N-Nitrosopyrrolidine (NPyrr) and N-nitrosopiperidine (NPip) are carcinogenic and mutagenic cyclic nitrosamines. Their biotransformation by rat liver post-mitochondrial fraction into 1,4-butanediol and 1,5-pentanediol, respectively, is evaluated by determining these ultimate metabolites with a sensitive and suitable method. Their mutagenic activity towards the Salmonella typhimurium strain TA 1530 was simultaneously observed. A relationship exists between their metabolism and their mutagenicity. alpha-Hydroxylation is probably the critical metabolic metabolism of cyclic nitrosamines.

Animals↗

PubMedDate not supplied

Phase I study of paclitaxel (Taxol) plus vinorelbine (Navelbine) in patients with untreated stage IIIb and IV non-small cell lung cancer.

A dose escalation study of paclitaxel in combination with vinorelbine was conducted in 21 patients with previously untreated stage IIIb or IV non-small cell lung cancer (NSCLC). All three patients treated with the initial dose of paclitaxel 135 mg/m(2) administered as a 1-h intravenous infusion and vinorelbine 25 mg/m(2) experienced dose-limiting toxicity (febrile neutropenia). After modification of the dosing schedule, the MTD of paclitaxel was found to be 115 mg/m(2) when combined with vinorelbine 20 mg/m(2) on day 1, followed by vinorelbine 20 mg/m(2) on day 5. Partial responses were achieved in 24% of patients, with a median duration of response of 126 days (range from 84 to 484 days) and a 1-year survival rate of 42%. In conclusion, haematologic toxicity (febrile neutropenia/neutropenia) severely restricts the dosing schedule of combined paclitaxel and vinorelbine, and possibly limits anti-tumour efficacy.

Adult↗

PubMedDate not supplied

The effect of Saccharomyces cerevisiae and Aspergillus oryzae on the digestion of the cell wall fraction of a mixed diet in defaunated and refaunated sheep rumen.

The objective of this study was to determine the effect of two probiotics, Saccharomyces cerevisiae (SC) and Aspergillus oryzae (AO), without their culture medium, on the digestion of plant cell wall components in sheep that had been successively defaunated and refaunated. Six sheep fitted with large rumen cannulae were used to study 1) defaunated sheep with no probiotic, 2) defaunated sheep with SC or AO, 3) refaunated sheep with no probiotic, 4) refaunated sheep with SC or AO. The apparent digestibility of the plant cell walls was not altered (P > 0.05) by the probiotics in defaunated sheep but was increased (P < 0.05) with SC (+16%) in refaunated sheep. Simultaneously, SC stimulated the growth of the protozoal population in the rumen. As noted in most previous experiments, the positive effect of the presence of protozoa on plant cell wall digestion (P < 0.001) was confirmed here. The effect (P > 0.05) of SC or AO on in situ ADF digestion was either not significant or negative in defaunated rumens, whereas it became positive in refaunated rumen after a residence time of 12 h. The improvement of in situ ADF digestion due to the presence of protozoa was significant (P < 0.05 for NDF; P < 0.001 for ADF). However, we could not determine whether this was a direct effect of protozoa or an indirect effect operating via bacteria. The limits of the nylon bag technique for evaluating the microbial activity are discussed in relation to the ability of protozoa to enter and grow in the bags, and the pH regulation inside the bags. The pH values below 5.5 noted inside the bags can significantly alter the bacterial and protozoal populations and limit the validity of the technique. SC increased (P < 0.05) the specific activity of CMCase and xylanase of the solid-adherent bacteria (SAB) isolated from the rumen digesta of refaunated sheep. Stimulation of both the bacterial activity and protozoa numbers could explain the positive effect of SC on cell wall digestion in the rumen since the modelling of marker excretion in faeces showed that the ruminal mean retention time of hay measured from the model of Danhoa et al. was not modified (P > 0.05) by either refaunation or the presence of probiotics. AO increased (P < 0.05) the total retention time of the solid particles in the whole digestive tract and increased the ruminal liquid volume in the refaunated animals but it had no effect on the protozoa population or on the polysaccharidase activity of the SAB, which could explain the absence of effect of AO on the total digestibility of plant cell walls. Both probiotics decreased the liquid turnover in defaunated rumens (P < 0.05) but neither had any effect (P > 0.05) on this parameter after refaunation. The improvement of plant cell wall degradation in the whole digestive tract is probably due to a stimulation of digestion at the rumen level as indicated by the higher activity of the SAB in rumen digesta and the growth of protozoa.

Animal Feed↗

PubMedDate not supplied

Electrical stimulation of the human brain in epilepsy.

The concordance between the epileptogenic area as determined by intracranially recorded spontaneous seizure onset and that determined by electrically induced auras or seizures in 126 patients with medically intractable epilepsy was studied. Four to 11 multicontact depth electrodes were chronically implanted in patients as part of a preoperative investigation procedure. Localization of the epileptic area was obtained from the recording of three spontaneous seizures and from stimulation data including self-reported auras, seizures, and intracranial EEG afterdischarges recorded during an incremental stimulation sequence at all cortical pairs of contacts. Positive responses to stimulation were obtained in 63% of patients. Concordance between spontaneous and induced auras or seizures was greater than 90% with single unilateral foci and less with multiple foci. Stimulation data reliably predicted the resection area in unilateral and bilateral temporal foci but not in other locations. Afterdischarge thresholds were not reliable predictors of the spontaneous seizure focus. The intracranial stimulation procedure used appears to provide useful confirmatory and complementary localizing information in relation to that obtained from spontaneous seizures.

Brain↗

PubMedDate not supplied

Biochemical basis for the resistance of guinea-pig and monkey to the carcinogenic effects of arylamines and arylamides.

1. Ag.l.c. assay for N-hydroxy-2-acetamidofluorene has been modified to measure both N-hydroxy-2-acetamidofluorene and N-hydroxy-2-aminofluorene. 2. Like guinea-pig, monkey N-hydroxylates both 2-aminofluorene and 2-acetamido-fluorene. The N-hydroxy metabolites are rapidly further metabolized even in the presence of inhibitors of deacetylase. The exact nature of this further metabolism is still unknown. Preliminary evidence indicates that, at least in the guinea-pig, 7-hydroxy-2-acetamidofluorene may be a metabolite of N-hydroxy-2-acetmidofluorene. 3. 3-Methylcholanthrene, 7,8-benzoflavone and miconazole, which have been shown to inhibit guinea-pig liver microsomal N-hydroxylase, do not significantly inhibit the monkey liver enzyme. 4. 2-Acetamidofluorene, which inhibits the guinea-pig liver microsomal N-hydroxylation of 2-aminofluorene in vitro, activates the enzyme from monkey liver. This activation, which is dose-dependent, appears to be allosteric. 5. Both guinea-pig and monkey are more efficient in N-hydroxylating 2-aminofluorene than 2-acetamidofluorene. The affinity (in term of apparent KM) of the guinea-pig liver enzyme is 4 times greater than the affinity of the monkey liver enzyme.

2-Acetylaminofluorene↗

PubMedDate not supplied

[Measurement of cardiac glycosides in biological fluids by atomic absorption spectrophotometry].

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Cardiac Glycosides↗