Search results for "TOXICITY"
showing 10 items of 2261 documents
Metabolic activity of fresh and cryopreserved cynomolgus monkey (Macaca fascicularis) hepatocytes
2000
1. The effect of cryopreservation on the metabolic capacity of monkey hepatocytes over 4 h in suspension and 24 h in culture was determined. Hepatocytes were diluted in a buffer containing 10% DMSO and frozen in a computer-controlled chamber. 2. Initial ethoxyresorufin and ethoxycoumarin O-deethylase (ECOD) activities were the same in fresh and cryopreserved (CP) hepatocytes. ECOD activity in suspensions declined over 4 h but was the same in fresh and CP hepatocytes. 3. The formation of testosterone hydroxy (OHT) metabolites (namely 6beta-OHT, 2beta-OHT, 16beta-OHT, 16alpha-OHT, 15beta-OHT, 2alpha-OHT and 6beta-OHT) was unaffected by cryopreservation. The loss of OHT activities over 4 h in …
Phenylamides of 1-Phenyl (or Methyl)-5-benzamidopyrazole-4-carboxylic Acid as Vratizolin Analogs with Analgesic and Antiinflammatory Activities
2001
A number of phenylamides of 5-benzamidopyrazole-4-carboxylic acid were prepared in 50-80 % yields from 1-phenyl (or methyl) 6-phenylpyrazolo[3,4-d]1,3-oxazin-4(1H)-ones and aniline derivatives. All the compounds were tested for their analgesic and antiinflammatory activities, as well as for their ulcerogenic potential and acute toxicity. Some derivatives, when compared to phenylbutazone, proved more active in the tests for analgesie and antiexudative activities, but less active in the carrageenin paw oedema test. The compounds proved to posses marginal or no ulcerogenic effect, as well as low systemic toxicity.
Synergistic effect of peplomycin in combination with bleomycin on L5178y mouse lymphoma cells in vivo.
1984
Studying the treatment of NMRI mice with ip injections of bleomycin (BLM) for 5 days we found an approximate LD50 of 35 mg/kg; the toxicity of peplomycin (PEP) was slightly higher (LD50: approximately 25 mg/kg). The effect of the two drugs on growth of L5178y mouse lymphoma cells in NMRI mice was examined. BLM alone caused at a concentration of 2.5 mg/kg an almost complete inhibition of tumor cell growth; the same effect was determined with 1 mg PEP/kg. At these concentrations the drugs caused an increase of the survival time of 110% (BLM) or 104% (PEP). Given in combination, one-sixth of the optimal doses yielded an 100% increase of the median survival time. These results indicate a signif…
Toxicity of used orthodontic archwires assessed by three-dimensional cell culture
2006
The aim of the present study was to determine whether used orthodontic wires made of different materials cause toxicity and loss of viability on three-dimensional (3D) cell cultures. Three types of orthodontic wires, stainless steel, Nitinol, and TMA (n = 9) which had been used clinically in fixed appliances for a period of 1 month, were retrieved at random from five patients. Both upper and lower archwires were collected and subjected to two different protocols: to assess toxicity, two pieces of each wire were placed on 3D cell cultures (reconstituted human epithelium); to investigate the possibility of cell damage, the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) ass…
Acute toxicity of dichlorvos to Aphanius iberus (Cuvier & Valenciennes, 1846) and its anti-cholinesterase effects on this species
2008
This study evaluates the toxic effects of the organophosphate pesticide (OP) dichlorvos to the endangered Iberian toothcarp (Aphanius iberus). To this end, the lethal toxicity of dichlorvos based on 96 h-LC50 bioassays was determined in saline water (50 g/L), and in vivo effects of dichlorvos on cholinesterase (ChE) activity were investigated in adult female and male specimens. The 96 h-LC50 value determined by probit analysis was 3.17 mg/L (95% confidence limits: 1.34-3.97). The characterisation of the ChE using different substrates and specific inhibitors was also carried out in head and muscle tissues. Acetylthiocholine was the substrate preferred by both head and muscle ChE in males and…
Phase II dose escalation study of caspofungin for invasive Aspergillosis.
2011
ABSTRACT Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics w…
Prenatal cocaine alters later responses to morphine in adult male mice.
2006
Mice prenatally exposed to cocaine (25 mg/kg), physiological saline or non-treated during the last 6 days of pregnancy were evaluated as adults for the rewarding properties of 2 mg/kg of morphine, using the conditioned place preference (CPP) procedure. Likewise, isolated animals underwent a social interaction test with conspecifics after receiving the same morphine dose. Unlike control or animals pre-treated with saline, subjects prenatally treated with cocaine did not develop CPP with this dose of morphine. Only cocaine-exposed animals showed increased threat, avoidance and fleeing during the social encounter. No differences in motor effects of morphine were observed. Analysis of monoamine…
Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors
1992
AbstractPrevious experiments in our laboratory suggested that ammonium toxicity could be mediated by the NMDA type of glutamate receptors. To assess this hypothesis we tested if MK-801, a specific antagonist of the NMDA receptor, is able to prevent ammonium toxicity. Mice and rats were injected i.p. with 12 and 7 mmol/kg of ammonium acetate, respectively, 73% of the mice and 70% of the rats died. However, when the animals were injected i.p. with 2 mg/kg of MK-801, 15 min before ammonium injection, only 5% of the mice and 15% of the rats died. The remarkable protection afforded by MK-801 indicates that ammonia toxicity is mediated by the NMDA receptor.
BPA, an Energy Balance Disruptor
2014
International audience; Bisphenol A (BPA) is used extensively in the world and is present in a diverse range of manufactured articles including dental resins, polycarbonate plastics, and the inner coating of food cans. It is a high volume chemical, with global production at 3.6 × 109 kg per year. BPA was identified as a high priority for assessment of human health risk because it was considered to present greatest potential for human exposure. Most studies of the health effects of BPA have focused on endocrine disruption leading to reproductive toxicity, but it displays additional side effects, including liver damage, disrupted pancreatic β-cell function, thyroid hormone disruption, and obe…
Relationship of curative surgery on natural killer cell activity in colorectal cancer.
1996
Aim of this study has been to evaluate natural killer (NK) activity in patients with colorectal tumors before and after curative surgery.Forty colorectal cancer patients without distant metastases were stratified according to American Joint Committee on Cancer/International Union Against Cancer staging system into three categories: Stage I (n = 12), Stage II (n = 15), and Stage III (n = 13). All of them underwent curative resection, and there were no major postoperative complications. Venous blood samples were obtained preoperatively, at surgical wound closure, and on the 1st, 7th, and 21st postoperative days. Mononuclear cells were isolated over Ficoll-Hypaque (Lymphoprep, Nycomed Pharma A…