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B Barbieri

Publications and source records attributed to B Barbieri.

At least 37 records · Page 2Linked to original sources
PubMed1987

Chemical and biological characterization of 4'-iodo-4'-deoxydoxorubicin.

4'-Iodo-4'-deoxydoxorubicin is a doxorubicin (DXR) analogue with greater lipophilicity and reduced basicity of the amino group. In vitro 4'-iodo-4'-deoxydoxorubicin is more cytotoxic than DXR against a panel of human and murine cell lines and is characterized by a higher and faster uptake. In vivo, the spectrum of activity of 4'-iodo-4'-deoxydoxorubicin is comparable to that of DXR, but the new compound has higher activity against murine P388 leukemia resistant to DXR and against pulmonary metastases from Lewis lung carcinoma. Moreover, the new analogue exhibits antitumor activity also after p.o. administration and shows no cardiotoxicity in experimental systems.

Administration, Oral↗
PubMed1986

Biochemical and biological activity of the anthracycline analog, 4-demethyl-6-O-methyl-doxorubicin.

The chromophore-modified derivative of doxorubicin, 4-demethyl-6-O-methyl-doxorubicin, has been tested for antitumor activity in a range of experimental murine tumor systems. In contrast to the inactive 6-O-methyl derivative of daunorubicin, 4-demethyl-6-O-methyl-doxorubicin provided antitumor effects comparable to that of the parent compound. In addition, detailed DNA-interaction studies showed that the doxorubicin derivative retains the ability to bind DNA by the intercalation mechanism. However, the binding affinity was appreciably reduced following structural modification in the anthraquinone chromophore. On the basis of the proposed models of intercalation, these results could be rationalized in terms of steric influence of the bulky methoxy group. The results of this study are in agreement with the correlation already observed between DNA binding and relative antitumor activity of anthracyclines.

Animals↗
PubMed1986

Antitumor and toxicity evaluation of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.

The antitumor activity of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in P388 ascitic leukemia, disseminated Gross leukemia, and advanced mammary carcinoma. In P388 leukemia, free drug and drug entrapped in liposomes demonstrated equivalent antitumor activity at doses of 2.2 and 4.4 mg/kg, demonstrating 52% and 69% ILS (increase in life-span), respectively. Free doxorubicin at a dose of 10 mg/kg was superior, producing a 185% ILS against 82% with liposomal doxorubicin. With an increase in administered dose the antitumor response with liposomal doxorubicin was much more pronounced; at doses of 20 and 25 mg/kg the ILS was in excess of 376%, with five of ten mice surviving tumor-free. In Gross leukemia, the optimum dose of free doxorubicin, 10 mg/kg, brought about 186% T/C (median survival in treated mice over that in controls, X 100), whereas with liposomal doxorubicin the optimum dose was 16.9 mg/kg, which yielded 214% T/C. In advanced mammary carcinoma, the maximum tumor regression with free doxorubicin was at a dose of 7.5 mg/kg, with two of six mice dying of toxicity. Liposomal doxorubicin caused maximum tumor regression at 10.8 mg/kg dose with no toxic deaths. Doxorubicin entrapped in cardiolipin liposomes was much less toxic than free drug at high doses in normal mice.

AKR murine leukemia virus↗
PubMed1984

Interactions of purified rat factor VIII/von Willebrand factor with rat and human platelets--effect of albumin and ristocetin.

Rat platelets do not respond to ristocetin in their own plasma nor do they aggregate in the presence of bovine or porcine factor VIII von Willebrand factor (F VIII R:WF) or human F VIII R:WF in presence of ristocetin. However, rat plasma supports ristocetin induced aggregation of washed human platelets. In this study we report on purification of rat F VIII R:WF from cryoprecipitate. Similarly to porcine or bovine material, purified rat F VIII R:WF induced aggregation of human washed fixed platelets. This effect was enhanced by addition of ristocetin and was not modified by addition of albumin. Rat washed platelets were aggregated by ristocetin in the presence of rat or human F VIII R:WF provided that high concentrations of ristocetin are added in a system essentially free of extraneous proteins. Increasing concentrations of albumin dramatically reduced the ability of ristocetin to aggregate rat platelets while human platelet aggregation by human or rat F VIII R:WF was only moderately affected. These studies show that rat F VIII R:WF can interact with rat and human platelets. The lack of response of rat platelets to ristocetin in their own plasma is most likely due to a low sensitivity of rat platelets to this drug and to an inhibitory activity of plasma proteins on this reaction.

Animals↗
PubMed1983

Prostacyclin production by human endothelial and bovine smooth muscle cells in culture. Effect of repeated stimulation with arachidonic acid, thrombin and ionophore A23187.

Prostacyclin (prostaglandin I2) is the major product of arachidonic acid metabolism in vascular cells. Its physiological role may be linked to the ability of the cells to respond continuously with prostaglandin I2 production to a variety of stimuli. We report that human endothelial cells or bovine smooth muscle cells in culture respond with prostaglandin I2 synthesis to a first but not to a second stimulation with arachidonic acid. The development of this refractoriness was independent of the arachidonic acid concentration used (6.6-25 microM) and lasted for about 6 h. The same time was required for the cells to recover completely after inhibition of cyclooxygenase activity by aspirin. Neither cis-polyunsaturated fatty acids (linoleic or oleic acids) nor stearic acid (a long-chain saturated fatty acid) prevented the generation of prostaglandin I2 by arachidonic acid. Similarly to arachidonic acid, thrombin and ionophore A23187 could elicit vascular prostaglandin I2 synthesis only once. Pretreatment of the cells with arachidonic acid rendered the cells unresponsive to any other stimulus. These results indicate that the mechanism of the refractoriness induced by arachidonic acid was different from that induced by the other stimuli. It is proposed that vascular cells cannot be stimulated continuously to produce prostaglandin I2, but this process is regulated by different feedback mechanisms.

Animals↗
PubMed1981

Effects of any epoxymethano stable analogue of prostaglandin endoperoxides (U-46619) on human platelets.

U-46619 is a stable epoxymethano analogue of cyclic endoperoxide PGH2. We studied platelet aggregation, 14C-5HT release, LDH extrusion and prostaglandin and thromboxane production induced by this compound in platelet-rich plasma samples from 15 healthy volunteers. Each subject was tested both before and 90 min after aspirin (500 mg) ingestion. The threshold aggregating concentration (TAC) of U-44619 ranged between 0.18 and 0.90 micro M. Aggregation was maximal between 40 and 60 min after venipuncture and was concentration-dependent. At concentrations below the TAC, U-44619 induced primary reversible aggregation with minimal 14C-5HT release. At TAC or higher concentrations aggregation and release proceeded as parallel events. Neither prostaglandin or thromboxane production nor LDH loss could be detected in any of the situations tested. Aspirin ingestion did not modify the pattern of platelet responses. In unstirred, not aggregated platelet samples 14C-5HT release by U-46619 occurred to a similar extent as in stirred, aggregated platelet samples. Addition to citrated PRP of 0.3 mM Na2 EDTA blocked both aggregation and release induced by U-46619. This compound, however, aggregated washed platelets resuspended in Ca++-free-tyrode-albumin containing fibrinogen. The mechanism by which U-46619 activates platelets differs from that of all other common aggregating agents.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1980

Impaired thromboxane production by newly formed platelets after aspirin administration to thrombocytopenic rats.

The in vivo inhibitory effect of aspirin on platelet cyclo-oxygenase is irreversible and lasts for the entire platelet life-span. Reappearance of cyclo-oxygenase activity in blood after aspirin has been proposed as a measure of the formation of new platelets and as an indirect indicator of platelet survival. A delay of 24--72 h in recovery, however, has been observed and it has been suggested that aspirin might also inhibit megakaryocyte cyclo-oxygenase. To test this possibility, aspirin (100 mg/kg) or saline were administered i.p. to rats made thrombocytopenic 2 h later (platelet count less than 5% of basal value) by a specific antiplatelet antiserum. Malondialdehyde (MDA) and thromboxane B2 (TxB2) production by platelets was measured by spectrophotometry and radioimmunoassay respectively, during the period of platelet count restoration. By 24 h after thrombocytopenia was induced, platelet count was about 15% of basal values in control and aspirin-treated rats. However, while in controls MDA and TxB2 production was restored to about 20% of basal values, in aspirin-treated rats less than 5% return of activity was detected. A marked difference between the two groups was still found 96 h after induction of thrombocytopenia, when platelet count restoration was similar. Since aspirin disappeared very rapidly from the circulation, the delay in recovery of cyclo-oxygenase activity supports the hypothesis of a megakaryocyte effect of this drug.

Animals↗
PubMed1980

"Aspirinated" platelets are hemostatic in thrombocytopenic rats with "nonaspirinated" vessel walls--evidence from an exchange transfusion model.

The contrasting effects of aspirin on bleeding time (BT) might be related to the drug's inhibitory activity on platelets and vascular prostaglandin I2 (PGI2). To test this, we developed an exchange transfusion model in the rat and studied the BT in animals whose platelets but not vessels had been exposed to aspirin. Rats with severe experimental thrombocytopenia were exchange-transfused with blood from normocythemic rats pretreated with aspirin 6 hr before. The platelet count was raised from 2% to about 70% of basal level and the BT returned to control values even though the platelets neither responded to arachidonic acid nor produced detectable amounts of malondialdehyde and vascular PGI2 was not inhibited. These results indicate that "aspirinated" platelets may be hemostatically active and that the BT is not necessarily affected by unbalanced prostaglandin production in platelets and the vessell wall.

Animals↗
PubMed1979

Quantitative thin-layer chromatographic measurement of n-trifluoroacetyladriamycin-14-valerate (AD 32) and trifluoroacetyladriamycin (AD 41) in blood and tissues.

A thin-layer chromatographic method has been developed for the detection and measurement of N-trifluoroacetyladriamycin-14-valerate (AD 32) and its major metabolite trifluoroacetyladriamycin (AD 41). The procedure gives satisfactory linearity over a large range of concentrations. The coefficient of variability is about 10% over the entire range of usable concentrations, giving good reproducibility; sensitivity is 25 ng for both AD 32 and AD 41. Analysis is specific for AD 32 and AD 41 since adriamycin or more polar metabolites can be differentiated. Recovery is high (85-90%) and the method is simple and economical to use. Pharmacokinetics of AD 32 and AD 41 are reported in blood and some tissues of mice bearing Lewis Lung carcinoma.

Animals↗
PubMed1978

Distribution and antitumor activity of adriamycin given in a high-dose and a repeated low-dose schedule to mice.

Experimental studies on the distribution of adriamycin (AM) under different treatment conditions and possible correlations between tissue and plasma levels and chemotherapeutic activity are discussed. C57BL/6J mice bearing im Lewis lung carcinoma and (C3H x O2O)F1 mice bearing mammary carcinoma were injected iv with AM at a single dose of 15 mg/kg or with the same total amount of drug administered in spaced doses of 3.75 mg/kg for 4 consecutive days. In the two experimental systems studied, the drug reached approximately the same value in the tumor and spleen with both types of treatment, but with the 3.75-mg/kg x 4 schedule much lower AM concentrations were observed in the heart than with the single high-dose treatment. The therapeutic activity of the two treatments also differed: the antitumor and antimetastatic effect was the same in the two tumor systems, but with the 3.75-mg/kg x 4 schedule, increased survival and somewhat lower toxicity were observed. Daunorubicin, tested in the mammary carcinoma system with the two schedules of treatment, behaves very similarly to AM in terms of both distribution and chemotherapeutic effect.

Animals↗
PubMed1977

Cellular and humoral immunity in non-Hodgkin's lymphoma: correlation of immunodeficiencies with clinicopathologic factors.

Immune function was evaluated in 28 non-Hodgkin's lymphoma patients in an attempt to correlate the occurrence of immunodeficiency with the prognostic clinicopathologic factors, lymph-node histology, and clinical stage of disease. Anergy to a battery of recall antigens occurred infrequently (4/28) and only in patients who had Stage IV disease (4/8) (p = less than .004), but did not correlate with lymph-node histology. In contrast to anergy, cellular immunodeficiencies were often detected by lack of response to keyhole limpet hemocyanin immunization in patients regardless of stage. Reductions in at least two of three Ig fractions were found in a third of the patients, with, again, a significantly greater incidence in Stage IV patients (p = less than .005). No significant correlation with histologic type was possible. The response to phytohemagglutinin in vitro was reduced in the patients, but this was of no correlative value.

Antigens↗