PubMed Health⌕ Search

Biomedical subjects

T Facchinetti

Publications and source records attributed to T Facchinetti.

18 recordsLinked to original sources
PubMed1991

Triiodothyronine control of ATP-citrate lyase and malic enzyme during differentiation of a murine preadipocyte cell line.

In the Ob 17 preadipocyte cell line, during adipose differentiation, T3 amplified the progressive expression of two enzymes of the lipogenic pathway, ATP-citrate lyase (ATP-CL) and malic enzyme (ME) as previously described for fatty acid synthase (FAS) and fatty acid synthesis, and in the same time-period of development. However, the stimulation by T3 was sustained at late stages of differentiation whereas it declined in FAS studies. The stimulation was preceded by an increase in the relative abundance of the specific mRNAs. Two ME mRNA species were detected (21S and 27S) and found to be differently distributed. Their abundance was asynchronously increased by T3 with a predominant effect on the 21S species. Culture of the cells in a thyroid-hormone depleted medium prevented any significant increase of ME activity. Early inclusion of T3 largely restored ME development whereas late elimination of T3 only moderately impaired it. It is suggested that T3 plays a crucial role at an early step of adipose differentiation, this leading to an increased expression of a set of late adipose phenotypes such as several lipogenic enzymes.

ATP Citrate (pro-S)-Lyase↗
PubMed1986

In vitro studies on anthracycline haloderivatives.

A new class of anthracycline derivatives carrying a halogen atom in the 4' position of the aminosugar moiety was tested in cytotoxicity studies on HeLa cells and on P388 cell lines sensitive and resistant (P388/DX) to doxorubicin, in comparison with the parent drugs doxorubicin (DX) and daunorubicin (DNR). 4'-Haloderivatives of DX generally appear to be more cytotoxic than DX on HeLa, P388 and P388/DX cells. Cellular kinetic studies of DX-haloderivatives on HeLa, P388 and P388/DX cell lines show that they accumulate inside the cell in higher amounts than DX, whereas DNR haloderivatives accumulate in HeLa and P388 cells at levels similar to DNR; only in P388/DX is their accumulation higher as compared with DNR. The results reported suggest that, besides drug accumulation, other factors are involved in the cytotoxic mechanism of action of this class of compounds. Therefore 4'-haloderivatives represent a class of compounds with promising activity, in particular regarding anthracycline-resistant cell lines.

Animals↗
PubMed1985

Doxorubicin induces calcium release from terminal cisternae of skeletal muscle. A study on isolated sarcoplasmic reticulum and chemically skinned fibers.

In this study, we investigated the effect of the anticancer drug doxorubicin on Ca2+ fluxes of isolated highly purified sarcoplasmic reticulum fractions (longitudinal tubules and terminal cisternae (Saito, A., Seiler, S., Chu, A., and Fleischer, S. (1984) J. Cell Biol. 99, 875-885] and of chemically skinned skeletal muscle fibers of the rabbit. In terminal cisternae, doxorubicin inhibits Ca2+ uptake (IC50 at 0.5 microM) and increases 2.6-fold Ca2+-dependent ATPase rate (half-maximal activation at 3 microM) and unidirectional Ca2+ efflux (8-fold stimulation at 25 microM). On the contrary, doxorubicin is without effect on longitudinal tubules. In skinned muscle fibers, doxorubicin induces rapid and transient Ca2+ release, as measured by tension development (half-maximal stimulation at 6 microM), which is completely and reversibly inhibited by ruthenium red, a known inhibitor of Ca2+ release from isolated terminal cisternae. Doxorubicin has no effect on the sarcoplasmic reticulum Ca2+ pump and on the contractile apparatus of skinned muscle fibers. It is concluded that doxorubicin activates Ca2+ release from sarcoplasmic reticulum and opens a Ca2+ efflux pathway (Ca2+ channel) selectively localized in terminal cisternae. Doxorubicin might interact with Ca2+ channels involved in physiological Ca2+ release.

Animals↗
PubMed1983

The influence of selenium intake on chronic adriamycin toxicity and lipid peroxidation in rats.

This paper reports on the influence of selenium intake on antioxidant protective systems during chronic adriamycin (AM) treatment in rats. Rats were kept for 14 weeks on a selenium deficient (Se-) diet or a diet containing selenium (Se+). No significant differences were found in any group with regard to the cardiac content of total and reduced glutathione (GSH) and heart superoxide dismutase specific activity. AM treatment did not modify lipid peroxidation as measured by cardiac malondialdehyde (MDH) formation in rats receiving either the Se- or the Se+ diet. In the Se+ rats AM had no effect on the exhalation of ethane or pentane but decreased the exhalation of ethane and increased that of pentane in the SE- rats. In Se- AM-treated rats mortality was higher. Since this did not seem to be correlated with modifications of any of the biochemical parameters taken into consideration, it is suggested that the better resistance of Se+ animals to AM treatment is related to some factors not yet identified.

Animals↗
PubMed1982

Further studies on adriamycin induced in vitro lipid peroxidation.

Adriamycin (AM)-induced lipid peroxidation was studied in rat liver microsomal system, measuring colour produced by thiobarbituric acid (TBA) reactive material and the development of volatile hydrocarbons. The onset of this degradative process is closely related to the AM content. This phenomenon appears to be highly influenced by the buffer used for the microsomal preparation. The effect of AM on FE--ADP-induced lipid peroxidation in liver microsomes has also been studied.

Adenosine Diphosphate↗
PubMed1979

Pharmacokinetics of cyclophosphamide after prolonged low dose treatment in ovarian cancer patients.

We have studied Cyclophosphamide (Cy) pharmacokinetics in 9 patients after their first intravenous dose of 100 mg, and in 9 patients after 6--13 months of continual treatment with the same dose every day. The half-life of Cy was shorter (p less than 0.05) in the latter group, the Co was greater (less than 0.01) and the Vd was clearly less (p less than 0.01). The AUC was unchanged.

Cyclophosphamide↗
PubMed1978

A differential interaction of daunomycin, adriamycin and their derivatives with human erythrocytes and phospholipid bilayers.

Drug-membrane association of daunomycin, adriamycin and three of its derivatives, adriamycin-14-octanoate (AD-14-OCTA), adriamycin-14-acetate (AD-14-ACE) and N-trifluoroacetyladriamycin-14-valerate (AD32), was studied using phospholipid bilayers and human erythrocytes. The various drugs exhibited a differential affinity to membrane-lipid domains. Lipid-incorporated drugs exhibit a marked change in the shape of the emission spectrum which was utilized for the evaluation of the apparent dielectric constant, epsilon, of the environment surrounding the anthracycline moiety, as well as for the determination ofthe partitioning constant. By measuring the fluorescence polarization and the fluorescence lifetime of the incorporated drugs, rotational relaxation times of 4--8 ns were derived. These parameters provide a supportive evidence of the association of the fluorophore of the drugs with membrane-lipid domains. The anthracycline derivatives interact to a different degree with dipalmitoyl phosphatidylcholine and phosphatidylserine as reflected by changes in their thermotropic properties assessed by differential scanning calorimetry. Daunomycin was the most effective in decreasing the temperature of the phase transition and brought about a comparable reduction in the enthalpy of melting as AD32 and AD-14-OCTA. Adariamycin was the least potent of the series. AD-14-ACE and AD32 protected erythrocytes against hypotonic lysis, adriamycin and daunomycin had no significant effect on the susceptibility to hypotonic lysis, whereas AD-14-OCTA proved to be hemolytic even at low concentration (approx. 10(-7M).

Calorimetry, Differential Scanning↗
PubMed1978

Intercalation with DNA is a prerequisite for daunomycin, adriamycin and its congeners in inhibiting DNAase I.

DNAase I from bovine pancreas is inhibited by Daunomycin, Adriamycin, Adriamycin-14-acetate and Adriamycin-14-octanoate, whereas it is not inhibited by N-trifluoroacetyladriamycin-14-valerate or N-trifluoroacetyl-adriamycin. The present study suggests that these inhibitors act not directly on the enzyme, but on DNA, forming stable complexes and thus interfering with enzyme activity. The correlation between DNA binding and enzyme inhibition is demonstrated by the fact that the compounds forming complexes with DNA inhibit DNAase I activity, whereas those which do not form complexes with DNA cause no inhibition.

DNA↗
PubMed1978

A differential interaction of daunomycin, adriamycin, and N-trifluoroacetyladriamycin 14-valerate with mouse peritoneal macrophages.

The interaction of three anthracycline drugs, daunomycin, Adriamycin, and N-trifluoroacetyladriamycin 14-valerate, with mouse peritoneal macrophages was explored. As assessed by drug-specific cytofluorescence, Adriamycin and daunomycin accumulated slowly within macrophages, first staining the nucleus and then the cytoplasmic inclusions that were induced by the drug treatment. N-Trifluoroacetyladriamycin 14-valerate distributed rapidly into the cells, was excluded from the nucleus, and induced numerous cytoplasmic inclusions. Electron microscopy revealed that the cytoplasmic inclusions were vacuoles containing some amorphous material and not the classical autophagic vacuoles containing organelles and membrane lamellae. All the drugs induced cell shrinkage with time and brought about cell death within 24 hr. Loss of cell function and viability was dose and time dependent; i.e., a 6-hr incubation with daunomycin or Adriamycin, 2.5 microgram/ml, brought about a 50% reduction in the phagocytic capacity of the treated macrophages. The damaging potency towards macrophages (daunomycin greater than Adriamycin greater than N-trifluoroacetyladriamycin 14-valerate) is in the reverse order to the in vivo therapeutic efficiency.

Animals↗
PubMed1977

Hydroxylation of three benzodiazepines in vitro.

Three structurally related benzodiazepines were studied as substrates for hydroxylation by liver microsomal enzymes of rats and mice. The Vmax was comparable for dechlorodesmethyldiazepam, desmethyldiazepam, and 2'-chlorodesmethyldiazepam in the two animal species. The apparent Km decreased from dechlorodesmethyldiazepam to 2'-chlorodesmethyldiazepam for liver microsomal enzymes from both animal species. The hydroxylation of desmethyldiazepam and 2'-chlorodesmethyldiazepam yielded two pharmacologically active metabolites, oxazepam and lorazepam, respectively.

Animals↗
PubMed1977

The metabolism and antitumour activity of the enantiomers of cis- and trans-4-methylcyclophosphamide.

4-Methylcyclophosphamide, an analogue of the antitumour agent cyclophosphamide, exists in cis and trans forms, each of which comprises a pair of optical isomers. The extents of metabolism by rat liver microsomes during 20 min were compared for the four steroisomers incubated separately, and for the racemic cis and trans-derivatives in admixture, using mass spectrometry and gas chromatography respectively. In comparative antitumour tests against the ADJ/PC6 plasma cell tumour in mice, the racemic cis and trans forms of 4- and 6-methylcyclophosphamide had similar therapeutic indices. The four stereoisomers of 4-methylcyclophosphamide exhibited an approx. two-fold range in therapeutic index so that there was no marked effect on either metabolism or antitumour activity occasioned by change of configuration either at C-4 or at phosphorus.

Animals↗