Search results for " Type II"
showing 10 items of 542 documents
Diagnostik und Therapie des Morbus Pompe im Kindesalter
2020
Pompe disease is a rare metabolic myopathy caused by deficiency of lysosomal α-glucosidase. Reduced enzyme activity results in abnormal intra- and extralysosomal glycogen deposition as well as impaired cellular function and autophagy. Age at manifestation and severity of disease depend on residual enzyme activity. Enzyme replacement therapy (ERT) is available since 2006. In infantile onset Pompe disease, the most severe form, markedly prolonged survival has resulted in a new phenotype with symptoms and problems not encountered previously. In addition, it became apparent that antibody formation against the recombinant human enzyme may adversely affect the response to ERT. This review summari…
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…
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…
Indicators of Errors for Approximate Solutions of Differential Equations
2014
Error indicators play an important role in mesh-adaptive numerical algorithms, which currently dominate in mathematical and numerical modeling of various models in physics, chemistry, biology, economics, and other sciences. Their goal is to present a comparative measure of errors related to different parts of the computational domain, which could suggest a reasonable way of improving the finite dimensional space used to compute the approximate solution. An “ideal” error indicator must possess several properties: efficiency, computability, and universality. In other words, it must correctly reproduce the distribution of errors, be indeed computable, and be applicable to a wide set of approxi…
Protective effect of apocynin in a mouse model of chemically-induced colitis.
2013
Apocynin, a constituent of Picrorhiza kurroa, successfully inhibits NADPH oxidase and shows promise as an anti-inflammatory drug. Now, we report anti-inflammatory effects of apocynin in an experimental colitis model induced by dextran sulfate sodium as well as the effects on the mediators involved in this process. Apocynin reduced the colitis induced in mice by administration of 5 % dextran sulfate sodium during 7 days. Mice were fed a control diet or a diet supplemented with 2 % of apocynin or 2 % of rutin. Sulfasalazine (50 mg/kg, p. o.) was used as a positive control. Treatment with apocynin and rutin ameliorated the course of colonic inflammation with results similar to those of the ref…