Search results for "Propionate"
showing 10 items of 144 documents
Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients
2016
Background: Inhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD patients were used to compare the anti-inflammatory effects of aclidinium bromide (a long-acting muscarinic antagonist) with corticosteroids and their potential additive effect. Methods: Human sputum and blood neutrophils were isolated from healthy individuals ( n = 37), patients with stable COPD ( n = 52) and th…
Using NMR in saliva to identify possible biomarkers of glioblastoma and chronic periodontitis
2018
Nowadays there is increasing interest in identifying-and using-metabolites that can be employed as biomarkers for diagnosing, treating and monitoring diseases. Saliva and NMR have been widely used for this purpose as they are fast and inexpensive methods. This case-control study aimed to find biomarkers that could be related to glioblastoma (GBL) and periodontal disease (PD) and studied a possible association between GBL and periodontal status. The participants numbered 130, of whom 10 were diagnosed with GBL and were assigned to the cases group, while the remaining 120 did not present any pathology and were assigned to the control group. On one hand, significantly increased (p < 0.05) meta…
A human relevance investigation of PPARα-mediated key events in the hepatocarcinogenic mode of action of propaquizafop in rats
2018
Propaquizafop is an herbicide with demonstrated hepatocarcinogenic activity in rodents. A rodent-specific mode of action (MOA) in the liver via activation of peroxisome proliferator-activated receptor α (PPARα) has been postulated based on existing data. Experience with PPARα-inducing pharmaceuticals indicates a lack of human relevance of this MOA. The objective of the present investigation was to evaluate the dependency of early key events leading to liver tumors on PPARα activation in wildtype (WT) compared to PPARα-knockout (KO) rats following 2 weeks exposure to 75, 500 and 1000 ppm propaquizafop in the diet. In WT rats, both WY-14643 (50 mg/kg bw/day) and propaquizafop (dose-dependentl…
Functional evidence of multidrug resistance transporters (MDR) in rodent olfactory epithelium.
2012
WOS: 000305340700029; International audience; BACKGROUND: P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated. PRINCIPAL FINDINGS: Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM) accumulation assay on acute rat and mouse olfactory tissue slices.…
GAS CHROMATOGRAPHIC ESTIMATION OF ACETYLCHOLINE IN THE RABBIT HEART USING A NITROGEN SELECTIVE DETECTOR
1973
The distribution of ACh in the rabbit heart was investigated by a modified gas chromatographic estimation method. ACh was extracted with perchloric acid, precipitated as reineckate and demethylated with sodium benzenethiolate. The tertiary amines derived from ACh and other choline esters were concentrated by a microdistillation procedure. Gas chromatography was performed using a nitrogen selective detector. In the range of concentrations between 0.4 and 2.5 nmol ACh per tissue sample the coefficient of variation was 5.2 per cent. The recovery of ACh added to heart extracts was 101 per cent. Evidence for the identity of the choline ester isolated from rabbit hearts and authentic ACh was obta…
Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: possible link to the antiischemic activities of mildro…
2004
Mildronate [3-(2,2,2-trimethylhydrazine) propionate (THP)] is an antiischemic drug acting mainly via inhibition of fatty acid beta-oxidation. Some effects of the drug cannot be explained by the latter mechanism. We tested the eventual nitric oxide (NO) dependence of the mildronate action. Mildronate, gamma-butyrobetaine (GBB) and GBB methyl ester induced transient increases in nitric oxide (NO) concentrations in rat blood and myocardium. In vitro, these compounds neither modified the activities of purified neuronal and endothelial recombinant nitric oxide synthases (NOSs) nor were able to interact with their active site. GBB induced vasodilatation at high concentrations only (EC50 = 5 x 10(…
Clinical and Biological Heterogeneity in Children with Moderate Asthma
2003
To evaluate the relationship between inflammatory markers and severity of asthma in children, the amount of interleukin-8 (IL-8) and granulocyte/macrophage colony-stimulating factor (GM-CSF) released by peripheral blood mononuclear cells, exhaled nitric oxide (FE NO) levels, p65 nuclear factor-kappaB subunit, and phosphorylated IkBalpha expression by peripheral blood mononuclear cells were assessed in six control subjects, 12 steroid-naives subjects with intermittent asthma, and 17 children with moderate asthma. To investigate their predictive value, biomarker levels were correlated with the number of exacerbations during a 18-month follow-up period. We found that GM-CSF release was higher …
Tolerance-Inducing Dose of 3-Nitropropionic Acid Modulates bcl-2 and bax Balance in the Rat Brain: A Potential Mechanism of Chemical Preconditioning
2000
Many studies have reported ischemia protection using various preconditioning techniques, including single dose 3-nitropropionic acid (3-NPA), a mitochondrial toxin. However, the cellular signal transduction cascades resulting in ischemic tolerance and the mechanisms involved in neuronal survival in the tolerant state still remain unclear. The current study investigated the mRNA and protein expression of the antiapoptotic bcl-2 and the proapoptotic bax, two antagonistic members of the bcl-2 gene family, in response to a single dose of 3-NPA, to global cerebral ischemia–reperfusion, and to the combination of both 3-NPA-pretreatment and subsequent global cerebral ischemia–reperfusion. Brain h…
Increased Hypoxic Tolerance by Chemical Inhibition of Oxidative Phosphorylation: “Chemical Preconditioning”
1997
A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: “chemical preconditioning.” The amplitude of CA1population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 ± 27% (mean ± SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1–24 h prior to slice preparation (preconditioned slices), psap improved to 90 ± 15% (p < 0.01). Posthypoxic oxygen free radical…
Pre-clinical assessment of a water-in-fluorocarbon emulsion for the treatment of pulmonary vascular diseases
2019
Abstract Hypoxic pulmonary vasoconstriction (HPV) is a well-characterized vascular response to low oxygen pressures and is involved in life-threatening conditions such as high-altitude pulmonary edema (HAPE) and pulmonary arterial hypertension (PAH). While the efficacy of oral therapies can be affected by drug metabolism, or dose-limiting systemic toxicity, inhaled treatment via pressured metered dose inhalers (pMDI) may be an effective, nontoxic, practical alternative. We hypothesized that a stable water-in-perfluorooctyl bromide (PFOB) emulsion that provides solubility in common pMDI propellants, engineered for intrapulmonary delivery of pulmonary vasodilators, reverses HPV during acute h…