Search results for "Type I"

Role of Nitric Oxide in Gastrointestinal Inflammatory and Ulcerative Diseases: Perspective for Drugs Development

2001

Nitric oxide is a ubiquitous molecule involved in a variety of biological processes. The specific action of NO depends on its enzymatic sources namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) and all three isoforms have been localized in the gastrointestinal tract. Constitutive synthesis of NO by nNOS or eNOS isoforms is involved in the maintaining of the gastrointestinal mucosal integrity through modulation of gastric mucosal blood flow, epithelial secretion and barrier function. However, large amounts of NO synthesized from the inducible isoform have been implicated in tissue injury in the gut during inflammatory reactions. In this review we p…

Immunohistochemical evaluation of matrix molecules associated with wound healing following treatment with an enamel matrix protein derivative in huma…

2003

Application of enamel matrix protein derivative (EMD) onto a debrided and conditioned root surface has been shown to promote periodontal regeneration in animals and humans. However, until now there is virtually no information from humans describing the expression of different matrix molecules in the newly formed periodontal tissues following treatment with EMD. This study investigated immunohistochemically in humans the expression of matrix molecules associated with periodontal tissues reformed after treatment with EMD. Eight patients with intrabony defects were treated with EMD. Six months after surgery teeth together with some of their surrounding soft and hard tissues were removed, fixed…

Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling

2011

Nitric oxide (NO) produced by the endothelium is an important protective molecule in the vasculature. It is generated by the enzyme endothelial NO synthase (eNOS). Similar to all NOS isoforms, functional eNOS transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH), via the flavins flavin adenine dinucleotide and flavin mononucleotide in the carboxy-terminal reductase domain, to the heme in the amino-terminal oxygenase domain. Here, the substrate L-arginine is oxidized to L-citrulline and NO. Cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia or cigarette smoking reduce bioactive NO. These risk factors lead to an enhanced productio…

Normalization of endothelial dysfunction and vascular oxidative stress by chronic atorvastatin treatment in a rat model of streptozotocin-induced dia…

2006

Two-stage adaptive designs with correlated test statistics.

2005

When performing a trial using an adaptive sequential design, it is usually assumed that the data for each stage come from different units; for example, patients. However, sometimes it is not possible to satisfy this condition or to check whether it is satisfied. In these cases, the test statistics and p-values of each stage may be dependent. In this paper we investigate the type I error of two-stage adaptive designs when the test statistics from the stages are assumed to be bivariate normal. Analytical considerations are performed under the restriction that the conditional error function is constant in the continuation region. We show that the decisions can become conservative as well as an…

Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease.

2013

Nitric oxide (NO) produced by the endothelial NO synthase (eNOS) is an antihypertensive, antithrombotic and anti-atherosclerotic molecule. Hypercholesterolemia leads to a reduction in vascular NO bioavailability. This is attributed to a dysfunction of the eNOS enzyme and a reduced eNOS activity. NADPH oxidase-mediated oxidative stress leads to oxidation of tetrahydrobiopterin (BH4), the essential cofactor of eNOS. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting eNOS to a superoxide-producing enzyme. As a consequence of eNOS uncoupling, NO production is reduced and the pre-existing oxidative stress is enhanced, which contribute significantly to atherogenes…

Amphotericin B severely affects expression and activity of the endothelial constitutive nitric oxide synthase involving altered mRNA stability

2000

The therapeutic use of the antifungal drug amphotericin B (AmB) is limited due to severe side effects like glomerular vasoconstriction and risk of renal failure during AmB administration. As nitric oxide (NO) has substantial functions in renal autoregulation, we have determined the effects of AmB on endothelial constitutive NO synthase (ecNOS) expression and activity in human and rat endothelial cell cultures. AmB used at concentrations of 0.6 to 1.25 μg ml−1 led to increases in ecNOS mRNA and protein expression as well as NO production. This was the result of an increased ecNOS mRNA half-life. In contrast, incubation of cells with higher albeit subtoxic concentrations of AmB (2.5–5.0 μg ml…

AVE3085, an enhancer of endothelial nitric oxide synthase, restores endothelial function and reduces blood pressure in spontaneously hypertensive rats

2011

BACKGROUND AND PURPOSE Nitric oxide (NO) plays an important role in endothelial function, and impaired NO production is involved in hypertension. Therefore, compounds that regulate endothelial NO synthase (eNOS) may be of therapeutic benefit. A novel, low molecular weight compound AVE3085 is a recently developed compound with the ability to enhance eNOS transcription. The present study investigated the effects of AVE3085 in endothelial dysfunction associated with hypertension. EXPERIMENTAL APPROACH Spontaneously hypertensive rats (SHRs) were treated with AVE 3085 (10 mg·kg·day−1, orally) for 4 weeks. Isometric force measurement was performed on rings of isolated aortae in organ baths. Prote…

Regulatory evaluation of Glybera in Europe — two committees, one mission

2013

Representing the first gene therapy to be approved in the Western world, alipogene tiparvovec (Glybera; Uniqure) has recently been said to have had a “substantial impact from a regulatory perspective” (Nature Rev. Drug Discov. 11, 664; 2012) 1 . The therapy was granted marketing authorization in the European Union for the treatment of lipoprotein lipase deficiency, which results in a clinically heterogeneous condition with a risk of potentially life-threatening pancreatitis 2 , at the end of 2012. The decision followed a positive opinion by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) 3

A comparison of spreading and motility behaviour of 8701-BC breast carcinoma cells on type I, I-trimer and type V collagen substrata. Evidence for a …

1991

Ductal infiltrating carcinoma (d.i.c.) of human breast is a highly invasive neoplasm characterized by enhanced deposition of collagen. Paradoxically, enhanced collagen deposition is not correlated with inhibition of the migration of tumour cells into the host tissue. d.i.c. is characterized by the reappearance of ‘embryonic’ type I-trimer collagen and an increase in type V collagen content in the matrix. The effects of these two collagen types were compared with type I collagen as culture substrata on the spreading pattern, cytoskeletal organization and motile behaviour of 8701-BC breast carcinoma cells using rhodamine-phalloidin staining, a DNAase I-competition assay, scanning electron mic…