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R Cozzi

Publications and source records attributed to R Cozzi.

66 records · Page 4Linked to original sources

Aberrations induced in chromosomes of somatic cells of Drosophila melanogaster irradiated in C-metaphase.

Experiments conducted on the X irradiation of neural ganglia of Drosophila melanogaster are described. The ganglia were placed in saline containing colchicine. After two hours, they were irradiated and then samples were fixed at 5,15,25,35 minutes from the beginning of irradiation. The results obtained show that the aberration level increases with time subsequent to fixing. This increase takes place first for chromatid deletions and then for isochromatid deletions and chromatid exchanges. Gaps and subchromatid exchanges do not, on the contrary, show any increase with time. We did not observe a difference in radiosensitivity between the sexes. Some hypotheses are put forth in an attempt to explain these results.

Animals↗

Cytological analysis of X-ray-induced aberrations in spermatocytes I and the somatic ganglia of male Drosophila melanogaster.

The correlation between damage induced in somatic cells and that induced in germinal cells of the same genetic pool of individuals is important in establishing the possibility of extrapolation of this damage to the offspring. We have used Drosophila melanogaster to compare cytologically the frequency of aberrations induced in the cells of somatic ganglia and in the spermatocytes I of males irradiated with 625 R X-rays. The spermatocytes were more sensitive than the gangliar cells to radiation: the aberrations induced in the spermatocytes I were three times more frequent than those induced in the ganglia. The distribution of the aberrations was, however, similar. The most important variable element lies in our observing no symmetrical exchanges in the spermatocytes. This result seems to us to be related to the fact that in the males of D. melanogaster there is no crossing-over.

Animals↗

Evidence for a dopaminergic activity of methysergide in humans.

The acute administration of 2 mg of methysergide significantly reduced plasma prolactin levels in nine normal subjects and in seven hyperprolactinaemic patients. The prolactin lowering effect of this drug was abolished by sulpiride. Morever methysergide lowered plasma GH levels in four out of nine acromegalic patients, who were also responsive to a dopaminergic drug such as bromocriptine. Although methysergide did not significantly blunt the TRH-induced prolactin release, our data suggest that this drug may affect GH and prolactin release through a dopaminergic mechanism of action. This effect should be taken into account when methysergide is employed as antiserotoninergic drug in neuroendocrinological studies.

Acromegaly↗

Effectiveness of the dopamine agonist lisuride in the treatment of acromegaly and pathological hyperprolactinemic states.

We have studied the effects of the chronic administration of the dopamine agonist lisuride (L) in 21 acromegalics (group 1) and in 25 patients with pathological hyperprolactinemia (group 2). Before starting the treatment levels of PRL and/or GH were determined during acute tests with L (0.3 mg po) or TRH (0.2 mg iv). L was given in doses ranging between 0.4 and 2.4 mg/day. GH and/or PRL were determined at monthly intervals, TRH (6 patients of group 1 and 10 of group 2) was repeated during L therapy. In 10 patients of group 1 GH levels were reduced below 10 ng/ml by L therapy; in the remaining patients GH levels were reduced by 50% of the pretreatment values or they were unchanged. The correlation (p less than 0.01) found between GH levels during acute and chronic L administration indicates that GH changes after acute test are predictive of the outcome of the treatment. In all patients PRL was reduced during the therapy to at least 50% of the basal values and in most patients PRL fell to the normal range. No correlation was found between PRL levels during acute and chronic L administration. During the therapy TRH still increased GH levels in most patients whereas it failed to raise PRL. The withdrawal of L was followed by a rapid return of GH to the pretreatment values whereas PRL showed a slower increase. In acromegalics whose GH was lowered by L there was also a marked amelioration of clinical and metabolic parameters. The lowering of PRL was accompanied by the resumption of ovulatory menses even in patients with tumoral hyperprolactinemia. Males reported improvement in sexual performance. An improvement of visual field occurred in 1 patient. In 1 patient with a large prolactinoma serial computerized tomography scans performed during 2 yr of treatment showed a marked reduction of the tumor size.

Acromegaly↗

Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay.

Oxidative stress due to oxygen and various radical species is associated with the induction of DNA single- and double-strand breaks and is considered to be a first step in several human degenerative diseases, cancer and ageing. Naturally occurring antioxidants are being extensively analysed for their ability to protect DNA against such injury. We studied three naturally occuring compounds, Ascorbic Acid, Melatonin and Ellagic acid, for their ability to modulate DNA damage produced by two strong radical oxygen inducers (H2O2 and Bleomycin) in cultured CHO cells. The alkaline Comet assay was used to measure DNA damage and a cytofluorimetric analysis was performed to reveal the intracellular oxidative species. The data showed a marked reduction of H2O2- and Bleomycin-induced DNA damage exerted by Ellagic Acid. On the contrary Ascorbic acid and Melatonin appeared to induce a slight increase in DNA damage per se. In combined treatments, they caused a slight reduction of H2O2-induced damage, but they did not efficiently modulate the Bleomycin-induced one. The Dichlorofluorescein diacetate (DCFH-DA) cytofluorimetric test confirmed the strong scavenging action exerted by Ellagic Acid.

Animals↗

[Medical treatment of acromegaly with dopaminergic agents].

The medical treatment of acromegaly with dopaminergic drugs has its physiopathological premise in the observation that agents capable of stimulating dopaminergic receptors directly are capable of determining GH secretion inhibition in a large percentage of acromegalic patients. Chronic administration of 5-20 mg/die of bromocryptin, long acting dopaminergic agonist, leads to a stable reduction in the levels of GH and somatomedin C (SmC) in about 50% of patients. However, these are only normalised in 20%. Treatment induces marked improvement in the clinical and metabolic changes typical of acromegalic disease. The therapeutic effect of dopaminergics may be maintained for periods of treatment lasting years but upon suspension of treatment pH levels return quickly to pretreatment levels. The antitumoral effect of the dopaminergic frequently encountered in prolactinomas is a rarer event in acromegaly and occurs more readily in patients with mixed secreting GH and PRL tumours than in pure GH. Currently octractide, a long lasting somatostatin analogue, is the most effective drug in the medical treatment of acromegaly; however the dopaminergic agonists remain a valid alternative.

Acromegaly↗

Influence of spermidine on sister chromatid exchanges induced by alkylating agents in mammalian cells in vitro.

Sister chromatid exchanges (SCEs) are a very sensitive genetic end-point for in vitro identification of presumed carcinogenic and mutagenic agents, although the mechanism of their formation is still to be elucidated. The present work shows the influence of spermidine on SCE induction by two different DNA damaging agents: Mitomycin-C (MMC) and N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG). The SCE level induced by MMC was significantly decreased by spermidine. On the contrary, MNNG-induced SCEs were not affected. It has recently been suggested that MMC, via its reduced metabolite mitosene, produces bulky mono-and bi-adducts in DNA, mainly located in the minor groove of the double helix. MNNG, instead, directly methylates several electrophilic sites of DNA bases, such as the N7 and the O6 of guanines and the N3 of adenines. Both MMC and MNNG, despite their different mechanism of action, are potent SCE inducers. Spermidine, similarly to its structural analogue Spermine, is known to interact with DNA phosphate groups and to bind reversibly to the minor groove, thus stabilizing the double helix structure. Spermidine, being therefore ineffective on the MNNG-mediated DNA methylation, might affect DNA, making it structurally unavailable for MMC binding.

Animals↗

Reduction of adriamycin cardiotoxicity by enoximone.

Several non catecholamine, non glycoside cardiotonic drugs have been described recently. New compounds include amrinone, sulmazole, milrinone and pimobendan. In an attempt to alleviate or prevent anthracycline toxicity, we have reported that these compounds reduce the negative effects of adriamycin, 4-epiadriamycin and esorubicin in isolated guinea pig atria. The present study reports the effects of a new cardiotonic agent: enoximone. Enoximone was administered after adriamycin (100 micrograms/ml) on the isolated and spontaneously beating atria, and on electrically driven left atria of guinea pig-in normodynamic and hypodynamic conditions. Exposure for 60 minutes to the antitumor drug causes a depression of contractile force (g) and its derivative versus time (dF/dt, as maximal rate of contractile force). The negative effects of adriamycin are antagonised by enoximone (100, 200 micrograms/ml).

Animals↗