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T Giraldi

Publications and source records attributed to T Giraldi.

At least 37 records · Page 2Linked to original sources
PubMed1993

A non-invasive simple method for measurement of urinary excretion of melatonin in undisturbed mice.

Melatonin is a hormone involved in neuroendocrine responses; its plasma concentrations display a circadian pattern which is modified by stress. Studies for determining the effects of stressors on melatonin levels in laboratory animals present the difficulty that the procedures for blood sampling are by themselves potential stressors capable of influencing the levels of the hormone measured. A simple non-stressful method for measuring urinary excretion of melatonin has been consequently developed. The method is applicable to single undisturbed mice kept in conventional cages, and consists of urine collection on chromatographic paper followed by extraction and melatonin assay by radioimmunoassay. The use of this method with BD2F1 mice indicates nocturnal excretion of melatonin significantly higher than during the day; nighttime melatonin levels were shown to be suppressed by constant illumination. A significant increase in nocturnal melatonin excretion was caused by the application of rotational stress applied as a mild experimental stressor.

Animals↗
PubMed1991

[Regulation of platelet alpha2 adrenergic receptors in a population of patients with essential arterial hypertension and in normotensive subjects].

The development of specific binding techniques for the study of adrenergic receptors on circulating human blood cells has allowed a better understanding of the physiological alterations of adrenergic receptors and changes of adrenergic receptors in pathological conditions such as hypertension. Alpha adrenoceptors play an important part in blood pressure regulation at several sites. There are contradictory and conflicting reports on whether alpha receptor mechanisms are altered in essential hypertension. To address further the role of alpha 2 adrenoceptors in human essential hypertension the number and the affinity of alpha 2 adrenergic receptors and plasma catecholamine levels were measured in 20 normotensive and 24 hypertensive subjects. The median number of receptors (Bmax) was 159.10 +/- 14.38 fmol/mg protein for controls versus 179.09 +/- 13.26 fmol/mg protein for hypertensives. The median dissociation constant (KD) of the receptors for 3H-Yohimbine was 1.43 +/- 0.17 nmol/l for controls and 1.85 +/- 0.19 nmol/l for hypertensives patients. There were no differences in catecholamine plasma levels between the two groups. In controls platelet alpha 2 receptor number correlated with age (p less than 0.003) but not with blood pressure values. Our results show that measurement of platelet alpha 2 receptor levels and affinity is unable to differentiate a group of hypertensives from normotensives. Nevertheless, we cannot exclude a possible role of peripheral alpha 2 adrenergic receptors in the pathogenesis of high blood pressure.

Adult↗
PubMed1989

Effects of stress on tumor growth and metastasis in mice bearing Lewis lung carcinoma.

The progression of Lewis lung carcinoma has been examined in mice under the stress of different housing and experimental conditions. The maintenance of the animals in a low stress environment decreased the weight of spontaneous lung metastases in comparison with conventional housing. The handling of mice in the low stress environment for intraperitoneal saline administration increased metastasis formation, whereas the application of a psychological stressor (spatial disorientation) to these animals increased both primary tumor growth and metastasis formation. These results indicate that psychological and experimental stressors can modulate, presumably via neuroendocrine mechanisms, the host's antitumor responses which can control metastases and primary tumor independently from each other.

Animals↗
PubMed1988

Platelet alpha 2-adrenoceptor modifications induced by long-term treatment with indapamide in essential hypertension.

The effect of long-term treatment with indapamide in platelet alpha 2-adrenoceptors has been evaluated in 10 patients with essential hypertension, in a double-blind, cross-over study with placebo. After three months of therapy, indapamide significantly reduced mean blood pressure (from 137 +/- 12 to 116 +/- 6 mm Hg, p less than 0.001), whereas heart rate did not change (from 72 +/- 8 to 73 +/- 7 beats/minute). At the same time, platelet alpha 2-adrenoceptor number increased (from 168.2 +/- 48.4 to 256.8 +/- 14.5 fmol/mg protein, p less than 0.02), whereas the dissociation constant did not change (from 3.79 +/- 2.9 to 4.97 +/- 4.48). The plasma norepinephrine level was significantly reduced after long-term treatment with indapamide (from 275 +/- 118 to 210 +/- 56 pg/ml, p less than 0.02). These results bring about an inhibition of norepinephrine release from sympathetic nerve endings with a likely secondary increase of the number of platelet alpha 2-adrenoceptors.

Adult↗
PubMed1988

Effects of an inducer and an inhibitor of hepatic metabolism on the antitumor action of dimethyltriazenes.

To investigate the role of monomethyltriazenes as the active metabolites of antitumor dimethyltriazenes, the in vivo simultaneous treatment with an inducer (phenobarbital, PB) or an inhibitor (carbon tetrachloride, CCl4) of hepatic drug metabolism was examined in mice bearing Lewis lung carcinoma. Treatment with PB or CCl4 with the dosage and schedules employed proved to be effective in markedly modifying the N-demethylation of the three dimethyltriazenes tested, as had been determined in vitro. No unambiguous increase by PB, or decrease by CCl4, which might theoretically be expected if metabolic conversion to monomethyltriazenes was involved, was observed for the antitumor and antimetastatic activity of dimethyltriazenes. At the same time, a difference was noted between the effects on primary tumors and those on metastases. These data support the view that generalizations on the relevance of monomethyltriazenes as the active metabolites responsible for the antitumor and antimetastatic activity of dimethyltriazenes may not be valid.

Animals↗
PubMed1987

Morphological analysis of metastatic potential and antimetastatic drug effects in mice bearing two lines of Lewis lung carcinoma.

Two lines of Lewis lung carcinoma with a different potential to metastasize spontaneously to the lungs have been examined for their cytological and histological characteristics. Metastatic potential appears to be related with parenchymal organization of the primary tumours, since large haemorrhagic areas containing detached tumour cells and the absence of endothelialized capillaries are observed only in the line with high metastatic potential. At the same time, the cytological characteristics of the cells of the two tumour lines are similar, and do not seem to be related with metastatic potential. After treatment with the selective antimetastatic drugs ICRF-159 and DM-COOK, and with DTIC, the histological appearance of the line with high metastatic potential becomes similar to that of the line with low metastatic potential. These data seem to indicate that the early phases of tumour spread occurring in the primary tumour are of relevance for metastatic potential and control by antimetastatic drugs, and suggest that for DTIC such antimetastatic action may participate to its clinical antitumour effects.

Animals↗
PubMed1986

Antihypertensive activity of arylidenaminoguanidine derivatives.

The synthesis of new benzylidenaminoguanidine compounds is described. Some of these compounds were tested for antihypertensive activity in conscious unrestrained spontaneously hypertensive rats. The compounds examined possess a significant antihypertensive activity, qualitatively different from that of clonidine. For the tested compounds, the absence of the transient rise in blood pressure, which appears immediately after administration of clonidine-like drugs, is noteworthy.

Animals↗
PubMed1985

Inhibition of cell-surface neutral protease of Ehrlich ascites tumor cells by potassium p-(3,3-dimethyl-1-triazeno) benzoate.

Ehrlich ascites tumour (EAT) cells possess a trypsin-like neutral protease on the cell surface. The antimetastatic triazene drug potassium p-(3,3-dimethyl-1-triazeno) benzoate (DM-COOK) inhibits this neutral protease, and also trypsin. Incubation of EAT cells with human erythrocytes (ratio of 1 to 5) at 37 degrees C for 18 h caused haemolysis of 28.8% of the erythrocytes. Addition of millimolar concentrations of DM-COOK to a fixed quantity (2.5 X 10(8)) of EAT cells caused a dose-related inhibition of haemolysis. DM-COOK was strongly bound to EAT cells and could not be removed by repeated washing.

Aminopeptidases↗
PubMed1985

Tumor cell metastasis and surface neutral proteinase: effects of antimetastatic and antitumor drugs.

The levels of a trypsin-like neutral proteinase present on tumor cell surface (SNP) have been determined in P388, L1210, TLX5 leukemias, and in two lines of Lewis lung carcinoma having different metastatic potential. No correlation between metastatic potential and SNP levels of the tumor lines examined has been observed, and metastasis depression by antimetastatic and antineoplastic drugs was not accompanied by SNP inhibition. These data seem to support the view that metastatic potential is not necessarily related to tumor proteinase levels.

Animals↗
PubMed1984

Infiltration of liver and brain by tumor cells in leukemic mice: prevention by dimethyltriazenes and cyclophosphamide.

The dimethyltriazenes p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) increase, unlike cyclophosphamide (Cy), the survival time of mice bearing L1210 lymphoid leukemia, P388 lymphocytic leukemia and TLX5 lymphoma with a mechanism unrelated to cytotoxicity for tumor cells. The in vivo bioassays of brains, and the histologic examinations of the livers of leukemic mice show that DM-COOK and DTIC prevent leukemic infiltration in these organs at dosages devoid of cytotoxic effects for peritoneal tumor cells. At a dosage equitoxic with that of dimethyltriazenes, cyclophosphamide causes the absence of tumor cells in the peritoneal cavity and in the brains and livers of mice bearing P388 and L1210 leukemias. DM-COOK and DTIC thus possess a mild or insignificant cytotoxic action together with antimetastatic properties also on mouse transplantable leukemias. The use of DM-COOK appears advantageous over that of cyclophosphamide and DTIC because of a reduced host toxicity, which is particularly evident for cyclophosphamide and DTIC on liver parenchyma and bone marrow.

Animals↗
PubMed1984

Hemostasis and mechanism of action of selective antimetastatic drugs in mice bearing Lewis lung carcinoma.

The selective antimetastatic agents p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and (+/-)1,2-di(3,5-dioxopiperazin-1-yl)propane (ICRF-159) have been shown to markedly depress the formation of spontaneous hematogenous metastases in mice bearing s.c. Lewis lung carcinoma, with a mechanism unrelated to cytotoxicity for tumor cells. The effects on hemostasis of DM-COOK, DTIC and ICRF-159 have thus been examined in comparison with those of a purely cytotoxic agent, cyclophosphamide, in mice bearing i.m. Lewis lung carcinoma. The parameters considered are the number of platelets and their aggregability, prothrombin and partial thromboplastin times, plasma fibrinogen concentration and tumor cell procoagulant activity. Slight variations are caused by drug treatment in tumor-bearing mice as compared with untreated tumor-bearing controls; the pattern of effects of the selective antimetastatic agents does not differ from that of the reference cytotoxic compound used, cyclophosphamide. These data thus indicate that the effects on hemostasis of the drugs examined can contribute only marginally to their antimetastatic action, since more pronounced effects on hemostasis have been shown to be required to significantly affect metastasis formation.

Animals↗
PubMed1984

Antineoplastic activity and toxicity of an organometallic complex of ruthenium(II) in comparison with cis-PDD in mice bearing solid malignant neoplasms.

The antineoplastic activity of an organometallic complex of ruthenium(II), [cis-RuCl2(DMSO)4]o, has been examined in comparison with that of cis-PDD, using three metastasizing tumors of the mouse: Lewis lung carcinoma, B16 melanoma and MCa mammary carcinoma. [cis-RuCl2(DMSO)4]o significantly reduces primary tumor growth in all the tumors tested, and its activity is similarly pronounced at three different dosages in mice bearing Lewis lung carcinoma. On the contrary, the survival time of animals having i.v. or i.m. tumor implants are only moderately increased, and also in the case of combined treatments with surgery. The antineoplastic activity of cis-PDD appears to be less pronounced than that of [cis-RuCl2(DMSO)4]o, and is limited to mice bearing B16 melanoma, which, among the three tumors used, appears to be naturally more responsive to cis-PDD and [cis-RuCl2(DMSO)4]o. The use of [cis-RuCl2(DMSO)4]o appears advantageous over that of cis-PDD since, unlike cis-PDD, its antineoplastic effects have been obtained at dosages with reduced host toxicity, indicated by the absence of significant hematological toxicity and toxicity for normal proliferating tissues.

Animals↗
PubMed1984

Effects of antimetastatic dimethyltriazenes in mice bearing Lewis lung carcinoma lines with different metastatic potential.

The effects of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and its benzenoid analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) have been examined in mice bearing two Lewis lung carcinoma lines with different potential to spontaneously metastasize to the lungs. DTIC similarly depresses the growth of intramuscular and pulmonary tumor nodules, and also reduces the development of spontaneous lung metastases for both tumor lines. DM-COOK causes effects similar to those of DTIC on the tumor line with low metastatic potential; on the contrary, although it is highly active in inhibiting lung metastasis formation for the line with high metastatic potential, it is ineffective or marginally cytotoxic on intramuscular or on pulmonary tumor nodules, respectively. These data indicate, at least for the dimethyltriazene DM-COOK, a dissociation between sensitivity to cytotoxic and antimetastatic effects, and that tumor cell populations with a higher potential to spontaneously metastasize have a greater sensitivity to selective antimetastatic effects, concomitant with a reduced cytotoxic response to the effects of this drug.

Animals↗