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Biomedical subjects

T Colombo

Publications and source records attributed to T Colombo.

At least 109 records · Page 6Linked to original sources
PubMed1981

Differential adriamycin distribution to blood components.

The differential distribution of doxorubicin (Adriamycin = AM) and daunorubicin (Daunomycin = DM) within the blood components, after an i.v. injection of 10 or 15 mg/kg of body weight, was investigated from its metabolites and quantified by means of the TLC scanning fluorescence technique. AM accumulated in the following order (of decreasing percentages): plasma and red cells (RBC), white cells (WBC), and platelets (PT), but the absolute amount of drug that reached each cell type was related to its relative volume. In the presence of higher blood concentrations (after injection of 15 mg/kg of body weight) the RBCs accumulated much more AM than the plasma, WBC, and PT; suggesting that the RBC fraction has a greater capacity to concentrate the drug. However, if the concentration of AM is expressed per unit volume of each component, a markedly higher value was observed for PT, and this was confirmed by in vitro results obtained by incubating blood in the presence of AM. DM seemed to be distributed on a percent basis to a greater extent than AM in the RBC fraction. Both compounds were taken up by blood cells, particularly platelets, to levels in excess of the extracellular concentration.

Animals↗
PubMed1981

Pharmacodynamic model describing the growth of a mammary carcinoma in the mouse under the influence of adriamycin treatment.

The chemotherapeutic effects of different doses of adriamycin in (C3H x 020)F1 mice bearing mammary carcinoma have been investigated and a model of the growth of neoplastic cells under the influence of treatment is described. An estimate of cell kill and of the fraction of cells surviving after treatment is given by the efficacy constant K, which is a function of the dose level of the drug. The therapeutic value of each treatment is, however, also related to the degree of toxicity which in our model is expressed by the probability of death for each dose level.

Animals↗
PubMed1981

Interaction between heparin and adriamycin in mice bearing the Lewis lung carcinoma.

The investigation was prompted by the observation that adriamycin can interact with heparin in vitro and reduces its anticoagulant activity in ex vivo tests in humans. The possible interactions between these two drugs were studied in C57Bl/6J mice bearing the Lewis Lung Carcinoma (3LL). The anticoagulant activity of heparin was temporarily reduced by concomitant treatment with adriamycin, as indicated by both activated partial thromboplastin times and blood recalcification times. In contrast, no changes were found in the kinetics of adriamycin disappearance from blood and accumulation in tissues if mice had been pretreated with heparin. Moreover, the effect of adriamycin on tumour and metastasis growth was unchanged by the association with the anticoagulant. These data indicate that the short-lived interaction between adriamycin and heparin, which can be documented by coagulation tests, does not necessarily involve a modification in the anticancer activity of the anthracycline.

Animals↗
PubMed1978

The effect of outreach workers' services on the medical care utilization of a disadvantaged population.

An original goal of the Kaiser-Permanente Neighborhood Health Center Project was to organize the project so that a medically indigent population would be able to utilize fully and appropriately the services of a complex medical care program. A special program of outreach services was designed as the principal means to achieve this goal. This study was made to determine the effects of these outreach services on (1) the use of or nonuse of ambulatory care services; (2) the volume and type of services used; (3) the patterns of use; and (4) the appointment-keeping behavior of the project population for a 12-month period. Outreach and medical care services were provided to an average of 7,000 persons in 1,500 low-income families who were enrolled as health plan members in the Kaiser-Permanente Medical Care Program. Project participants were randomly divided into two groups, one with and one without services, and utilization data were collected from their medical and administrative records. The findings suggest that outreach intervention had a positive effect on access to care. Persons who received outreach services were more likely to contact the medical care system; these persons also showed a substantial difference in the volume of services they used, when compared to those without outreach services. Outreach workers were less successful in changing utilization patterns, although slight differences were found in the direction of more appropriate use. Persons with outreach services were more likely to have made contacts with their regular physician, to have made a smaller proportion of walk-in contacts, to have had a higher proportion of regularly scheduled contacts, and to have made a higher proportion of continuing visits. Outreach workers also had little or no effect on appointment-keeping behavior.

Adolescent↗
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

Differential distribution of antitumor agents in primary and secondary tumors.

The differential distribution of a series of antineoplastic agents in metastatic tissues compared to their respective primary tumors has been investigated in one rat and two mouse experimental tumor systems, ie, the intramuscular Lewis lung carcinoma (3LL) of C57BL/6 mice, which gives rise to spontaneous lung metastases, the intratibial Sarcoma 180 (S180) of CD1 mice, which induces macroscopic metastases to the lymph nodes, and the Walker 256 carcinosarcoma of CD rats, which also metastasizes to the lymph nodes. The results described in this paper show that the concentrations of adriamycin, daunorubicin, cyclophosphamide and its alkylating metabolites, hydroxyurea, 1-methyl-1-nitrosourea, and 6-mercaptopurine are much higher in the pulmonary metastases of 3LL and/or in the lymph node metastases of S180 than the concentrations measured in the primary tumor. In the Walker 256 tumor system the distribution of adriamycin appears to follow the same pattern observed for the mouse tumors. Only for methotrexate (in the 3LL tumor) is the difference in the concentrations at the two sites not so evident. These findings are discussed in relation to the comparatively greater sensitivity of metastases to chemotherapy.

Animals↗
PubMed1976

Effect of phenobarbital on cyclophosphamide metabolism in rats.

1. The pharmacokinetics of cyclophosphamide and its alkylating metabolites have been studied in rats whose liver microsomal enzymes had been induced by phenobarbital pre-treatment. 2. Serum levels of cyclophosphamide were determined using a new g.l.c. method. The half-life of cyclophosphamide in blood of rats pre-treated with phenobarbital was shorter than in control rats. This change is closely related to higher rates of production of p-nitrobenzylpyridine-positive alkylating metabolites of cyclophosphamide, which in turn is followed by their more rapid disappearance from the circulation. 3. Urinary excretion reflects this situation; lower amounts of cyclophosphamide and higher concentrations of its alkylating metabolites are present in the urine of phenobarbital-treated rats. 4. Perfusion of livers isolated from phenobarbital-pre-treated rats confirmed the results in vivo. With this preparation, too, disappearance of cyclophosphamide was more rapid and formation of its alkylating metabolites was accelerated after phenobarbital treatment.

Alkylating Agents↗
PubMed1976

Importance of pharmacokinetic studies on cyclophosphamide (NSC-26271) in understanding its cytotoxic effect.

Pharmacokinetic studies on cyclophosphamide (CP) and its alkylating metabolites produced by hepatic biotransformation have been performed in vivo in animals and in vitro in the perfused liver. CP levels were determined by a gas-chromatographic method combined with mass-spectrometry, and production of alkylating metabolites was assayed by the 4-(4-nitrobenzyl)pyridine reaction for alkylating compounds. Differenes in serum drug levels between normal rats and rats bearing Walker 256 carcinosarcoma were observed in vivo and were confirmed by the liver-perfusion technique. Pharmacokinetic parameters and enzyme kinetic data both in normal and in tumor-bearing animals will be presented. The disappearance of CP and the corresponding formation of CP metabolites was significantly modified when (a) CP was given after previous treatment with a compound which alters its biotransformation (ie, phenobarbital, an inducer of microsomal metabolism), (b) CP was given after previous treatment with CP (which inhibits microsomal metablism), or (c) CP was given with competitive substrates of aldehyde oxidase or dehydrogenase (glyceraldehyde, chloral hydrate, and disulfiram). Results obtained in animals or in the perfused liver will be discussed. The significance of this modified CP metabolism in influencing its cytotoxic effect will be discussed and correlations between drug levels and activity will be presented.

Animals↗
PubMedDate not supplied

Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice.

The interaction between cyclophosphamide (CPA) and phenobarbital (PB) was investigated in B6D2F1 mice, checking both the antileukemic and immunosuppressive activity together with the serum levels of CPA and its metabolites. A reduced cytotoxic activity of CPA has been observed when PB is given for 2 days before CPA and an interval of at least 6 hours elapses between the last treatment of PB and the administration of CPA. On the contrary, when PB is given simultaneously with CPA for 2 or 4 consecutive days, an increased antileukemic activity of CPA occurs. In the experimental condition where PB decreases the activity of CPA, serum levels of CPA, assayed by means of a new specific gas-chromatographic method, and of its NBP-alkylating metabolites, indicate that this effect may be explained on a pure pharmacokinetic basis. However, for the situation where an increased effect of CPA was observed under the influence of PB, pharmacokinetic data did not provide a clear explanation.

Animals↗