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Jeffrey I Everitt - One of the best experts on this subject based on the ideXlab platform.
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promotion by sodium Barbital induces early development but does not increase the multiplicity of hereditary renal tumors in eker rats
Carcinogenesis, 2000Co-Authors: Douglas C Wolf, Thomas L Goldsworthy, Derek B Janszen, R Harden, E M Donner, C S David, Jeffrey I EverittAbstract:Induced cell proliferation is important in the mode of action of many non-genotoxic renal carcinogens. Since Tsc2 mutant (Eker) rats are genetically predisposed to the development of renal cell tumors, they provide a useful animal model in which to study the action of renal carcinogens. Sodium Barbital was used as a model non-genotoxic renal carcinogen to test whether a concentration that increased renal tubular proliferation without severe nephrotoxicity would enhance tumor induction in a hereditary tumor model. First, a subchronic concentration-response study was conducted in wild-type male Long-Evans rats to determine increased cell proliferation without severe nephrotoxicity. Rats were dosed with sodium Barbital in the feed at 0, 50, 250, 500, 1000, 2000 or 4000 p.p.m. for 3 or 8 weeks. Cell proliferation within the cortex and nephrotoxicity were quantitated. Enhanced proliferation with minimal nephrotoxicity occurred at 500 p.p.m. A second study was conducted in male Tsc2 mutant rats given sodium Barbital in the feed at 0, 100 or 500 p.p.m. from 9 weeks of age to either 6 or 12 months of age. An additional group of rats was treated with sodium Barbital for 6 months and then provided control feed until 12 months of age. Rats necropsied at 6 months of age had a concentration-dependent increase in preneoplastic and total renal lesions. Sodium Barbital-treated rats necropsied at 12 months of age had numbers of lesions that were not different from controls. Total combined preneoplastic and neoplastic lesions in the 6 month, high dose group was the same as the 12 month control group. These data show that sodium Barbital caused progression to the stage of spontaneous renal lesions in Tsc2 mutant rats but did not increase their overall number. These data suggest that enhanced cell proliferation without significant cytotoxicity exerted a promotional influence in this hereditary model.
Miwa Misawa - One of the best experts on this subject based on the ideXlab platform.
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EFFECTS OF NIFEDIPINE ON PHYSICAL DEPENDENCE ON Barbital OR DIAZEPAM IN RATS
The Journal of toxicological sciences, 1995Co-Authors: Tsutomu Suzuki, Hirokazu Mizoguchi, Hiroshi Motegi, Hideto Awano, Miwa MisawaAbstract:The effects of nifedipine on the development of physical dependence on Barbital and diazepam in rats were examined using the drug-admixed food method. Rats were chronically treated with either Barbital- or Barbital in combination with nifedipine-admixed food for 28 days, and with either diazepam- or diazepam in combination with nifedipine-admixed food for 26 days, on schedules of gradually increasing doses of Barbital or diazepam. Withdrawal was conducted by substituting normal food for drug-admixed food on the last day of the treatment. Co-administration of nifedipine with Barbital potentiated body weight loss and withdrawal scores after the termination of Barbital treatment. However, the withdrawal signs after the termination of diazepam treatment were not affected by co-administration of nifedipine with diazepam. These results suggest that nifedipine potentiates the development of physical dependence on Barbital but not diazepam. It is known that co-administration of dihydropyridine derivative nitrendipine suppresses the development of physical dependence on ethanol. Basing on the differences in sensitivity of central depressants, barbiturates, benzodiazepines and ethanol, to three types of voltage-dependent Ca2+ channels, such as L-, N- and T-types studied so far, the development of physical dependence on central depressants may be modified differently by L-type Ca2+ channel blockers, corresponding to respective depressants.
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Effects of flunarizine and diltiazem on physical dependence on Barbital in rats
Pharmacology biochemistry and behavior, 1993Co-Authors: Tsutomu Suzuki, Hirokazu Mizoguchi, Hideaki Noguchi, Toshio Yoshii, Miwa MisawaAbstract:Abstract The effects of flunarizine and diltiazem both on development of physical dependence on Barbital and on Barbital withdrawal signs in rats were examined using the drug-admixed food (DAF) method. Rars were chronically treated with Barbital or Barbital in combination with flunarizine (fixed at 1.5 mg/g of food) or diltiazem (fixed at 0.75 mg/g of food)-admixed food on the schedule of gradually increasing doses of Barbital. Motor incoordination during the treatment was potentiated by coadministration of flunarizine, but not by coadministration of diltiazem. After the termination of drug treatment, the body weight loss and withdrawal scores were significantly suppressed in the group coadministered flunarizine, but not in that coadministered diltiazem. There were no significant differences in plasma Barbital levels after the withdrawal between groups. In the substitution test, flunarizine (20 and 40 mg/kg, IP) significantly suppressed the body weight loss and withdrawal scores after the withdrawal, but diltiazem (20 mg/kg, IP) did not. These results indicated that flunarizine suppressed both the development of physical dependence on Barbital and Barbital withdrawal signs, mainly according to the suppression of convulsions, but not diltiazem, which is known to poorly penetrate into the brain. Therefore, the present findings suggest that central calcium channels may be involved in both the development of physical dependence on Barbital and the appearance of Barbital withdrawal signs.
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Susceptibility to, tolerance to, and physical dependence on ethanol and Barbital in two inbred strains of rats.
General pharmacology, 1992Co-Authors: Tsutomu Suzuki, Hiroshi Motegi, Kokichi Otani, Yoko Koike, Miwa MisawaAbstract:Abstract 1. 1. Ethanol-induced sleep time was significantly longer in F344 than LEW rats. However, there is no difference in Barbital-induced sleep time between F344 and LEW. 2. 2. Development of tolerance to ethanol-induced motor impairment was slightly faster in F344 than in LEW rats. While, LEW rats more easily developed tolerance to the impairment by Barbital in comparison with F344 rats. 3. 3. F344 and LEW rats were chronically treated with liquid diet containing ethanol or with Barbital-admixed food. After the termination of ethanol and Barbital treatments, various withdrawal signs occurred in F344 rats, including tremor and convulsions, whereas LEW rats showed no convulsions. Withdrawal scores of ethanol and Barbital were significantly higher in F344 than in LEW rats. 4. 4. These results suggest that strain differences in physical dependence on ethanol and Barbital may be mainly influenced by the susceptibility to ethanol and the development of tolerance to Barbital, respectively.
K B J Franklin - One of the best experts on this subject based on the ideXlab platform.
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Systemic and intracerebroventricular administration of sodium Barbital induced a place preference in rats.
Behavioural pharmacology, 2003Co-Authors: Jennifer M. Bossert, R S Biskin, K B J FranklinAbstract:We have shown previously that 15 mg/kg pentoBarbital induces a conditioned place preference (CPP), but it is unsuitable for intracranial administration. Since the long-acting barbiturate, sodium Barbital, is soluble at a neutral pH, we tested whether it would induce a CPP when administered centrally. Furthermore, because Barbital has a long duration of action, and because we obtained a significant CPP to systemically administered Barbital using 30-minute conditioning trials, we tested whether longer conditioning trials would produce a more robust CPP. Using a three-compartment apparatus and an unbiased procedure, we found that systemic administration of Barbital induced a significant CPP at 8 and 24 mg/kg, but not 2.7 or 72 mg/kg (i.p.). When rats were conditioned to 24 mg/kg Barbital for conditioning trials of (1/2), 1, 3, or 6 hours, only the 30-min conditioning trial produced a CPP. Finally, 240 and 480 microg intracerebroventricular (ICV) Barbital induced a significant CPP, but 60 or 120 microg did not. These findings suggest that: (1) like pentoBarbital, Barbital has reinforcing properties measured in the CPP test; (2) the CPP is impaired, rather than enhanced, by increasing the duration of drug-context pairing; and (3) the reinforcing effects of barbiturates are centrally mediated.
Douglas C Wolf - One of the best experts on this subject based on the ideXlab platform.
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promotion by sodium Barbital induces early development but does not increase the multiplicity of hereditary renal tumors in eker rats
Carcinogenesis, 2000Co-Authors: Douglas C Wolf, Thomas L Goldsworthy, Derek B Janszen, R Harden, E M Donner, C S David, Jeffrey I EverittAbstract:Induced cell proliferation is important in the mode of action of many non-genotoxic renal carcinogens. Since Tsc2 mutant (Eker) rats are genetically predisposed to the development of renal cell tumors, they provide a useful animal model in which to study the action of renal carcinogens. Sodium Barbital was used as a model non-genotoxic renal carcinogen to test whether a concentration that increased renal tubular proliferation without severe nephrotoxicity would enhance tumor induction in a hereditary tumor model. First, a subchronic concentration-response study was conducted in wild-type male Long-Evans rats to determine increased cell proliferation without severe nephrotoxicity. Rats were dosed with sodium Barbital in the feed at 0, 50, 250, 500, 1000, 2000 or 4000 p.p.m. for 3 or 8 weeks. Cell proliferation within the cortex and nephrotoxicity were quantitated. Enhanced proliferation with minimal nephrotoxicity occurred at 500 p.p.m. A second study was conducted in male Tsc2 mutant rats given sodium Barbital in the feed at 0, 100 or 500 p.p.m. from 9 weeks of age to either 6 or 12 months of age. An additional group of rats was treated with sodium Barbital for 6 months and then provided control feed until 12 months of age. Rats necropsied at 6 months of age had a concentration-dependent increase in preneoplastic and total renal lesions. Sodium Barbital-treated rats necropsied at 12 months of age had numbers of lesions that were not different from controls. Total combined preneoplastic and neoplastic lesions in the 6 month, high dose group was the same as the 12 month control group. These data show that sodium Barbital caused progression to the stage of spontaneous renal lesions in Tsc2 mutant rats but did not increase their overall number. These data suggest that enhanced cell proliferation without significant cytotoxicity exerted a promotional influence in this hereditary model.
Javier Barriosgonzalez - One of the best experts on this subject based on the ideXlab platform.
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biochemical mechanism of the effect of Barbital on rifamycin b biosynthesis by amycolatopsis mediterranei m18 strain
Journal of Bioscience and Bioengineering, 2003Co-Authors: Armando Mejía, G Viniegragonzalez, Javier BarriosgonzalezAbstract:Abstract It is well known that 5,5-diethylbarbituric acid (Barbital) in the culture medium can stimulate the production of rifamycin B by Amycolatopsis mediterranei , particularly in industrial processes. However, the mechanism by which Barbital exerts this effect is unknown. Results in this work show that the Barbital effect is only evident under low aeration conditions (50-ml microfermentors with 7 ml of medium, 0.08 l /h air flow). Under these conditions, cultures with Barbital showed similar CO 2 production (in relation to a control without Barbital), but higher oxygen uptake indicated that the extra O 2 consumed was used in the increased rifamycin biosynthesis. Moreover, using a resting cell system where no antibiotic is produced, it was possible to show that Barbital inhibits the respiratory chain, since O 2 uptake decreased by 30%. Finally, we present biochemical results that suggest that a cytochrome P450-type monoxygenase, which can use atmospheric oxygen, is induced by Barbital in an industrial-type strain of A. mediterranei .
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overproduction of rifamycin b by amycolatopsis mediterranei and its relationship with the toxic effect of Barbital on growth
The Journal of Antibiotics, 1998Co-Authors: Armando Mejía, Javier Barriosgonzalez, G ViniegragonzalezAbstract:A novel method for selecting overproducing strains of rifamycin B was developed. This technique involves the use of lysozyme and the effect of Barbital on the growth of A. mediterranei. Complete medium added with glycine and Barbital was inoculated with mutagenized mycelium, incubated for 48 hours and treated with lysozyme. The lysozyme resistant mycelium was washed with dilute detergent. Complete medium with glycine but without Barbital was inoculated with the washed mycelium. Protoplasts were obtained and regenerated and the colonies were picked and seeded on Bennet agar plates with and without Barbital. Two selected mutants were sensitive to 0.5% Barbital producing 200% more rifamycin than the parental strain. In addition, 30 Barbital resistant mutants were isolated and their production level was lower than the one observed with the parental strain. These results suggest that the effect of Barbital on secondary metabolism (rifamycin production) is related to its effect on primary metabolism.