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Toxicology Study (toxicology + study)
Selected AbstractsThe fruit fly PUB: a phagostimulation unit bioassay system to quantitatively measure ingestion of baits by individual fliesJOURNAL OF APPLIED ENTOMOLOGY, Issue 9-10 2004D. Nestel Abstract:, A bioassay to investigate quantitative phagostimulation and ingestion physiology of baits on individual fruit flies is presented. The study was undertaken using two fruit fly species: the Mediterranean fruit fly (Ceratitis capitata), a cosmopolitan insect pest, and the Ethiopian fruit fly (Dacus ciliatus), a quarantine insect in Israel. Our model bait suspension included spinosad as the toxic agent, and 1% yeast hydrolysate with 10% sucrose as phagostimulant. A preliminary toxicology study showed that the two fruit flies are highly sensitive to low concentrations of spinosad baited with this phagostimulant. The maximum concentration needed to kill 90% of the female flies was 4.2 and 8.5 p.p.m. for C. capitata and D. ciliatus, respectively. The bioassay was able to detect the ingestion of low volumes (e.g. 1 ,l) of tested solutions. The bioassay was also able to detect differences in intake of different concentrations of spinosad solutions and relate ingestion to fruit fly mortality. Additionally, the bioassay was sensitive enough to highlight differences in intake related to the physiological status of the fruit fly and fly species. The bioassay can also be used to follow ingestion kinetics of baits. We expect that this bioassay will contribute in the exploration of more efficient bait systems for fruit flies. [source] Safety Pharmacology, Toxicology and Pharmacokinetic Assessment of Recombinant Human ,-Interferon Produced from CHO-SS CellsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2006Victor E. Buckwold Here we provide an overview of our preclinical safety evaluation of the fully-glycosylated human IFN-, produced from CHO-SS cells that is currently being evaluated clinically. IFN-, was not associated with any biologically-relevant adverse effects in a series of 10 safety pharmacology experiments, in the Ames mutagenicity test, in the micronucleus test, or in intraarterial, intravenous, paravenous or subcutaneous local tolerance studies. Acute, subacute, subchronic and reproductive toxicity studies performed in cynomolgus monkeys and rats showed a toxicity profile similar to that of human , interferon (IFN-,). Except for the acute (single-dose) toxicology study, all of the other toxicity studies showed evidence for the formation of anti-IFN-, antibodies over time in the animals. These antibodies were found to neutralize IFN-, antiviral activity in vitro in a dose-dependent manner. The average pharmacokinetic parameters following a single subcutaneous dose of IFN-, in rabbits, rats and monkeys were determined and found to be similar to that of human IFN-,. These findings demonstrate that IFN-, has a safety profile consistent with that required for its use in man. IFN-, might be beneficial for the treatment of patients infected with hepatitis C virus who fail to respond to IFN-, or as a first-line treatment option. [source] Teriparatide (Biosynthetic Human Parathyroid Hormone 1,34): A New Paradigm in the Treatment of OsteoporosisBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2004Kim T. Brixen Biosynthetic human parathyroid hormone 1,34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2,3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 ,g/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged. [source] Gold (III) porphyrin complexes induce apoptosis and cell cycle arrest and inhibit tumor growth in colon cancerCANCER, Issue 19 2009Shuiping Tu MD Abstract BACKGROUND: Gold (III) compounds have exhibited favorable antitumor properties both in vitro and in vivo. In a previous study, the authors reported that the novel gold (III) complex 1a (gold 1a) exhibited strong cytotoxicity in some tumor cell lines. In the current study, the effect of gold 1a was investigated on colon cancer cells. METHODS: The cytotoxicity of gold 1a was determined by using the 3-(4,5-dimethyl-2-thihazyl)-2,5-diphenyl-2H-tetrazolium bromide method. Flow cytometry was used to detect apoptosis and cell cycle. The expression of protein was evaluated by Western blot assay. Tumor growth in vivo was evaluated in nude mice. RESULTS: Gold 1a exhibited marked cytotoxic effects in vitro to human colon cancer, and the concentration of drug required to inhibit cell growth by 50% compared with control (IC50) values ranged from 0.2 ,M to 3.4 ,M, which represented 8.7-fold to 20.8-fold greater potency than that of cisplatin. Gold 1a significantly induced apoptosis and cell cycle arrest and cleaved caspase 3, caspase 7, and poly(ADP-ribose) polymerase; released cytochrome C, and up-regulated p53, p21, p27, and Bax. In vivo, intraperitoneal injection of gold 1a at doses of 1.5 mg/kg and 3.0 mg/kg significantly inhibited tumor cell proliferation, induced apoptosis, and suppressed colon cancer tumor growth. An acute toxicology study indicated that gold 1a at effective antitumor concentrations did not cause any toxic side effects in mice. CONCLUSIONS: The current results suggested that gold 1a may be a new potential therapeutic drug for colon cancer. Cancer 2009. © 2009 American Cancer Society. [source] | ||||||||||