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Biomedical subjects

A Martens

Publications and source records attributed to A Martens.

44 records · Page 3Linked to original sources
PubMed1986

Tissue distribution and myelotoxicity of daunomycin in the rat: rapid bolus injection vs continuous infusion.

The pharmacokinetic and cytotoxic behaviour of daunomycin in rats (7.5 mg/kg) when administered as an i.v. bolus injection were compared with those of a 3-hr infusion. After an i.v. bolus injection, the plasma drug levels decreased triphasically (t1/2 alpha = 0.8 min, t1/2 beta = 29.6 min and t1/2 gamma = 9.9 hr). The organs showed two types of concentration/time curves. One was found in the lungs, liver, kidneys and heart and had an initial high drug concentration followed by a relatively rapid elimination. The other was shown by the hemopoietic tissues (spleen and bone marrow): the drug uptake phase lasted longer (about 1.5 hr) and the elimination was slower. In general, daunomycin infusion led to substantially lower plasma and tissue levels, including in the heart, liver and kidneys. Again the hemopoietic tissues behaved in a different way: in spleen and bone marrow almost equal drug levels were obtained after daunomycin infusion as compared to a bolus injection. The myelotoxicity after daunomycin treatment was assessed by CFU-S (colony forming units-spleen) survival: the bolus injection killed as many CFU-S as did infusion (mean +/- S.D.: 11.8 +/- 5.3 CFU-S survival versus mean +/- S.D.: 13.5 +/- 2.4). Thus, it can be predicted that daunomycin infusion will lead to less cardiotoxicity but to an equal bone marrow suppression.

Animals↗
PubMed1985

Differences in the pharmacokinetics of daunomycin in normal and leukemic rats.

We compared the pharmacokinetics of daunomycin (7.5 mg/kg i.v. bolus injection) in normal and leukemic rats using a leukemia model which resembles acute myeloid leukemia in humans. Due to a more rapid decrease in plasma concentration, the area under the plasma concentration/time curve (AUC) for up to 2 h after drug injection was smaller (2.2 times) in the leukemic rats than that for normals. However, due to higher plasma levels during the drug elimination phase, the total AUC0----infinity was somewhat larger (1.3 times) in the leukemic rats. In the leukemia-infiltrated organs (spleen, liver, and lungs), significantly higher daunomycin concentrations (per gram wet weight) were found than in those obtained from normal rats. In contrast, femoral bone marrow from leukemic rats contained less daunomycin (per 10(9) nucleated cells) than did normal marrow. Quantification of the daunomycin uptake in vitro by flow cytometry showed that leukemic cells from bone marrow and spleen have an equal net drug uptake. Our data suggest that, in the presence of a high leukemic cell load, the intravenously injected daunomycin is rapidly taken up and retained by the leukemic tumor mass in, e.g., spleen, liver, and lungs, and that, as a consequence of this, the femoral marrow functions as a kind of pharmacological sanctuary.

Animals↗
PubMed1984

Repeated daunomycin administration in rats. Pharmacokinetics and bone marrow toxicity.

In the experiments described here, rats received three IV bolus injections (7.5 mg/kg) of daunomycin. The plasma data obtained after a single IV injection could be described by a two-compartment open model with t1/2 alpha and t1/2 beta values of 18.4 and 472.1 min. Of the tissues, the lungs contained the most daunomycin per gram of tissue, followed by the kidneys, liver, heart, and spleen. Daunomycinol was the main metabolic product and no substantial differences were found in daunomycinol content among the different organs. For all tissues and plasma, higher drug concentration values than would be expected on the basis of accumulation alone were observed after the second but not after the third injection. The cumulative urine excretion of daunomycin and daunomycinol remained essentially unchanged after one, two, and three daunomycin injections. However, the cumulative bile excretion increased after repeated daunomycin administration. The experiments in which the myelotoxicity was assessed by CFU-S survival after daunomycin treatment showed that three successive daunomycin administrations lead to a proportional reduction in stem cells.

Animals↗
PubMedDate not supplied

T-cell evaluation in patients with colon cancer: dinitrochlorobenzene skin testing versus plasma levels of sIL-2r and sCD8.

BACKGROUND: Developing reliable methods to test the T-cell system may be important in the treatment of colon cancer patients with 5-fluorouracil/levamisole. In a pilot study we explored whether DNCB (dinitrochlorobenzene) skin testing correlated with plasma levels of soluble interleukin-2 receptor (sIL-2r) and soluble CD8 (sCD8) and, secondly, whether the application of DNCB had any influence on the production of sIL-2r and sCD8. METHODS: In 10 patients with advanced colon cancer and in 10 healthy volunteers, plasma levels of sIL-2r and sCD8 were measured before and 10 days after the application of 2 mg DNCB on the inner side of the forearm. RESULTS: As expected, colon cancer patients showed a depressed immune system compared to healthy volunteers (DNCB skin test: P = .005, sIL2r [medians 700 vs 295, P = .002], sCD8 [medians 158 vs 90, P = .03], M-W test). The plasma levels for sIL-2r and sCD8 were significantly lower in the skin-positive cases (P = .01 and P = .03, M-W test). However, a large overlap in plasma levels could be observed between the two skin categories. DNCB had no influence on the production of sIL-2r and sCD8; median change skin-negative and skin-positive -10 vs +25, P = .14, respectively; 48 vs 0, P = .32 (M-W test). CONCLUSIONS: DNCB skin testing and plasma levels of sIL-2r and sCD8 seem to be equally useful in evaluating the T-cell system and can be used simultaneously.

Adjuvants, Immunologic↗
PubMedDate not supplied

Polymerase chain reaction analysis of the surgical margins of equine sarcoids for bovine papilloma virus DNA.

OBJECTIVE: To examine apparently normal skin around equine sarcoids for evidence of bovine papilloma virus (BPV) DNA, and to relate this finding to the observed recurrence after surgery. STUDY DESIGN: Prospective study. ANIMALS OR SAMPLE POPULATION: Forty-one equine sarcoids from 19 horses. MATERIALS AND METHODS: The tumors were surgically excised at a measured distance of 8, 12, or 16 mm. Samples from the tumor and of the entire surrounding skin were taken at 4, 8, 12, and 16 mm from the tumor border and analyzed for the presence of BPV DNA using polymerase chain reaction (PCR) amplification. The samples were grouped per examined sarcoid, and a tumor was considered positive at a certain distance as soon as at least one of the samples at that distance was positive. The clinical outcome was recorded for each sarcoid after a minimal follow-up of 6 months. RESULTS: All sarcoids were positive for BPV(1) or BPV(2). The tumor margin was positive at 4, 8, 12, and 16 mm in, respectively, 95%, 73%, 39%, and 33% of the examined sarcoids. Local recurrence was observed in 3 sarcoids on 3 different horses. From survival analysis, there was a greater likelihood for local recurrence when sarcoids had a surgical margin that was positive for BPV DNA. CONCLUSIONS AND CLINICAL RELEVANCE: BPV DNA is often detected in visibly normal skin around sarcoids, and there is a significantly greater probability for local recurrence when the surgical margins are positive for the presence of BPV DNA.

Animals↗