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Biomedical subjects

R Fiorio

Publications and source records attributed to R Fiorio.

At least 19 recordsLinked to original sources
PubMed2000

Antimutagenesis studies of magnesium and calcium salts.

Magnesium is a microelement that is essential for biological functions and particularly for cellular metabolism. It has a central role in protein, lipid, carbohydrate, and nucleic acid synthesis, and it is important for muscular physiology and nerve excitability. Magnesium has an important role in the stability of biological membranes, it controls immune phenomena, and it activates over 300 enzymes. However, the mechanism of action of magnesium salts has not been well investigated and, in particular, its antimutagenesis properties and its effects in the detoxification of free radicals need further study. We investigated the effect of magnesium chloride, sulphate, carbonate, and oxide on the yeast Saccharomyces cerevisiae D7 strain, to evaluate their ability to protect against genotoxic damage. We found that magnesium salts induced antimutagenic effects in the cells harvested in the logarithmic phase by decreasing the induction of hydrogen peroxide. This, however, did not occur in the stationary phase. We also studied calcium salts of the type corresponding to those of magnesium and their protective role against the oxidative damage of free radicals and enzymatic activities, such as catalase, glutathione peroxidase, and superoxide dismutase, which are involved in antioxidative defenses.

Antimutagenic Agents↗
PubMed1996

Antimutagenesis and anticancer effects.

Cancer development is a multistage process wherein mutational events play an important role. Various antimutagen components, in particular magnesium and selenium, have been reported to have anticarcinogenic properties. These two oligoelements display different behaviors according to their concentrations. The different effects of magnesium and selenium depend on the different mechanisms of cell absorption. The importance of antimutagenesis studies in cancer prevention is reported and a review of the basic mechanisms operative in antimutagenesis, including some data on known antimutagens, is made.

Animals↗
PubMed1994

Effects of spermine on formation of HGPRT- mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C in V79 Chinese hamster cells.

Spermine is a polyamine found in bacteria, animal, and plant tissues. It is involved in a variety of biological processes, and its interaction with DNA stabilizes the secondary structure of the double helix. Spermine is one of the first reported antimutagens, reducing the mutation rate in several prokaryotic test systems, while in eukaryotic organisms conflicting results have been obtained. In light of the significant antimutagenic effect of spermine, it is important to evaluate its activity in mammalian cells in culture. The present study was undertaken to evaluate the ability of spermine to suppress the level of HGPRT- mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C. Spermine reduced the mutation frequency induced by ethylmethanesulfonate and methylmethanesulfonate but did not affect survival; with mitomycin C survival was reduced but mutation rate was not influenced.

Alkylation↗
PubMed1994

Effects of cinnamaldehyde on survival and formation of HGPRT- mutants in V79 cells treated with methyl methanesulfonate, N-nitroso-N-methylurea, ethyl methanesulfonate and UV light.

The effects of the antimutagenic flavoring cinnamaldehyde on the induction of HGPRT- mutants by methyl methanesulfonate (MMS), N-nitroso-N-methylurea (MNU), ethyl methanesulfonate (EMS) and UV light was investigated in the Chinese hamster V79 cell line. Cinnamaldehyde did not show any mutagenic or toxic effects in this experimental system by itself and did not modify mutation frequency when given to cells simultaneously with chemical mutagens. Under these conditions, the cytotoxicity of MMS, but not that of MNU and EMS, was increased. Cell viability was also reduced in MNU-, EMS-, or UV light-pretreated cells when they were postincubated in the presence of cinnamaldehyde. Moreover, cinnamaldehyde reduced the frequency of mutations induced by MMS but not by the other mutagens. The results obtained suggest that cinnamaldehyde inhibits some cellular function(s) promoting the repair of a variety of different cytotoxic lesions. At the same time, stimulation by cinnamaldehyde of an error-free DNA repair mechanism acting on MMS-induced mutagenic damage was indicated.

Acrolein↗
PubMed1992

Influence of cinnamaldehyde on UV-induced gene conversion and point mutation in yeast: effect on protein synthesis.

The activity of cinnamaldehyde (CIN), a bioantimutagen in bacterial systems, was tested in the D7 strain of yeast Saccharomyces cerevisiae. Yeast cells were UV-irradiated and post-incubated in liquid growth medium for 2 and 4 h with different concentrations of cinnamaldehyde. During the post-incubation period, DNA-damage-specific functions may be induced. This in turn may affect the genotoxicity and in fact a weak decrease in UV-induced convertant and revertant frequencies was observed after 4 h of post-incubation. The presence of CIN in the growth medium increased the UV-induced gene conversion and reversion. The addition of cycloheximide abolished this effect. To evaluate the CIN effect on protein synthesis, extracts of cells UV-treated and post-incubated for 2 h in the presence of 35S-methionine were performed. SDS-gel electrophoresis demonstrated the inhibitory effect of CIN on a UV-specific protein. This work suggests that CIN might interfere with DNA-damage-inducible systems although it did not exert an antimutagenic activity in our experimental conditions.

Acrolein↗
PubMed1991

Genotoxicity of vanadium compounds in yeast and cultured mammalian cells.

The ability of vanadium compounds to induce genetic activity was investigated in D7 and D61M strains of Saccharomyces cerevisiae and in Chinese hamster V79 cell line. In our previous work, ammonium metavanadate (pentavalent form, V5) induced mitotic gene conversion and point reverse mutation in the D7 strain of yeast. The genotoxicity was reduced by the presence of S9 fraction, which probably reduced pentavalent vanadium to the tetravalent form. In the present study, vanadyl sulfate (tetravalent form, V4) induced no convertants and revertants in yeast cells harvested from stationary growth phase. With yeast cells from logarithmic growth phase, which contain high levels of cytochrome P-450, a significant increase in genetic effects was observed. Further experiments, performed by treating cells harvested from logarithmic growth phase in the presence of cytochrome P-450 inhibitors, indicated that the monooxygenase system influenced the genotoxicity of metavanadate while the genetic activity of vanadyl remained unaffected. Aneuploidy effect in the D61M strain of Saccharomyces cerevisiae was induced by either V5 or V4, confirming that vanadium compounds are potentially antitubulin agents in eukaryotic cells. Although these compounds are very toxic in V79 cells, no mutagenic effect was observed in the presence or in the absence of S9 fraction.

Animals↗
PubMed1991

Metabolism of 5-methoxypsoralen by Saccharomyces cerevisiae.

Incubation of methoxypsoralen (5-MOP) in the presence of diploid yeast cells (Saccharomyces cerevisiae) before UV-A exposure leads to an incubation-time dependent decrease of photoinduced genotoxic effects. The reduction in photoinduced genotoxicity is stronger in cells grown in the presence of 20% glucose and containing high levels of cytochrome P-450 than in cells grown in the presence of 0.5% glucose and containing undetectable levels of cytochrome P-450. Inhibition of P-450 activity by specific inhibitors, such as tetrahydrofuran and metyrapone, strongly affects the observed decrease in 5-MOP genotoxicity, indicating the involvement of P-450 in 5-MOP metabolism. As demonstrated by spectrophotometric and chromatographic (HPLC) analysis during incubation of 5-MOP with P-450 containing yeast cells, 5-MOP gradually disappears from the cell supernatant of the incubation mixture. The reduction in the chromatographic peak corresponding to 5-MOP is accompanied by the appearance of a new peak that probably corresponds to a metabolite. As shown by the use of P-450 specific inhibitors, the metabolite appears to be due to P-450 mediated 5-MOP metabolisation. Its UV absorption spectrum suggests an alteration of the pyrone moiety of the 5-MOP molecule.

5-Methoxypsoralen↗
PubMed1990

Effects of acetone administration on drug-metabolizing enzymes in mice: presence of a high-affinity diethylnitrosamine de-ethylase.

Treatment of CD1 mice with acetone raised activities of hepatic microsomal p-nitrophenol hydroxylase, ethoxycoumarin de-ethylase, acetone hydroxylase and diethylnitrosamine de-ethylase (DENd) several-fold. P-450IIE1-linked acetone hydroxylase showed the highest inducibility. In microsomes from acetone-pretreated mice the cytochrome b5 and P-450 content was nearly doubled and their electrophoretic profile showed induction of a protein of Mr 53,000, probably P-450IIE1. Liver phase II enzymes were not affected by acetone treatment. Kinetic analyses of DENd were performed in control or acetone-induced microsomes and Km and Vmax were determined. Two distinctly apparent Km values (0.56 and 20.3 mM) were observed for DENd of control microsomes and at least 3 apparent Km values (0.05, 0.51, 8.4 mM) were observed in acetone-induced microsomes. Thus, acetone administration to mice induces a high-affinity form of DENd which can be important in vivo at low diethylnitrosamine (DEN) exposure as this enzyme functions when DEN concentration is below 0.1 mM.

Acetone↗
PubMed1989

High affinity diethylnitrosamine-deethylase in liver microsomes from acetone-induced rats.

The effects of acetone treatment on microsomal cytochrome P-450-dependent mono-oxygenases of the rat liver have been investigated to elucidate the role of this system in the metabolism of diethylnitrosamine (DEN). Acetone markedly enhanced the hepatic P-450 content and the activities of p-nitrophenol hydroxylase, acetone hydroxylase, ethoxycoumarin deethylase and DEN deethylase (DENd), whereas activities of pentoxy-resorufin O-deethylase and ethoxy-resorufin O-deethylase were not affected. Two distinct apparent Km values (0.43 and 9.1 mM), dependent on the substrate concentration, were observed for the DENd of acetone-induced microsomes. Only one Km value (8.4 mM) was observed for the DENd of control microsomes. In control microsomes at a DEN concentration of 1 mM, the N-deethylation of DEN was undetectable whereas in acetone-induced microsomes the N-deethylation rate was approximately 2.3 nmol/mg protein per min. The results suggest that acetone-induced microsomes of rat liver contain a high affinity form of DEN-deethylase which should be the P-450j isozyme (known to catalyze the oxidation of dimethylnitrosamine at low Km). P-450j is strongly enhanced by acetone treatment as indicated by the increase of the specific acetone hydroxylase. The treatment also enhanced the metabolism of DEN at substrate concentrations higher than 1 mM, suggesting that other P-450(s) catalyse DEN-deethylation although with lower substrate affinity. The low Km form of DENd is a P-450-dependent mono-oxygenase. It requires NADPH and O2, is inhibited by CO, but not by mannitol, superoxide dismutase, catalase or desferrioxamine. Its action therefore appears not to be mediated by oxygen radical species. Many solvents such as dimethylsulfoxide, dioxolane, chloroform and butanol when present at 10 mM in the incubation mixture inhibited the low Km form of DENd. However, pyrazole and piperonylbutoxide were found to be the strongest inhibitors. These results establish that acetone affects the metabolism of DEN, particularly at low concentrations, in a fashion somewhat similar to dimethylnitrosamine.

Acetone↗
PubMed1989

Psychotropic drug prescription in general practice in Italy: a two-week prevalence study.

A study on psychotropic drug monitoring was carried out in Verona over a 2-week period using information obtained during consultation with 3 GPs. Psychotropic drugs accounted for 23.4% and 24.3% of all prescriptions in men and women respectively. Benzodiazepines were the most frequently prescribed: 76% and 72% of all psychotropic prescriptions respectively in women and in men. No significant association between psychotropic drug prescription and age, sex, marital status and occupation was found in the present survey. In men only, those patients with higher educational level were more likely to receive a prescription for psychotropic drugs than those with a lower educational level. About 70% of men and 60.4% of women diagnosed by the GP as having a psychiatric problem were prescribed a psychotropic drug. However, the probability of a psychotropic being prescribed, when a psychiatric problem is identified by the GP, was significantly higher (p less than 0.05) in men than in women: odds ratio 39.37 and 16.33 respectively. Psychotropic drugs were prescribed in 35% of men and in about 48% of women in which a social problem was identified by the GP. Women were about 5 times more likely to receive a prescription than men: odds ratio 12 and 2.75 respectively. A significant influence of physical ill-health and educational level on psychotropic prescription emerged: both effects were independent of sex, psychiatric morbidity and social problems. Using a logistic regression analysis, an interactive effect between sex and conspicuous psychiatric morbidity and between sex and social problems was also found.

Adult↗
PubMed1988

Urban-rural differences in psychotropic drug prescribing in northern Italy.

Urban-rural differences in psychotropic drug prescribing were examined by comparing data from general practices in two contrasting areas of northern Italy. Patients attending the urban doctors were 1.5 times more likely to be prescribed a psychotropic drug than their rural counterparts. We also explored urban-rural differences in factors influencing psychotropic prescribing. Such influences were more numerous and complex in the urban than the rural setting.

Drug Prescriptions↗
PubMed1987

Psychiatric morbidity in an Italian general practice.

A two-stage screening strategy was applied in a single-handed general practice in northern Italy. The study was designed so that all the second-stage psychiatric interviews were conducted during the first phase of the study (group A patients), while self-report questionnaire (GHQ) and GP assessments only were collected during the second phase (group B patients). The estimated true case rate of psychiatric disorder (36%) did not differ between the two phases of the study, but there were marked differences in the general practitioner's diagnostic behaviour. During the first phase (when psychiatric interviews were being conducted in the practice), her behaviour was heavily biased towards diagnosing psychiatric disorder; 61% of the patients were regarded by her as psychiatric cases and the hidden psychiatric morbidity rate was only 9%. During the second phase of the study (no psychiatric interviews in the practice), only 37% of the patients were regarded as psychiatric cases by the GP, and the hidden morbidity rate was 59%. The results are interpreted as demonstrating that the presence of a psychiatrist conducting a two-stage screening survey in the practice had a profound effect on the diagnostic threshold. They also provide support for the use of the GHQ as a case-finding instrument in general practice.

Adult↗
PubMed1987

Psychotropic drug monitoring in general practice in Italy: a two-year study.

A psychotropic drug monitoring study in general practice was carried out in 1983 and 1984 using a computerized drug information system. The prescription data analysed in the study came from 68 general practitioners operating in south Verona and have been collected by 14 community pharmacies located in the same area. Benzodiazepine hypnotics were the most commonly prescribed drugs, followed by antidepressants and neuroleptics both in 1983 and in 1984. The distribution of the general practitioners in terms of low, medium and high prescribers was examined by analysing the rates of prescriptions per registered patient. The rates were obtained for the total number of prescriptions and also for each of the three different classes of psychotropic drug. The proportion of low and high prescribers decreased from 1983 to 1984 (18.3 versus 11.7 and 26.7 versus 16.7 for low and high prescribers respectively); this change was mainly due to the reduction in benzodiazepine prescriptions. No significant correlation was found between the rates of psychotropic drug prescriptions and list size. The monthly variation in prescription of the three drug classes followed a similar pattern during the two years; the fluctuations were clearly cyclical, more definitely in 1984 than in 1983 where the most relevant feature was the summer trough.

Adolescent↗
PubMed1986

Psychotropic drug use in Italy: national trends and regional differences.

Psychotropic drug sales data for Italy were examined for the years 1975-84. The principal findings were of more-or-less consistent annual increases in sales of antidepressants, minor tranquillizers and, to a lesser extent, of neuroleptics. These trends are interpreted in the context of the characteristics of the Italian National Health Service (NHS), and in relation to findings from psychotropic drug utilization studies in other Western countries. Regional differences in psychotropic drug sales for 1983/4 were also examined. Marked differences were found and, in general, levels of use were higher in North/Central Italy than in the South. Factors influencing regional differences were explored using regression analysis. Regional NHS expenditure (excluding that on drugs) was found to influence strongly the sales of all categories of psychotropic drug, whereas there was also a marked urban greater than rural difference in the sales of tranquillizers.

Antidepressive Agents↗