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Biomedical subjects

F De Matteis

Publications and source records attributed to F De Matteis.

126 records · Page 7Linked to original sources
PubMed1968

Stimulation of liver cholesterol synthesis by actinomycin D.

1. An eightfold increase in the incorporation of [2-(14)C]acetate into liver cholesterol in vivo was observed 24hr. after starved rats had been given actinomycin D (0.5mg./kg. of body wt.). Liver cholesterol radioactivity declined faster in the treated animals, suggesting a greater rate of cholesterol turnover. 2. Liver slices from treated animals showed a tenfold increase in the incorporation of [2-(14)C]acetate into cholesterol; conversion into CO(2) and into fatty acids was less markedly increased, and conversion into ketone bodies was not significantly affected. 3. The patterns of conversion into liver cholesterol in vivo of the lactone and the sodium salt of mevalonic acid differed markedly. The former was converted at a faster rate and to a greater extent than the latter. Treatment with actinomycin D increased the conversion of both forms of mevalonic acid into liver cholesterol, but only to a small extent. 4. Stimulation of the incorporation of acetate into cholesterol occurred at 4hr. after the administration of actinomycin D but not at 2hr. The response was abolished by the simultaneous administration of dl-ethionine or puromycin. 5. Pre-feeding with a cholesterol-rich diet greatly diminished the stimulation of conversion of acetate into cholesterol caused by actinomycin D, though it did not completely suppress it. Adrenalectomized animals responded to the drug, but much less markedly. 6. It is concluded that actinomycin D stimulates the synthesis of cholesterol in the liver at a stage in the pathway before mevalonic acid, by a mechanism that probably requires protein synthesis. A likely site would be the beta-hydroxy-beta-methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Some possible mechanisms by which the drug may lead to increased activity of this enzyme are considered.

Acetates↗
PubMedDate not supplied

Peroxylated and hydroxylated uroporphyrins: a study of their production in vitro in enzymic and chemical model systems.

In previous work certain hydroxylated and peroxylated derivatives of uroporphyrin (URO) have been isolated from the urine of patients suffering from porphyria. We have now investigated the mechanism of production of these oxygenated derivatives of URO, using both enzymic and chemical model systems and also the effect of exposure to light during reoxidation of uroporphyrinogen (URO'gen). When URO'gen was incubated with haemolysates, peaks with the same retention times as peroxyacetic acid URO, meso-hydroxy URO and beta-hydroxypropionic acid URO were all detected. The first of these was formed in sufficient amounts to allow its characterization by mass spectrometry. Under these conditions, peroxyacetic acid derivatives of heptacarboxylate and pentacarboxylate porphyrins could also be produced from the corresponding porphyrinogens, but no peroxylated product could be obtained from coproporphyrinogen (COPRO'gen, where no acetic acid side chains are present) or from the fully oxidized URO. Similar results were obtained on re-oxidation of URO'gen in the xanthine oxidase-xanthine system and in the presence of hydrogen peroxide/Fe-EDTA (ethylenediamine-tetraacetic acid) and here again no peroxylated product could be detected from either COPRO'gen or URO. Finally, formation of peroxyacetic acid URO could be demonstrated during photo-oxidation of URO'gen and this was followed by light-induced loss of both URO and its peroxylated derivative. It is concluded that the oxygenated derivatives arise from the action of reactive oxygen species on the porphyrinogens (rather than the porphyrins), with one of the acetic acid side chain serving as the preferential (or exclusive target) for peroxylation.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Species differences in the metabolic activation of tamoxifen into genotoxic derivatives: risk assessment in women.

Rats and Rhesus monkeys are compared in their response to tamoxifen treatment, with particular reference to tamoxifen-related liver DNA damage and bioactivation of tamoxifen by isolated microsomes in vitro. Monkeys, treated with tamoxifen, accumulate in their livers a metabolite of tamoxifen, N,N-didesmethyl tamoxifen, with powerful inhibitory activity on cytochrome P450-dependent drug metabolism. The accumulation of this metabolite in the monkeys may limit the cytochrome P450-dependent conversion of tamoxifen into reactive derivatives and, in this way, protect against the formation of DNA adducts. This metabolite is also found in the liver and serum of patients taking tamoxifen, but more work is needed to determine whether inhibition of tamoxifen bioactivation also exists in the human patient in vivo and, if so, to what extent and in which organ.

Animals↗
PubMedDate not supplied

[The treatment with biosynthetic growth hormone (GH) of familial short stature].

The effect of growth hormone (GH) treatment in non-GH deficient subjects has been amply studied over the past few years. Although the results of these studies are encouraging, there are still no definitive data since the findings are not comparable due to the different characteristics of the populations examined. In the present study the authors examined the following parameters: stature, height SDS, growth rate, bone age and final height prediction according to Tanner, pubertal stage, before and after treatment with biosynthetic GH at a dose of 1.4 IU/kg of bodyweight for 12 months. The population treated consisted of 10 subjects (5 males and 5 females) aged between 7.3 and 9.5 years old, all prepubertal, with "familial short stature", selected according to the following criteria: stature below the 3rd centile, normal growth rate, normal GH response to stimuli using clonidine and insulin, correlation with parental stature between 25th and 75th centile, bone age correlated to chronological age, absence of other pathologies. After 12 months height SDS moved from -2.75 +/- 0.26 to -2.23 +/- 0.25 (p < 0.5); the growth rate changed from 5.75 +/- 0.63 to 6.66 +/- 0.56 (p < 0.05). No abnormal acceleration of bone age as observed: it moved from 8.2 +/- 0.62 to 9.5 +/- 0.72; all subjects continued to be prepubertal. The expected final stature changed from 154 +/- 2.38 to 159 +/- 0.7 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMedDate not supplied

[THe video laparoscopic experience of the general surgeon in cholecystectomy in childhood].

Despite the exponentially increasing number of laparoscopic cholecystectomies on adults to date, there is a paucity of reports in the literature about this new technique in pediatric patients. From September 1992 to February 1995, 140 patients underwent laparoscopic cholecystectomy. Since July 1993, in our institution, five pediatric patients (three females and two males) with a diagnosis of cholelithiasis underwent laparoscopic cholecystectomy. The age of the patients ranged from 6 to 15 years (mean 8.8 years) and they weighed 18-58 kg (mean 28.4 kg). All five patients had biliary cholic and ultrasound evidence of cholelithiasis. One patient had associated hematological disease (sickle cell disease). All 5 children were operated using the laparoscopic approach technique. Operative cholangiography was performed in cases with ductal and vascular intraoperative anatomy unclear. No operation was converted to open cholecystectomy. Intraoperative cholangiography was performed successfully (100%). The mean time of surgery was 50.2 minutes (range from 38 to 68). There were no operative complications. The mean hospital stay was 2.2 days (range 2 to 3 days). All five returned to their activity within a week. No long-term complications were seen in all patients throughout an average follow-up period of 10.6 months (range 8-14). The benefits of laparoscopic cholecystectomy in children are clear and obvious. It is safe and effective and should now be the treatment of choice for cholelithiasis in pediatric patients.

Adolescent↗