protein (CRP), interleukin (IL)-1beta, the coagulation markers activated factor VII (FVIIa) and prothrombin fragment (F) 1+2, as well as urinary 11-dehydro-thromboxane (TX)B2, an index of in vivo platelet activation, in 34 CF patients and 34 matched healthy subjects. We observed that CF patients displayed significantly increased circulating levels of sCD40L compared to controls [2.

Determinants of F2-isoprostane biosynthesis and inhibition in man.

Several cardiovascular risk factors are characterized by the coexistence of low-grade inflammation, enhanced oxidative stress and lipid peroxidation. It has been hypothesized that F2-isoprostanes, a product of in vivo lipid peroxidation, may transduce the effects of metabolic and hemodynamic abnormalities into increased cardiovascular risk. Thus, the formation of these compounds, including urinary 8-iso-Prostaglandin (PG) F2alpha, has been investigated in clinical settings putatively associated with oxidant stress.

Leptin increase is associated with markers of the hemostatic system in obese healthy women.

Background: Leptin, a hormone secreted by the adipose tissue, might be a link between obesity and increased morbidity for cardiovascular disease. Leptin exerts proinflammatory, pro-angiogenic actions by activating a specific receptor (Ob-Rb) which is expressed in human endothelial cells. Thus, a link may exist between leptin expression and endothelial dysfunction.

Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty.

Background: Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). CD40-CD40L interaction is involved in the pathogenesis of atherosclerosis; however, its role in the pathophysiology of restenosis is still unclear. We tested the hypothesis that soluble CD40L (sCD40L) may be involved in the process of restenosis and that it exerts its effect by triggering a complex group of inflammatory reactions on endothelial and mononuclear cells.

Visual but not spatial working memory deficit in children with spina bifida.

Twenty children with spina bifida and twenty controls were assessed on a battery of visuospatial working memory tests. Children with spina bifida performed as well as the control group in the visuospatial test and in the forward and backward versions of the Corsi test, but were impaired in the 'House Visual Span.' This test, designed in our lab, provides specific information regarding visual ability to discriminate between pictorial targets and lures, and requires specific visual processing of stimuli.

Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women.

Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index > or = 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25).

Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide.

The pharmacological properties of garlic and its derivatives are long known, and their underling mechanisms are being extensively investigated. In this study we have addressed the effects of diallyl disulfide (DADS), an oil-soluble garlic molecule, on cell growth of neuroblastoma cell SH-SY5Y, focusing on the redox events associated with this compound. Treatment of SH-SY5Y cells with DADS resulted in arrest of cell cycle in G(2)/M phase and commitment to apoptosis through the activation of the mitochondrial pathway (Bcl-2 down-regulation, cytochrome c release into the cytosol, and activation of caspase-9 and caspase-3).

The receptor RAGE as a progression factor amplifying arachidonate-dependent inflammatory and proteolytic response in human atherosclerotic plaques: role of glycemic control.

Background: RAGE (receptor for advanced glycation end products [AGEs]) plays a role in diabetic atherosclerosis. Recently, we have demonstrated enhanced expression of cyclooxygenase-2 and PGE synthase-1 (COX-2/mPGES-1) in human symptomatic plaques, and provided evidence that it is associated with metalloproteinase (MMP)-induced plaque rupture. However, the specific transmembrane signaling pathway(s) influencing plaque COX-2/mPGES-1 expression is unknown.

Enhanced lipid peroxidation and platelet activation in the early phase of type 1 diabetes mellitus: role of interleukin-6 and disease duration.

Background: To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A2 biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F2-isoprostane formation in this setting.

Methods And Results: A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM (1 year, group B).

High preprocedural non-HDL cholesterol is associated with enhanced oxidative stress and monocyte activation after coronary angioplasty: possible implications in restenosis.

Objective: To investigate whether enhanced oxidant stress in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher concentration of non-high density lipoprotein (HDL) cholesterol at baseline, and whether this contributes to the inflammatory reaction and luminal renarrowing after PTCA.

Design: An ex vivo and in vitro study of 46 patients who underwent PTCA and who had repeat angiograms after six months. Blood samples were collected immediately before PTCA, and at 24 hours, 48 hours, and 15 days after.

Suppression of the functionally coupled cyclooxygenase-2/prostaglandin E synthase as a basis of simvastatin-dependent plaque stabilization in humans.

Background: The clinical benefits of statins are attributed to changes in plaque composition that lead to reduced metalloproteinase (MMP) activity and plaque stabilization. However, the molecular mechanism of this effect is unclear. Recently, we demonstrated enhanced expression of isoforms of inducible cyclooxygenase (COX) and PGE synthase (COX-2/mPGES) in human symptomatic plaque and provided evidence that this is associated with MMP-induced plaque rupture.

Modulation of aspirin-insensitive eicosanoid biosynthesis by 6-methylprednisolone in unstable angina.

Background: The evidence that inflammation plays a pivotal role in the pathophysiology of acute coronary syndromes prompted us to investigate the effects of glucocorticoid treatment on leukotriene (LT) C4 and thromboxane (TX) A2 biosynthesis in unstable angina.

Methods And Results: Urinary LTE4 and 11-dehydro-TXB2 were significantly higher in 12 patients with unstable angina than in 12 patients with stable angina and 12 patients with nonischemic chest pain. Furthermore, we randomized the unstable angina patients to receive intravenous 6-methylprednisolone (6-MP; 1 mg/kg BID for 2 days) or matching placebo and collected 12 consecutive 6-hour urine samples before and during the infusions.

Cerec 3 for orthodontics: a tool for treating deep bite.

Bite-opening procedures are used in the early stages of orthodontic fixed treatment in order to: ease antero-posterior tooth movements; bracket the mandibular arch and level the Curve of Spee; prevent mandibular brackets from debonding; use regular straight archwires to proceed with treatment. For these purposes, removable or bonded biteplanes are universally recognized as very effective when the bite-opening is needed. Conventional orthodontic procedures include clinical solutions which effectively open the bite, but they all lack sufficient hygiene, comfort, and esthetics.

Association between enhanced soluble CD40L and prothrombotic state in hypercholesterolemia: effects of statin therapy.

Background: Hypercholesterolemia is associated with inflammation and the prothrombotic state. CD40-CD40 ligand (CD40L) interactions promote a prothrombotic response in nucleated cells. The aim of this study was to characterize the in vivo expression of soluble CD40L (sCD40L) in hypercholesterolemia, to correlate it with the extent of the prothrombotic state, and to investigate whether it may be modified by statins.

How to improve digital dental radiograph reproducibility: an individualized technique.

Today, the advantages of the use of digital dental radiography as a valid alternative to conventional techniques are well known. In clinical dental practice, it can be useful to realize intraoral dental x-rays that can be compared, even after some years. The use of a conventional XCP instrument with the "long cone" technique helps to limit image distortion, but the comparison is poor.

Oxidative stress and platelet activation in homozygous homocystinuria.

Background: Severe hyperhomocysteinemia due to cystathionine beta-synthase deficiency (CbetaSD) is associated with early atherothrombotic vascular disease. Homocysteine may exert its effects by promoting oxidative damage. In the present study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG) F(2alpha), a platelet-active product of arachidonic acid peroxidation, is enhanced in CbetaSD and whether it correlates with in vivo platelet activation, as reflected by thromboxane (TX) metabolite excretion.

Elevated circulating levels of monocyte chemoattractant protein-1 in patients with restenosis after coronary angioplasty.

Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes; however, its role in the pathophysiology of restenosis is still unclear. We set out to investigate the role of MCP-1 in restenosis after PTCA.

Role of the electrostatic loop of Cu,Zn superoxide dismutase in the copper uptake process.

Cu,Zn superoxide dismutases are characterized by the presence of four highly conserved charged residues (Lys120, Glu/Asp130, Glu131 and Lys134), which are placed at the edge of the active site channel and have been shown to be individually involved in the electrostatic attraction of the substrate toward the catalytically active copper ion. By genetic engineering we mutated these four residues into neutrally charged ones (Leu120, Gln130, Gln131, Thr134). The effects of these mutations on the rate of superoxide dismutation were not dramatic.

Aspirin: new cardiovascular uses for an old drug.

Inhibition of TXA2-dependent platelet function by aspirin may lead to prevention of thrombosis as well as to excess bleeding. The balance between the two depends critically on the absolute thrombotic versus hemorrhagic risk of the patient. As the risk of experiencing a major vascular event increases, so does the absolute benefit of antiplatelet prophylaxis with aspirin [Figure-see text].

Oxidative stress and cardiovascular complications in diabetes: isoprostanes as new markers on an old paradigm.

Long-term vascular complications still represent the main cause of morbidity and mortality in diabetic patients. Although randomized long-term clinical studies comparing the effects of conventional and intensive therapy have demonstrated a clear link between hyperglycemia and the development of complications of diabetes, they have not defined the mechanism through which excess glucose results in tissue damage. Evidence has accumulated indicating that oxidative stress may play a key role in the etiology of diabetic complications.

Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina.

Background: Unstable angina is associated with enhanced lipid peroxidation and reduced antioxidant defenses. We have previously reported aspirin failure in the suppression of enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation in this setting. We tested the hypothesis that the in vivo formation of the F(2)-isoprostane 8-iso-prostaglandin (PG)F(2alpha), a bioactive product of arachidonic acid peroxidation, is enhanced in unstable angina and contributes to aspirin-insensitive TX biosynthesis.

Effects of vitamin E supplementation on F(2)-isoprostane and thromboxane biosynthesis in healthy cigarette smokers.

Background: Increased formation of 8-iso-prostaglandin (PG) F(2alpha) and thromboxane (TX) A(2), potent agonists of platelet and vascular thromboxane (TH)/PGH(2) receptors, has been detected in cigarette smokers. We performed a randomized, double-blind, placebo-controlled study of the effects of vitamin E (300, 600, and 1200 mg/d, each dose for 3 consecutive weeks) on 8-iso-PGF(2alpha) and TXA(2) biosynthesis in 46 moderate cigarette smokers.

Methods And Results: Urinary immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2), plasma vitamin E, and serum TXB(2) were measured by previously validated techniques.

Cu,Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells.

Nitric oxide (NO) challenge to human neuroblastoma cells (SH-SY5Y) ultimately results in apoptosis. Tumor suppressor protein p53 and cell cycle inhibitor p21 accumulate as an early sign of S-nitrosoglutathione-mediated toxicity. Cytochrome c release from mitochondria and caspase 3 activation also occurred.