Search results for "Ley"
showing 10 items of 1218 documents
Synthesis and pharmacological study of ethyl 1-methyl-5-(substituted 3,4-dihydro-4-oxoquinazolin-3-yl)-1H-pyrazole-4-acetates
2001
Several new ethyl 1-methyl-5-(substituted 3,4-dihydro-4-oxoquinazolin-3-yl)-1H-pyrazole-4-acetates 2, substituted at 2 and, alternatively at, 6, 7 or 8 positions of the quinazolinone nucleus, were synthesised. The compounds were screened for their analgesic and antiinflammatory activities, acute toxicity and ulcerogenic effect. Substitution in the benzene moiety of the quinazolinone ring did not show any advantage for the analgesic activity, whereas it improved in some cases the antiinflammatory activity. Some compounds showed appreciable antiinflammatory activity and, at the same time, very low ulcerogenic index.
1-imidazolyl(alkyl)-substituted di- and tetrahydroquinolines and analogues: syntheses and evaluation of dual inhibitors of thromboxane A(2) synthase …
2000
A series of 1-imidazolyl(alkyl)-substituted quinoline, isoquinoline, naphthalene, benzo[b]furan, and benzo[b]thiophene derivatives was synthesized as dual inhibitors of thromboxane A(2) synthase (P450 TxA(2)) and aromatase (P450 arom). Dual inhibition of these enzymes could be a novel strategy for the treatment of mammary tumors and the prophylaxis of metastases. The most potent dual inhibitors, 5-(2-imidazol-1-ylethyl)-7,8-dihydroquinoline (31) (P450 TxA(2): IC(50) = 0.29 microM; P450 arom: IC(50) = 0.50 microM) and its 5, 6-saturated analogue 30 (P450 TxA(2): IC(50) = 0.68 microM; P450 arom: IC(50) = 0.38 microM), showed a stronger inhibition of both target enzymes than the reference comp…
Adhesive interaction measured between AFM probe and lung epithelial type II cells
2007
The toxicity of inhaled nanoparticles entering the body through the lung is thought to be initially defined by the electrostatic and adhesive interaction of the particles with lung's wall. Here, we investigated the first step of the interaction of nanoparticles with lung epithelial cells using atomic force microscope (AFM) as a force apparatus. Nanoparticles were modeled by the apex of the AFM tip and the forces of interaction between the tip and the cell analyzed over time. The adhesive force and work of adhesion strongly increased for the first 100 s of contact and then leveled out. During this time, the tip was penetrating deeply into the cell. It first crossed a stiff region of the cell…
Acute cardio-respiratory effects in rats of PS4α, an antineoplastic peptidoglycan from Mycobacterium vaccae
2001
Abstract PS4α is a high molecular weight peptidoglycan extracted from Mycobacterium vaccae, which has demonstrated considerable antineoplastic activity in-vivo without apparent toxicity. Available for testing in only small quantities, a sensitive in-vivo method for measuring pulse and breathing rates in cannulated rats was applied to this compound at doses of 5, 50 and 500 μg kg−1. Various parameters (mean arterial pressure, maximum transpulmonary pressure, compliance, heart rate, minute volume, respiratory rate and tidal volume) were followed for up to 1 h and demonstrated no significant deviation in the baseline values obtained before injection. This compound at doses up to 500 μg kg−1 ha…
Small volume resuscitation with tempol is detrimental during uncontrolled hemorrhagic shock in rats.
2005
In a previous study, titration of a hypertonic saline (HTS) solution during severe uncontrolled hemorrhagic shock (UHS) failed to reduce mortality. In a separate study, a novel antioxidant, polynitroxylated albumin (PNA) plus tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), infused during shock increased long-term survival. We hypothesized that combining potent antioxidants with a hypertonic solution during UHS would preserve the logistical advantage of small volume resuscitation and improve survival.An UHS outcome model in rats was used. UHS phase I (90 min) included blood withdrawal of 30 ml/kg over 15 min, followed by tail amputation for uncontrolled bleeding. At 20 min, rats wer…
Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats.
2002
In volume- or pressure-controlled hemorrhagic shock (HS) a bolus intravenous infusion of hypertonic/hyperoncotic solution (HHS) proved beneficial compared to isotonic crystalloid solutions. During uncontrolled HS in animals, however, HHS by bolus increased blood pressure unpredictably, and increased blood loss and mortality. We hypothesized that a titrated i.v. infusion of HHS, compared to titrated lactated Ringer's solution (LR), for hypotensive fluid resuscitation during uncontrolled HS reduces fluid requirement, does not increase blood loss, and improves survival.We used our three-phased uncontrolled HS outcome model in rats. HS phase I began with blood withdrawal of 3 ml/100g over 15 mi…
Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain
2012
Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood–brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3–12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesized that chemotherapy disrupts learning via decreases in hippocampal adult…
Brain met-enkephalin immunostaining after subacute and subchronic exposure to benzene
1994
Benzene is used in a wide variety of domestic and occupational activities, and due to its lipophilic nature, it accumulates in lipid-rich tissues like the brain. In this sense, neurotoxic action has long been associated with organic solvent exposure and it has been shown that benzene, injected in a single dose or during a prolongued administration, modifies the content of dopamine, noradrenaline, serotonin and its main metabolite 5-hydroxy indolacetic acid, in several brain regions of the rat, then revealing a stimulating action on brain monoamine synthesis and turnover. However, information concerning neurotoxic action of benzene exposure in vivo on peptidergic neuromodulatory systems is s…
Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human
2004
Abstract 4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive designer drug of abuse that is sold under the street names “Venus”, “Bromo”, “Erox”, “XTC” or “Nexus”. Concern has been raised because only little is known about its toxicity and metabolism in humans. In the present study we incubated 2C-B with human, monkey, dog, rabbit, rat and mouse hepatocytes to identify the metabolites formed and to determine possible toxic effects as evidenced by an ATP assay. Our data allow construction of the main metabolic pathways of 2C-B. Oxidative deamination results in the 2-(4-bromo-2,5-dimethoxyphenyl)-ethanol (BDMPE) and 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) metabolites. Additio…
Comparison of the metabolism of 7-ethoxycoumarin and coumarin in precision-cut rat liver and lung slices
1995
The metabolism of 7-ethoxycoumarin and [3-(14)C]coumarin was compared in precision-cut rat liver and lung slices. The lung slices were prepared using an agarose gel instilling technique enabling the production of tissue cylinders followed by lung slices employing a Krumdieck tissue slicer. Both 50 microM 7-ethoxycoumarin and 50 microM [3-(14)C]coumarin were metabolized by rat liver and lung slices. 7-Ethoxycoumarin was converted to 7-hydroxycoumarin (7-HC) which was conjugated with both D-glucuronic acid and sulfate. 7-HC sulfate was the major metabolite formed by both liver and lung slices. [3-(14)C]Coumarin was metabolized by rat liver and lung slices to both polar products and to metabol…