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Potential Therapeutic Effects (potential + therapeutic_effects)
Selected AbstractsIntravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with ,heaves'EQUINE VETERINARY JOURNAL, Issue 6 2006F. C. CAMARGO Summary Reason for performing study: Trimetoquinol (TMQ) is a potent ,-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with ,heaves'. Objectives: To assess the pharmacodynamics of TMQ in horses with ,heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with ,heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001,0.2 ,g/kg bwt i.v. and 0.01,2 ,g/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (,Pplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 ,g/kg bwt) and i.t. (2 ,g/kg bwt) TMQ was evaluated over 6 h. Results: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 ,g/kg bwt, and was still increasing after administration of highest dose, 0.2 ,g/kg bwt. Airway bronchodilation, measured as a decrease in ,Pplmax, also commenced at 0.01 ,g/kg bwt. By the i.t. route, TMQ was 50,100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. Conclusion: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with ,heaves'. Further studies of TMQ by oral and aerosol routes are necessary. Potential relevance: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of ,heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other ,-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of ,heaves'. [source] Molecular Interaction between a Gadolinium,Polyoxometalate and Human Serum AlbuminEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 34 2009Li Zheng Abstract Polyoxometalates (POMs) show promising antibacterial, antiviral (particularly anti-HIV), antitumor, and anticancer activities, but the mechanism of these potential therapeutic effects remains to be elucidated at the molecular level. The interaction between the Gd-containing tungstosilicate [Gd(,2 -SiW11O39)2]13, and human serum albumin (HSA) was studied by several techniques. Fluorescence spectroscopy showed an energy transfer between the single tryptophan residue of HSA and the POM. Circular dichroism led to the conclusion that the POM significantly altered the secondary structure of HSA. Isothermal titration calorimetry revealed an enthalpy-driven binding reaction between HSA and the POM, resulting in the formation of a 1:1 complex.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamideEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Frida Loría Abstract Cannabinoids have recently been approved as a treatment for pain in multiple sclerosis (MS). Increasing evidence from animal studies suggests that this class of compounds could also prove efficient to fight neurodegeneration, demyelination, inflammation and autoimmune processes occurring in this pathology. However, the use of cannabinoids is limited by their psychoactive effects. In this context, potentiation of the endogenous cannabinoid signalling could represent a substitute to the use of exogenously administrated cannabinoid ligands. Here, we studied the expression of different elements of the endocannabinoid system in a chronic model of MS in mice. We first studied the expression of the two cannabinoid receptors, CB1 and CB2, as well as the putative intracellular cannabinoid receptor peroxisome proliferator-activated receptor-,. We observed an upregulation of CB2, correlated to the production of proinflammatory cytokines, at 60 days after the onset of the MS model. At this time, the levels of the endocannabinoid, 2-arachidonoylglycerol, and of the anti-inflammatory anandamide congener, palmithoylethanolamide, were enhanced, without changes in the levels of anandamide. These changes were not due to differences in the expression of the degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase, or of biosynthetic enzymes, diacylglycerol lipase-, and N -acylphosphatidylethanolamine phospholipase-D at this time (60 days). Finally, the exogenous administration of palmitoylethanolamide resulted in a reduction of motor disability in the animals subjected to this model of MS, accompanied by an anti-inflammatory effect. This study overall highlights the potential therapeutic effects of endocannabinoids in MS. [source] Challenges of antiangiogenic cancer therapy: trials and errors, and renewed hopeJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2007Miguel Ángel Medina ,,Introduction ,,What can we learn from the previous failures? ,,Signs of hope ,,Another turn of the screw: a surrogate marker, at last ,,Future avenues for the vascular therapy of cancer Abstract Angiogenesis inhibition has been proposed as a general strategy to fight cancer. However, in spite of the promising preclinical results, a first generation of antiangiogenic compounds yielded poor results in clinical trials. Conceptual errors and mistakes in the design of trials and in the definition of clinical end-points could account for these negative results. In this context of discouraging results, a second generation of antiangiogenic therapies is showing positive results in phases II and III trials at the beginning of the twenty-first century. In fact, several combined treatments with conventional chemotherapy and antiangiogenic compounds have been recently approved. The discovery and pharmacological development of future generations of angiogenesis inhibitors will benefit from further advances in the understanding of the mechanisms involved in human angiogenesis. New styles of trials are necessary, to avoid missing potential therapeutic effects. Different clinical end-points, new surrogate biomarkers and methods of imaging will be helpful in this process. Real efficacy in clinical trials may come with the combined use of antiangiogenic agents with conventional chemotherapy or radiotherapy, and combinations of several antiangiogenic compounds with different mechanisms of action. Finally, the existing antiangiogenic strategies should include other approaches such as vascular targeting or angioprevention. [source] Dynamic contrast-enhanced magnetic resonance imaging as a surrogate marker of tumor response to anti-angiogenic therapy in a xenograft model of glioblastoma multiformeJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2002Axel Gossmann MD Abstract Purpose To evaluate the effects of a neutralizing anti-vascular endothelial growth factor (anti-VEGF) antibody on tumor microvascular permeability, a proposed indicator of angiogenesis, and tumor growth in a rodent malignant glioma model. Materials and Methods A dynamic contrast-enhanced magnetic resonance imaging (MRI) technique, permitting noninvasive in vivo and in situ assessment of potential therapeutic effects, was used to measure tumor microvascular characteristics and volumes. U-87, a cell line derived from a human glioblastoma multiforme, was implanted orthotopically into brains of athymic homozygous nude rats. Results Treatment with the monoclonal antibody A4.6.1, specific for VEGF, significantly inhibited tumor microvascular permeability (6.1 ± 3.6 mL min,1100 cc,1), compared to the control, saline-treated tumors (28.6 ± 8.6 mL min,1100 cc,1), and significantly suppressed tumor growth (P < .05). Conclusion Findings demonstrate that tumor vascular permeability and tumor growth can be inhibited by neutralization of endogenous VEGF and suggest that angiogenesis with the maintenance of endothelial hyperpermeability requires the presence of VEGF within the tissue microenvironment. Changes in tumor vessel permeability and tumor volumes as measured by contrast-enhanced MRI provide an assay that could prove useful for clinical monitoring of anti-angiogenic therapies in brain tumors. J. Magn. Reson. Imaging 2002;15:233,240. © 2002 Wiley-Liss, Inc. [source] Anti-inflammatory, analgesic and anti-oedematous effects of Lafoensia pacari extract and ellagic acidJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2006Alexandre P. Rogerio Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat inflammation. Previously, we demonstrated the anti-inflammatory effect that the ethanolic extract of L. pacari has in Toxocara canis infection (a model of systemic eosinophilia). In this study, we tested the antiinflammatory activity of the same L. pacari extract in mice injected intraperitoneally with ,-glucan present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of acute eosinophilic inflammation). We also determined the anti-oedematous, analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari extract significantly inhibited leucocyte recruitment into the peritoneal cavity induced by ,-glucan. In addition, the L. pacari extract presented significant analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided fractionation of the L. pacari extract in the F1 model led us to identify ellagic acid. As did the extract, ellagic acid presented anti-inflammatory, anti-oedematous and analgesic effects. However, ellagic acid had no anti-pyretic effect, suggesting that other compounds present in the plant stem are responsible for this effect. Nevertheless, our results demonstrate potential therapeutic effects of L. pacari extract and ellagic acid, providing new prospects for the development of drugs to treat pain, oedema and inflammation. [source] Hypochlorite scavenging activity of flavonoidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2004Omidreza Firuzi Scavengers of hypochlorite, a highly reactive oxidant produced by activated phagocytes, could have potential therapeutic effects in diseases in which this oxidant plays a pathogenic role. Flavonoids are polyphenolic substances present in food plants and have been extensively studied for their antioxidant properties against various free radicals. Less is known about their reactivity with hypochlorite. In this study, the hypochlorite scavenging activity of flavonoids was investigated using a microplate assay recently developed in our laboratory. This method evaluates the ability of a substance to inhibit the formation of chloramines in human serum albumin upon oxidation by hypochlorite. Thirteen flavonoids were tested. Most of them inhibited human serum albumin oxidation at micro-molar concentrations and appeared more active than Trolox, a water-soluble equivalent of vitamin E. It was observed that the greater the number of hydroxyl substitutions, the greater the scavenging activity. The 3-hydroxy substitution seemed to be particularly important for scavenging activity, whereas the presence of a 2,3-double bond in the C ring did not. Flavonoids were found to be good hypochlorite scavengers in-vitro and further information is provided about the chemical aspects important for scavenging activity. Thus, flavonoids could have beneficial effects in diseases such as atherosclerosis in which hypochlorite plays a pathogenic role. [source] | ||||||||||