Search results for " TOXICOLOGY AND PHARMACEUTICS"
showing 10 items of 461 documents
Interspecies differences in cancer susceptibility and toxicity.
1999
One of the most complex challenges to the toxicologist represents extrapolation from laboratory animals to humans. In this article, we review interspecies differences in metabolism and toxicity of heterocyclic amines, aflatoxin B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and related compounds, endocrine disrupters, polycyclic aromatic hydrocarbons, tamoxifen, and digitoxin. As far as possible, extrapolations to human toxicity and carcinogenicity are performed. Humans may be more susceptible to the carcinogenic effect of heterocyclic amines than monkeys, rats, and mice. Especially, individuals with high CYP1A2 and 3A4 activities and the rapid acetylator phenotype may be expected to have …
Age differences in the role of the cannabinoid type 1 receptor on glutamatergic neurons in habituation and spatial memory acquisition
2015
Abstract Aims Aging is typically linked with a decline in memory performance and alterations in neural integrity. In pathological aging such as Alzheimer's disease, these effects are aggravated. Studies using cannabinoid CB1 receptor-deficient mice have shown a role of the endocannabinoid system in memory processing and neuroprotection. As the CB1 receptor is expressed in various neuronal populations, in this study, we aimed at investigating the consequences of CB1 receptor gene inactivation in cortical glutamatergic neurons in mice (Glu-CB1-KO) in regard to age-related alterations in spatial memory performance. Main methods Juvenile (5.5–7.5 weeks), adult (5.5–7 months), and old (11.5–14 m…
Studies on the reliability of a bihyperbolic functional absorption model. II. Phenylalkylamines
1987
Evidence is given that demonstrates the reliability of the bihyperbolic equation, proposed by Pla-Delfina and Moreno, in fitting the correlation between absorption rate constants (ka) found in the small intestine and in the colon of the living anesthetized rat, and partition constants (1/R.F−1), for a series of phenylalkylamines, a group of compounds which differ largely from others which have been tested. Emphasis is laid on the nonexistence of an optimum of lipophilicity for intestinal absorption/partition correlation: This feature makes inapplicable the probabilistic approaches to the reported data.
Weekly 5-fluorouracil and folinic acid plus escalating doses of cisplatin with glutathione protection in patients with advanced head and neck cancer.
1992
Twenty-two patients with advanced head and neck carcinoma were treated with 5FU 400 mg-2 m-1 week and folinic acid 500 mg m-2 week-1 plus CDDP in escalating doses from 20 to 40 mg m-2 week-1 without forced diuresis. Reduced gluthatione at the dose of 1.5 g m-2 was employed to protect patients from CDDP-related nephrotoxicity. The aims of the study were: a) to evaluate the therapeutic efficacy of this schedule, and b) to evaluate reduced gluthatione as uroprotector. Out of 20 evaluable patients 14 (70 %) had a major objective response. A CR with a mean duration of 9.0+ months was achieved in 15 % of the patients, a PR of 5.8+ months in 55 % of the patients, while 3 patients had stable diseas…
Fluorescent benzofurazan-cholic acid conjugates for in vitro assessment of bile acid uptake and its modulation by drugs.
2009
One of the most common mechanisms of hepatotoxicity is drug-induced cholestasis. Hence, new approaches for screening the cholestatic potential of drug candidates are desirable. In this context, we describe herein the use of synthetic 4-nitrobenzo-2-oxa-1,3-diazole (NBD) fluorescent conjugates of cholic acid (ChA) at positions 3alpha, 3beta, 7alpha, and 7beta for in vitro assessment of bile acid uptake. All the conjugates show a strong absorption band between 400 and 550 nm and have a fluorescence quantum yield of approximately 0.45, with an emission maximum centered at approximately 530 nm. After their photophysical characterization, 3alpha-, 3beta-, 7alpha-, and 7beta-NBD-ChA were used to …
Effect of serum protein binding on pharmacokinetics and anticoagulant activity of phenprocoumon in rats.
1980
The relationship among serum protein binding, kinetics of elimination, distribution, and anticoagulant activity of phenprocoumon was investigated in 25 selected outbred Sprague-Dawley rats which differed in the extent of serum protein binding of this drug. In addition, the serum protein binding of phenprocoumon was altered in inbred Lewis rats by continuous treatment with tolbutamide. This drug was found to displace phenprocoumon from serum proteins without affecting its intrinsic clearance. The serum free fraction values (fs)of the selected Sprague-Dawley rats ranged from 0.0053 to 0.0145. There were positive and linear correlations between fsand the first-order elimination rate constant (…
In vivo and in vitro antioxidant properties of furosemide
2003
The aim of this study was to investigate in vivo and in vitro antioxidant properties of furosemide. In vitro, human red blood cells were submitted to oxidative stress (AAPH), in absence or in presence of different concentrations of furosemide. Potassium efflux was measured in order to quantify the oxidative stress after the action of AAPH on red blood cells. Allophycocyanin assay was also used to investigate antioxidant capacities of furosemide. For the in vivo experiment, male Wistar rats were used. A control group (n = 5) was treated by a daily intraperitoneal injection of saline solution (0.2 ml); 2 other groups (J0 and J+) were treated for 7 days by one daily intraperitoneal injection o…
Ex vivo and in vivo evaluation of [18F]PR04.MZ in rodents: a selective dopamine transporter imaging agent.
2009
N-4-Fluorobut-2-yn-1-yl-2beta-carbomethoxy-3beta-phenyltropane (PR04.MZ) has been developed as dopamine transporter (DAT) ligand for molecular imaging. It contains a terminally fluorinated, conformationally constrained nitrogen substituent that is well suited for the introduction of fluorine-18. The present report describes the pharmacological characterisation of [18F]PR04.MZ. The ligand shows an IC50 value of 2 nM against human DAT, whereas the IC50 value against human serotonin transporter and human noradrenalin transporter are lower (110 nM and 22 nM, respectively). Furthermore, its ex vivo organ distribution, its binding profile in the rat brain and reversibility of binding were examine…
Influence of experimental diabetes on regulatory mechanisms of vascular response of rabbit carotid artery to acetylcholine
2000
Summary The purpose of this study was to analyse the influence of experimental diabetes on vascular response of rabbit carotid artery to acetylcholine (Ach). We compared the Ach-induced relaxant response of isolated arterial segments obtained from both control and diabetic animals. To assess the influence of the endothelium, this cell layer was mechanically removed in some of the arterial segments (“rubbed arteries”) from each experimental group. Ach induced a concentration-related endothelium-mediated relaxation of carotid artery from control rabbits that was significantly higher with respect to that obtained in diabetic animals. Pre-treatment with NG-nitro-L-arginine (L-NA) induced a conc…
Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 g…
2011
Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP wit…