Search results for "Drug tolerance"
showing 10 items of 44 documents
Evidence for a relationship between mitochondrial Complex I activity and mitochondrial aldehyde dehydrogenase during nitroglycerin tolerance: effects…
2012
The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GIN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GIN tolerance (in rat and human vessels) produced a decrease in mitochondrial 02 consumption. Co-incubation with the mitochondria-targeted antioxidant mitoquinone (MQ 10(-6) mol/L) or with glutathione ester (GEE, 10(-4) mol/L) blocked GTN tolerance and the effects of GTN on mitochondrial respiration and aldehyde dehydrogenase 2 (ALDH-2) activity. Biotransformation of GTN depended on the mitochondria being functionally active, particularly mitochondrial Comp…
Mitochondrial oxidative stress and nitrate tolerance – comparison of nitroglycerin and pentaerithrityl tetranitrate in Mn-SOD+/- mice
2006
Abstract Background Chronic therapy with nitroglycerin (GTN) results in a rapid development of nitrate tolerance which is associated with an increased production of reactive oxygen species (ROS). According to recent studies, mitochondrial ROS formation and oxidative inactivation of the organic nitrate bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) play an important role for the development of nitrate and cross-tolerance. Methods Tolerance was induced by infusion of wild type (WT) and heterozygous manganese superoxide dismutase mice (Mn-SOD+/-) with ethanolic solution of GTN (12.5 μg/min/kg for 4 d). For comparison, the tolerance-free pentaerithrityl tetranitrate (PETN, 1…
Randomized Comparative Trial with Ceftizoxime and Cefotaxime in Urinary Tract Infections
1984
Ceftizoxime, a new, semisynthetic, beta-lactamase-resistant cephalosporin, is not metabolized in man and is excreted almost entirely as the original active compound in the urine. The efficacy and safety of ceftizoxime were assessed in 80 patients with acute and chronic urinary infections, with and without associated pathological conditions, in comparison with cefotaxime. Two dosage schedules, 1 g or 0.5 g every 12 h, i.v. or i.m. for 10 days, were adopted according to the severity of each case and to separate randomization tables for each schedule; causal agents were all sensitive to both drugs in vitro. The overall results were excellent. Safety was excellent in almost all cases. In this t…
Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients
2009
AIM: To investigate the efficacy and safety of cape-citabine plus irinotecan ± bevacizumab in advanced or metastatic colorectal cancer patients. METHODS: Forty six patients with previously untreated, locally-advanced or metastatic colorectal cancer (mCRC) were recruited between 2001-2006 in a prospective open-label phase II trial, in German community-based outpatient clinics. Patients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of > grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were respon…
Pegylated interferon therapy in chronic hepatitis C: lights and shadows of an innovative treatment
2007
Abstract Pegylated interferon (PEG-IFN) in combination with ribavirin is the standard of treatment for chronic hepatitis C. Several viral and host factors influence the outcome of treatment, such as hepatitis C virus (HCV) genotype, baseline viral load, viral kinetics, race, body weight, advanced liver disease, HIV co-infection, and adherence to therapy. Monitoring the response of HCV to treatment during the early time points (4 weeks or 12 weeks) after initiation of therapy has emerged as a critical tool to predict sustained virologic response (SVR), defined as undetectable serum HCV RNA 24 weeks after the end of therapy. To counterbalance the influence of host and viral factors, treatment…
Explaining the phenomenon of nitrate tolerance.
2005
During the last century, nitroglycerin has been the most commonly used antiischemic and antianginal agent. Unfortunately, after continuous application, its therapeutic efficacy rapidly vanishes. Neurohormonal activation of vasoconstrictor signals and intravascular volume expansion constitute early counter-regulatory responses (pseudotolerance), whereas long-term treatment induces intrinsic vascular changes, eg, a loss of nitrovasodilator-responsiveness (vascular tolerance). This is caused by increased vascular superoxide production and a supersensitivity to vasoconstrictors secondary to a tonic activation of protein kinase C. NADPH oxidase(s) and uncoupled endothelial nitric oxide synthase …
Pre-treatment with high doses of cocaine decreases the reinforcing effects of cocaine in the conditioned place preference paradigm.
2012
The aim of the present study was to determine if pre-exposure to high doses of cocaine can subsequently alter the rewarding effects of this drug. Adult male mice received a pretreatment of physiological saline, or 12.5 or 25 mg/kg of cocaine (one injection a day for five days). After an interval of six days without injections, the rewarding effects of low doses of cocaine (0.5, 1 or 1.5 mg/kg) were evaluated in the conditioned place preference (CPP) paradigm. Doses of 1 and 1.5 mg/kg induced a clear CPP in animals pre-treated with saline but were ineffective in those pre-treated with 25 mg/kg of cocaine. Only the dose of 1.5 mg/kg induced CPP in mice pre-treated with 12.5 mg/kg of cocaine. …
Opioid Poorly-Responsive Cancer Pain. Part 2
2001
Basic research in experimental pain models may illuminate the phenomenon of cancer pain that is poorly responsive to opioid drugs. Research findings can be valuable in formulating new strategies in clinical practice. This review evaluated experimental observations in terms of the events that occur in cancer patients receiving opioid therapy for pain.
The Life Cycle of the Mu-Opioid Receptor
2020
Opioid receptors (ORs) are undisputed targets for the treatment of pain. Unfortunately, targeting these receptors therapeutically poses significant challenges including addiction, dependence, tolerance, and the appearance of side effects, such as respiratory depression and constipation. Moreover, misuse of prescription and illicit narcotics has resulted in the current opioid crisis. The mu-opioid receptor (MOR) is the cellular mediator of the effects of most commonly used opioids, and is a prototypical G protein-coupled receptor (GPCR) where new pharmacological, signalling and cell biology concepts have been coined. This review summarises the knowledge of the life cycle of this therapeutic …
The impact of coffee on health
2013
Abstract Objective Coffee is a beverage used worldwide. It includes a wide array of components that can have potential implication on health. We have reviewed publications on the impact of coffee on a series of health outcomes. Methods Articles published between January 1990 and December 2012 were selected after crossing coffee or caffeine with a list of keywords representative of the most relevant health areas potentially affected by coffee intake. Results Caffeine, chlorogenic acids and diterpenes are important components of coffee. Tolerance often acts as a modulator of the biological actions of coffee. There is a significant impact of coffee on the cardiovascular system, and on the meta…