n-3 polyunsaturated fatty acids decrease mucosal/epidermal reactions and enhance antitumour effect of ionising radiation with inhibition of tumour angiogenesis.

The purpose of this study was to evaluate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on normal tissue (lip mucosa) and tumour growth when combined with ionising radiation. The oral region (snout) of C57 black mice was irradiated with 16.5 Gy and n-3 PUFAs (100 microl) were injected intravenously for 2 weeks. After exposure to irradiation, the degree and duration of the acute reactions decreased significantly when mice were treated with n-3 PUFAs as compared to the control group. Interestingly, the range of the reactions in the n-3 PUFAs-treated group compared favourably to the group receiving amifostine (27.5 mg/kg i.v.). the effect of n-3 PUFAs was further evaluated in HEP-2 human carcinoma xenograft transplanted in nude mice. An inhibition of tumour growth was observed when mice were treated with n-3 PUFAs alone and this effect was maximal when combined with irradiation. Similar results were obtained using eicosapentaenoic acid. The effect of n-3 PUFAs was associated with inhibition of angiogenesis and tumour proliferation, and significantly decreased expression of cyclooxygenase-2. In conclusion, n-3 PUFAs administration decrease mucosal response, while moderately enhancing the antitumour effect of irradiation. The magnitude of the differential effect suggests that n-3 PUFAs need to be further investigated in the clinic.

Low hepatic iron concentration: evaluation of two complementary methods, colorimetric assay and iron histological scoring.

AIMS: To validate a method of assessment of low hepatic iron concentration based on a biochemical colorimetric assay plus histological scoring. METHODS: The within-day and day to day precision of the iron colorimetric assay was determined on frozen rat liver. The coefficient of variation (CV) of iron measurement in two separate samples from the same liver was determined for 21 deparaffinised human biopsies. The intra- and interlaboratory variability of the colorimetric assay and histological scoring were assessed on 38 deparaffinised liver biopsies. RESULTS: For the within-day test, the CV was 11% (5.1 (0.6) mumol/g dry weight (dw), mean (SD) iron concentration). For the day to day test, the CV was 19.5% (8.2 (1.6) mumol/g dw). The CV was 14.7% for iron concentration determined in two separate samples from the same liver. By correlation and kappa concordance tests, the intra- and interlaboratory variability of the hepatic iron colorimetric assay and iron histological scoring was slight. Absence of stainable iron corresponded to a liver iron concentration < or = 20 mumol/g dw. CONCLUSIONS: A combination of two complementary methods, colorimetric measurement and histological scoring, is an accurate and reliable way of determining low iron concentrations in deparaffinised human liver biopsies. In secondary haemosiderosis, such methods would be essential for investigating the role of low iron overload in fibrogenesis and during the response to antiviral treatment in chronic viral hepatitis.

Hypnotic relaxation: a new sedative tool for colonoscopy?

Sedation is often justified in patients requiring colonoscopy. We investigated the potential usefulness of hypnotic relaxation in 13 women and 11 men (median age, 43 years; range, 22-67) for whom other forms of anesthesia were not available. Hypnotic relaxation resulted in moderate or deep sedation in 12 patients (nine women; p < 0.05). In the patients in whom hypnosis was successful, pain was less intense than in patients in whom hypnosis was unsuccessful (p < 0.001). In addition, all colonoscopies were completed in the successful group, versus 50% in the unsuccessful group (p < 0.05). The patients in the successful group all agreed to another examination under the same conditions, whereas only 2% in the unsuccessful group agreed (p < 0.001). Our study suggests that, in a subgroup of hypnotizable patients, hypnotic relaxation may be a safe alternative to drug sedation and merits further study.

Evidence for the role of ammonia in the intracerebral transfer and metabolism of tryptophan.

After portacaval shunt in the rat, the transport of tryptophan and other neutral amino acids across the blood-brain barrier is enhanced. To determine the role of NH3 in the intracerebral transfer of tryptophan and serotonin metabolism, solutions containing either saline or NH3 or tryptophan or NH3 + tryptophan together were infused, respectively, into the internal carotid artery of rats in order to achieve blood levels similar to those observed after liver ischemia. After tryptophan infusion, a significant increase in the hypothalamic levels of tryptophan and 5-hydroxyindoleacetic acid was observed. A similar increment was found after NH3 infusion. NH3 + tryptophan infusion induced a significant increment in hypothalamic tryptophan and 5-hydroxyindoleacetic acid levels which were 2-fold greater than after tryptophan infusion. There was no significant change in 5-hydroxytryptamine levels in any of these experiments. Glutamine levels increased significantly after NH3 infusion. When tryptophan and NH3 were infused simultaneously, a significant reduction in glutamine levels occurred. These results cannot be explained by any modification of cerebral blood flow nor of the cerebral intercellular pH. Our data suggest that NH3 enhances the transfer of tryptophan across the blood-brain barrier and thus stimulates serotonin metabolism. The mechanism by which tryptophan transfer across the blood-brain barrier is facilitated is unknown. The reduction in glutamine levels in the hypothalamus when NH3 and tryptophan are infused together may be explained either by an inhibition of synthesis or by an intercellular influx of neutral amino acids and an efflux of glutamine as suggested by James et al.