Chronic Elevation (chronic + elevation)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Review article: drug-induced liver injury in clinical practice

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010
E. Björnsson
Aliment Pharmacol Ther 2010; 32: 3,13 Summary Background, Drug-induced liver injury (DILI) is an important differential diagnosis in many patients in clinical hepatology. DILI is the leading cause of acute liver failure and is an important safety issue when new drugs are developed. Aims, To provide a review of the recent data on DILI with particular focus on the most common and relevant issues seen in clinical practice. Methods, A Medline search was undertaken to identify relevant literature using search terms including ,drug-induced liver injury' and ,hepatotoxicity'. Results, The true incidence of DILI remains unknown but incidence up to 14 cases per 100 000 inhabitants and year has been reported. Antibiotics, analgesics and NSAIDs are the most common drugs causing liver injury. Idiosyncratic DILI has been shown to have a dose-dependent component and drugs without significant hepatic metabolism rarely cause DILI. Chronic elevation in liver enzymes can develop after DILI but this is rarely associated with clinical morbidity or mortality. Conclusions, Drug-induced liver injury remains a diagnostic challenge. Multicentre studies and international collaborative work with well-characterized patients will increase our understanding of liver injury associated with drugs. New therapies for acute liver failure resulting from drugs are needed. [source]

Free fatty acids as mediators of adaptive compensatory responses to insulin resistance in dexamethasone-treated rats

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008
Michela Novelli
Abstract Background Chronic low-dose dexamethasone (DEX) treatment in rats is associated to insulin resistance with compensatory hyperinsulinaemia and reduction in food intake. We tested the hypothesis that the elevation in circulating free fatty acids (FFAs) induced by DEX is the common mediator of both insulin resistance and insulin hyperproduction. Methods For this purpose, an anti-lipolytic agent was administered during DEX treatment to lower lipacidaemia for several hours prior to glucose and insulin tolerance tests. Leptin expression in adipose tissue (by Northern blot) and plasma leptin levels (by radioimmunoassay) were also investigated to verify whether a rise in circulating leptin could be responsible for the anorectic effect of DEX. Results Our data show that a transient pharmacological reduction of elevated plasma FFA levels abates the post-loading hyperinsulinaemia and counteracts the insulin resistance induced by DEX, supporting the hypothesis that the chronic elevation in FFAs is the common mediator of DEX-induced changes. Despite enhanced leptin expression in white adipose tissue, DEX-treated rats show no significant increase in plasma leptin levels. This suggests that the anorectic effect of DEX should be mediated, at least partially, by other factors, possibly related to the influence of concomitantly elevated plasma FFA and insulin levels on the hypothalamic centers regulating feeding. Conclusions Our results sustain the idea that a prolonged increase in plasma FFA levels plays an important role in the adaptive regulation of glucose and energy homeostasis, not only by potentiating insulin secretion but also by providing a signal of ,nutrient abundance' capable of restraining food intake. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Interferon-alpha regulates the dynamic balance between human activated regulatory and effector T cells: implications for antiviral and autoimmune responses

IMMUNOLOGY, Issue 1 2010
Amit Golding
Summary An adequate effector response against pathogens and its subsequent inactivation after pathogen clearance are critical for the maintenance of immune homeostasis. This process involves an initial phase of T-cell effector (Teff) activation followed by the expansion of regulatory T cells (Tregs), a unique cell population that limits Teff functions. However, significant questions remain unanswered about the mechanisms that regulate the balance between these cell populations. Using an in vitro system to mimic T-cell activation in human peripheral blood mononuclear cells (PBMC), we analysed the patterns of Treg and Teff activation, with special attention to the role of type I interferon (IFN-I). Interestingly, we found that IFN-,, either exogenously added or endogenously induced, suppressed the generation of CD4+ FoxP3HI IFN-,Neg activated Tregs (aTregs) while simultaneously promoting propagation of CD4+ FoxP3Low/Neg IFN-,Pos activated Teffs (aTeffs). We also showed that IFN-,-mediated inhibition of interleukin (IL)-2 production may play an essential role in IFN-,-induced suppression of aTregs. In order to test our findings in a disease state with chronically elevated IFN-,, we investigated systemic lupus erythematosus (SLE). Plasma from patients with SLE was found to contain IFN-I activity that suppressed aTreg generation. Furthermore, anti-CD3 activated SLE PBMCs exhibited preferential expansion of aTeffs with a very limited increase in aTreg numbers. Together, these observations support a model whereby a transient production of IFN-, (such as is seen in an early antiviral response) may promote CD4 effector functions by delaying aTreg generation, but a chronic elevation of IFN-, may tip the aTeff:aTreg balance towards aTeffs and autoimmunity. [source]

Experimental glaucoma development in albine rabbits

ACTA OPHTHALMOLOGICA, Issue 2007
N GUERRI
Purpose: To compare four different glaucoma development models in albine rabbits, based on achieving a chronic elevation of intraocular pressure (IOP). Methods: A total of 16 animals were used for the glaucoma development model. Rabbits were divided in four groups: Cautery of three vortex veins was performed in the first group (four animals) and cautery of four vortex veins in the second group (four animals). Three vortex veins were ligated in the third group (four animals) and ligation of four vortex veins was performed in the last group (four animals). IOP was measured by Tonovet rebound tonometer during six weeks follow up. The opposite unoperated eye served as control. Results: Cauterization of four vortex veins (second group) and ligation of four vortex veins (fourth group) achieved IOP elevation (40mmHg) but only for the first twenty four hours. The others groups IOP did not reach statistical differences between treated and control eye. None of the methods developed chronic elevation of IOP. Conclusions: Vortex vein surgery in albine rabbits was not able to achieve chronic elevation of IOP. Therefore, none of this methods showed capacity to develop a glaucoma experimental model. [source]