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Biomedical subjects

H Olsen

Publications and source records attributed to H Olsen.

At least 37 records · Page 2Linked to original sources
PubMed1999

The role of sulphonylurea in combination therapy assessed in a trial of sulphonylurea withdrawal. Scandinavian Insulin-Sulphonylurea Study Group Research Team.

AIMS: To evaluate the effect of adding insulin to sulphonylurea (SU) and the effect of SU withdrawal on glycaemic control in Type 2 diabetic patients who failed on treatment with SU alone. METHOD: One hundred and seventy-five patients were included in a placebo-controlled multicentre study. During phase I (4 months), premixed insulin was added to glibenclamide therapy; during phase II (1-4 months, depending on response) the insulin dose was fixed, while placebo or glibenclamide replaced the open SU therapy. Insulin sensitivity (KITT), beta-cell function (C-peptide) and metabolic control (HbA1c) were monitored. RESULTS: HbA1c improved from 9.65% to 7.23% (P < 0.0001) during phase I. A high HbA1c value (P < 0.0001) and a high KITT-value (P = 0.045) at baseline were associated with a beneficial response to combination treatment. During phase II, glycaemic control was unchanged in the control (glibenclamide) group. In the placebo group, after SU withdrawal, fasting blood glucose (FBG) increased by 10% or more within 4 weeks in 79% of the patients. Patients (67 of 112) with an FBG increase > or =40% during phase II were defined as 'SU responders' by protocol. In a multivariate analysis only a long duration of diabetes was associated with SU response. There were more GAD-antibody-positive patients among non-responders (18% vs. 4%, P = 0.0263). CONCLUSIONS: Poor glycaemic control in combination with preserved insulin sensitivity and lack of GAD antibodies predicts a beneficial response to combination therapy, which can be achieved in 75% of patients with SU failure.

Adult↗
PubMed1999

Adverse drug reactions in current antihypertensive therapy: a general practice survey of 2586 patients in Norway.

The objective of this study was to determine the frequency and profile of adverse reactions to antihypertensive drugs in an unselected group of drug-treated hypertensive patients. A questionnaire-based survey was carried out among 2586 drug-treated hypertensive patients who attended a general practitioner for clinical control. Adverse drug reactions reported spontaneously, upon general inquiry, upon specific questioning and as evaluated by a physician were used as the main outcome measures. The study shows that the percentage of patients who reported adverse drug reactions spontaneously, upon general inquiry and upon specific questioning were 16%, 24% and 62% respectively. Users of diuretics reported the lowest frequency of adverse reactions, whereas users of beta-blockers reported the highest frequency. In 7% of the patients, the adverse drug reactions were of such a nature that the physicians considered discontinuing the treatment. As a conclusion, the reported frequency of adverse drug reactions in antihypertensive treatment is high, but with significant differences between the various drug groups. Monotherapy is connected with far fewer adverse drug reactions than combination therapy.

Adult↗
PubMed1998

4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family.

Translation initiation in eukaryotes is mediated by the cap structure (m7GpppN, where N is any nucleotide) present at the 5' end of all cellular mRNAs, except organellar. The cap is recognized by eukaryotic initiation factor 4F (eIF4F), which consists of three polypeptides, including eIF4E, the cap-binding protein subunit. The interaction of the cap with eIF4E facilitates the binding of the ribosome to the mRNA. eIF4E activity is regulated in part by two translational repressors, 4E-BP1 and 4E-BP2, which bind to it and prevent its assembly into eIF4F. We report here the isolation of 4E-BP3, a new member of the 4E-BP family. 4E-BP3 is homologous to 4E-BP1 and 4E-BP2, exhibiting 57 and 59% identity, respectively. The homology is most striking in the middle region of the protein, which contains the eIF4E binding motif and residues that are phosphorylated in 4E-BP1. 4E-BP3 is a heat stable protein that binds to eIF4E in vitro as well as in vivo. Further, 4E-BP3 overexpression specifically reduces eIF4E-dependent translation. The overlapping function and expression of the different 4E-BP family members imply that there is redundancy in this translational control mechanism, underscoring its importance.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein.

All eukaryotic mRNAs (except organellar) are capped at their 5' end. The cap structure (m7GpppN, where N is any nucleotide) is extremely important for the processing and translation of mRNA. Several cap-binding proteins that facilitate these processes have been characterized. Here we describe a novel human cytoplasmic protein that is 30% identical and 60% similar to the human translation initiation factor 4E (eIF4E). We demonstrate that this protein, named 4E Homologous Protein (4EHP), binds specifically to capped RNA in an ATP- and divalent ion-independent manner. The three-dimensional structure of 4EHP, as predicted by homology modeling, closely resembles that of eIF4E and site-directed mutagenesis analysis of 4EHP strongly suggests that it shares with eIF4E a common mechanism for cap binding. A putative function for 4EHP is discussed.

Amino Acid Sequence↗
PubMed1998

[Adverse effects of zopiclone].

In 1994 zopiclone (Imovane), a cyclopyrrolon, was introduced in Norway as a new kind of hypnotic. In 1996 zopiclone had a 26% share of the hypnotic market. This review of relevant literature has revealed a lack of documentation on the adverse effects of zopiclone. The similarities between zopiclone and benzodiazepine hypnotics are more striking than the differences. The bulk of comparative research has been carried out with triazolam, a drug taken off the Norwegian market in 1991. With zopiclone there is less inhibition of psychomotor function the day after intake than with flunitrazepam. Zopiclone causes less subjective "hangover" than nitrazepam, but there is a similar inhibition of psychomotor function the day after intake, and in some cases greater addictive potential.

Azabicyclo Compounds↗
PubMed1998

2,3,7,8-Tetrachlorodibenzo-p-dioxin mechanism of action to reduce lipoprotein lipase activity in the 3T3-L1 preadipocyte cell line.

Lipoprotein lipase (LPL) is important in the process of triglyceride storage in adipose tissue. Depression of LPL activity in adipose tissue is associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced wasting syndrome and may have a role in the associated serum hyperlipidemia produced by TCDD. The 3T3-L1 cell line was used as an in vitro model, independent of hormonal, nutritional, or other interfering factors associated with in vivo studies, in order to systematically examine the mechanism of action of TCDD. TCDD produced a statistically significant (P < 0.05) time- and dose-dependent decrease in LPL activity. Results of experiments with Ah-receptor blockers and structure activity studies with different polychlorinated biphenyl (PCB) and dioxin congeners were consistent with reduction of LPL activity being mediated by the Ah receptor. Culturing of 3T3-L1 cells without glucose or with cytochalasin B, a blocker of facilitative glucose transporters (GLUT), was effective in reducing LPL activity (P < 0.05). TCDD did not further reduce LPL activity in cytochalasin B pretreated 3T3-L1 cells or in 3T3-L1 cells cultured in glucose-free media. Dexamethasone pretreatment, which is known to increase GLUT expression in 3T3-L1 cells, prevented the reduction of LPL activity by TCDD. Protein tyrosine kinase activities, assayed using gamma-32P-ATP and RR-SRC, a src specific peptide substrate, were significantly increased (P < 0.05) over control levels by both TCDD and glucose deprivation. Furthermore, results of experiments treating 3T3-L1 cells with either insulin, EGF, 8-Br-cAMP, TPA, or genistein, alone or in combination with TCDD, were generally consistent with the hypothesis that lowered intracellular glucose and altered cellular kinase activities may be involved in reduction of LPL activities by TCDD. Further work is needed to confirm and better understand the role protein phosphorylation plays in TCDD-mediated alteration of glucose disposition and LPL activity. In summary, TCDD reduced LPL activity in 3T3-L1 cells as seen in vivo. Manipulation of glucose transport through a number of experimental approaches produced changes in 3T3-L1 LPL activity consistent with results of previous investigators showing glucose to be a positive regulator of LPL activity and consistent with our hypothesis that TCDD-mediated reduction of glucose transport is an important factor in the down regulation of LPL activity by TCDD.

3T3 Cells↗
PubMed1998

Reduced venous compliance in lower limbs of aging humans and its importance for capacitance function.

Venous compliance in the calf of humans and its importance for capacitance function in relation to age were studied with the aid of 22, 44, and 59 mmHg lower body negative pressure (LBNP). Negative pressure transmission to the calf as well as changes in calf volume were studied, and venous compliance was calculated [change in volume with pressure change (dV/dP)]. The change in capacitance response of the calf with age (20-70 yr) was evaluated during LBNP 44 mmHg. Transmission of negative pressure to the subcutaneous tissue was almost full without any changes with age (92%). However, it was reduced to 80% in the underlying muscle tissue, irrespective of depth. Venous compliance in the young was 0.051 ml . 100 ml-1 . mmHg-1 and was reduced by 45% to 0.029 ml . 100 ml-1 . mmHg-1 in the old (P < 0.05). Accordingly, the capacitance response was reduced by 0.015 ml . 100 ml-1 . yr-1 (P < 0.005). Furthermore, the hemodynamic response to hypovolemic circulatory stress was attenuated with age. The reduced pressure transmission in muscle tissue is probably due to restriction of the muscle fascia envelope. The reduced venous compliance with age and the concomitant reduction in capacitance response during LBNP have implications for both the sympathetic reflex responses as well as the capacitance response during acute hypovolemic circulatory stress, which might be defected in aging humans.

Adult↗
PubMed1997

[Statins--the pattern of adverse effects with empahsis on mental reactions. Data from a national and an international database].

We report on adverse drug reactions to statins recorded internationally and in Norway. The use of HMG-CoA reductase inhibitors (statins) has increased with a factor of 30 in Norway over the period 1989-96. Recently published clinical trials conclude that statins are safe; adverse drug reactions being infrequent and non-serious. The reactions observed are mostly increased hepatic enzymes and myopathy. Data from the Norwegian spontaneous reporting system, and from WHO's international database covering the period of 1988-95, includes reports of adverse drug reactions relating to other organ systems, such as the nervous system, the gastrointestinal tract, skin and cardiovascular organs. Psychiatric disorders represent 15% of the reactions to statins in the Norwegian database. Reactions include aggression, nervousness, depression, anxiety, sleeping disorders and impotence. The pharmacological mechanisms are not elucidated, but may be an effect of falling serum cholesterol.

Adult↗
PubMed1997

The human homologue of the yeast Prt1 protein is an integral part of the eukaryotic initiation factor 3 complex and interacts with p170.

Eukaryotic initiation factor 3 (eIF3) is a large multisubunit complex that stabilizes the ternary complex, eIF2 x GTP x tRNA(Met)i and promotes mRNA binding to the 40 S ribosomal subunit. eIF3 also functions as a ribosome subunit anti-association factor. The molecular mechanisms by which eIF3 exerts these functions are poorly understood. We describe here the cloning of the cDNA encoding the human homologue of the yeast eIF3 subunit Prt1. The human PRT1 cDNA encodes a protein of predicted molecular mass of 98.9 kDa that migrates at 116 kDa on SDS-polyacrylamide gels. Human and yeast Prt1 share 31% identity and 50% similarity at the amino acid level. The homology is distributed throughout the entire protein, except for the amino terminus, and is particularly high in the central portion of the protein, which contains a putative RNA recognition motif. hPrt1 is recognized by an antibody raised against eIF3, and an affinity-purified antibody to recombinant hPrt1 recognizes a protein migrating at 116 kDa in a purified eIF3 preparation. Far Western analysis shows that hPrt1 interacts directly with the p170 subunit of eIF3. Mapping studies identify the RNA recognition motif as the region required for association with p170. Taken together, these experiments demonstrate that hPrt1 is a component of eIF3. Our data, combined with those of Hershey and co-workers, suggest that mammalian eIF3 is composed of at least 10 subunits: p170, p116 (hPrt1), p110, p66, p48, p47, p44, p40, p36, and p35.

Amino Acid Sequence↗
PubMed1997

Biophysical factors and contractile function during coronary bolus perfusion: an experimental study in the isolated guinea pig heart.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the role of biophysical factors (viscosity, temperature, osmalality, perfusion pressure, and ionic washout) on cardiac contractility during coronary bolus perfusions. METHODS: Guinea pig hearts were perfused in the osmolality mode at constant and high flow (30 mL/min) and were subjected to boluses (injected in 1-8 seconds) of purely nonionic media: mannitol and iohexol (in hyposmolal, isosmolal, and twice isosmolal forms) and iodixanol (in a hyposmolal form). RESULTS: All contrast media elicited a dose-dependent increase in aortic pressure and contractile variables that was attenuated by an increased osmolality. Elevation of aortic pressure was followed by an increase in left ventricular systolic pressure and, with iodixamol and iohexol, a subsequent elevation of left ventricular end-diastolic pressure. Moderate hypothermic solutions (29 degrees C) did not alter the responses. The ionic washout profile was the same for the three substances, as were the individual washout profiles for sodium, potassium, chloride, magnesium, and calcium. CONCLUSION: An increase in osmolality attenuates the increased contractility induced by a purely nonionic medium. A viscosity-induced rise in perfusion pressure may increase contractility. A moderate reduction in bolus temperature does not alter the contractile responses. The ionic washout profile is the same for the main cardioactive electrolytes.

Animals↗
PubMed1997

Decreased capacitance response with age in lower limbs of humans--a potential error in the study of cardiovascular reflexes in ageing.

The cardiovascular regulation in humans depends to a major extent on sympathetic reflexes originating from volume receptors in the arterial as well as the cardiopulmonary region. With experimental approaches, such as lower body negative pressure (LBNP) and tilting, signs of reduced efficiency with ageing have been shown. However, a confounding factor may be an age-related decline in venous capacitance response of the lower limbs, reducing the decrease in central blood volume and thus the deactivation of baro/cardiopulmonary receptors. This potential error was addressed in the present study. Central hypovolaemic stress was produced by LBNP 60 cmH2O in 10 young (mean age 23, range 20-25 years) and 10 old males (mean age 65, range 61-70 years). Changes in tissue volume of the calf were studied by strain gauge volumetric technique. Transmission of negative pressure to the calf muscle was studied in two young and two old volunteers. The haemodynamic response to hypovolaemic circulatory stress was attenuated in the old as compared with the young subjects, with a less marked increase in heart rate and peripheral resistance. Further, in the old subjects, the decrease in systolic blood pressure, pulse pressure and forearm blood flow was attenuated. Transmission of negative pressure to the calf was equal in both groups. The capacitance response was reduced with age from 2.27 +/- 0.14 to 1.64 +/- 0.13 mL 100 mL-1 (P < 0.005). However, the net capillary fluid filtration was unchanged. The reduced capacitance function might partly explain the declining reflex responses with age in humans, and thus seems to be of considerable importance when studying cardiovascular sympathetic reflex responses in ageing.

Adult↗
PubMed1997

Value of intraoperative keratometry in predicting outcome of radial keratotomy.

PURPOSE: To investigate whether the immediate change in corneal power during radial keratotomy correlates with the long-term postoperative change in subjective refraction, and thereby being predictive for refractive outcome. METHODS: Manual keratometry was performed on 45 consecutively operated eyes of 45 young persons with myopia of 5 dioptres and less and immediately after radial keratotomy. Automated keratometry and subjective spherical equivalent refraction were investigated during a follow-up period of 6 months and correlated to the intraoperative keratometric measurements. RESULTS: On average, the majority of the change in corneal curvature after radial keratotomy took place within 1 min. There was no correlation between the intraoperative curvature change and the changes in curvature measured up to 6 months after surgery. There was a weak significant positive correlation between intraoperative curvature change and the change in subjective refraction at 6 months after surgery (R = 0.48, p < 0.01). The prediction error in estimating subjective refractive changes from intraoperative keratometry changes was, however, similar in patients who had bilateral radial keratotomy. Inclusion of such fellow-eye information together with the age of the patient in a multiple linear regression analysis increased the correlation coefficient from 0.48 to 0.75. CONCLUSIONS: The change in central corneal curvature takes place within minutes after corneal incision. As a single parameter, intraoperative keratometry cannot be used for titrating surgery. Information from the results of first eye radial keratotomy surgery with intraoperative keratometry is, however, predictive for radial keratotomy in the second eye. These findings suggest that a large source to refractive variability after radial keratotomy is related to individual patient factors, such as corneal biomechanics and wound healing.

Adult↗
PubMed1997

Comparison of objective methods for quantifying the refractive effect of photo-astigmatic refractive keratectomy using the MEL-60 excimer laser.

PURPOSE: To investigate the accuracy and precision of automated keratometry, automated refractometry, and computerized corneal topography in estimating the subjective refractive outcome of photo-astigmatic refractive keratectomy six months postoperatively. METHODS: Photo-astigmatic refractive keratectomy (Aesculap-Meditec, MEL-60 Excimer Laser) was performed on 26 eyes with a preoperative myopia ranging from -4.0 to 7.6 dioptres, and a naturally occurring astigmatism from 0.75 to 5.0 dioptres. Six months postoperatively refractive outcome was evaluated by automated keratometry, automated refractometry (Nikon NRK-8000), computerized topography (TMS-1), and subjective refraction. Estimate errors were computed as the difference between the change in subjective refraction and the change in automated keratometry, automated refractometry, and surface topography, respectively. Astigmatic changes were evaluated by the second harmonic component in the Fourier series analysis. RESULTS: Subjective spherical as well as cylindrical values were reduced significantly six months postoperatively. The estimate error (mean +/- one standard deviation) for automated keratometry was -1.26 +/- 0.72 dioptres for the spherical equivalent and -1.36 +/- 1.02 dioptres for the cylinder; for automated refractometry it was -0.78 +/- 0.91 dioptres for the spherical equivalent and -0.66 +/- 0.92 dioptres for the cylinder. The best estimates of subjective changes were obtained when the average of ring 2 and 3 of the topographic data was used: -0.15 +/- 0.82 dioptres for the spherical equivalent and -0.78 +/- 0.80 dioptres for the cylinder. CONCLUSIONS: The computerized topographer with the Fourier analysis was superior to automated keratometry and automated refractometry in estimating the subjective spherical refractive outcome and comparable to automated refractometry in estimating the subjective cylinder refractive outcome after photo-astigmatic refractive keratectomy.

Adult↗
PubMed1996

[Centenarians in the county of Funen. Morbidity and functional capacity].

The aim was to examine the feasibility of a study of centenarians and to describe morbidity and functional capacity of centenarians in the County of Funen. A total of 51 out of 58 centenarians on Funen born on May 1, 1894 or before participated. An interview could be carried out almost completely in 80.4% of the 51 participants, cognitive testing (MMSE) in 78.4% and physical performance test (PPT) in 49%. Additional information on morbidity and activities of daily living (ADL) was collected on all 51 centenarians from family members, nursing staff, GP's, hospital registries and the National Cancer Registry. Almost 3/4 were women and 58.8% were in an old people's home. Osteoarthrosis, urinary incontinence, heart failure, dizziness and eye diseases were found to be frequently prevalent, while hypertension, diabetes, cancer and stroke were found to be rare. Based on Katz' ADL index approx. 1/3 could be considered to be independent of help, while almost everybody was dependent on help for the instrumental activities (IADL). A low average score was found at the PPT, especially the walking speed was found to be very slow. Only 32.5% scored over 23 points at the MMSE, but allowing for severe impairment of vision and hearing more than 1/3 were found to be cognitively well-functioning. Severe dementia was found among 15.7%. Dependency on help for the ADL-functions was not found to be associated with health measurement, but strongly associated with visual function, PPT and MMSE (p < 0.001). The characterization of centenarians as described in a number of foreign studies as being an homogeneous, relatively healthy and independent group could therefore not be confirmed. On the contrary, they were found to be very heterogeneous and characterized by multi-morbidity. By far the great part of them were in addition dependent on help in their activities of daily life. Approx. 1/3, however, were found to be relatively independent of help for basic functions, more than 1/3 were cognitively well-functioning, and a very small number could even manage a few outdoor functions by themselves.

Activities of Daily Living↗
PubMed1996

In vivo modulation of 17 beta-estradiol-induced vitellogenin synthesis and estrogen receptor in rainbow trout (Oncorhynchus mykiss) liver cells by beta-naphthoflavone.

Vitellogenesis or egg yolk production represents a key estrogen initiated process in oviparous vertebrates which is crucial for oocyte maturation. Previous in vitro studies have shown that cytochrome P4501A1 (CYP1A1)-inducing compounds such as beta-naphthoflavone (betaNF) modulate 17 beta-estradiol-induced vitellogenin (Vg) synthesis in primary cultures of juvenile rainbow trout liver cells. In this study, treatment of juvenile trout with 0.5 mg/kg 17 beta-estradiol plus either 25 or 50 mg/kg betaNF confirmed in vivo that betaNF may depress Vg synthesis by the liver. Alternatively, trout treated with 0.5 mg/kg 17 beta-estradiol plus 12.5 mg/kg betaNF or 5 mg/kg 17 beta-estradiol plus 12.5, 25, or 50 mg/kg betaNF showed a potentiation of Vg synthesis relative to estradiol-only injected fish. These results are significant as they suggest that changing plasma estrogen levels in sexually maturing trout will determine whether or not CYP1A1-inducing compounds may suppress, have no effect, or potentiate estrogen-induced liver Vg synthesis. Depressed Vg synthesis by trout injected with 0.5 mg/kg 17 beta-estradiol plus 50 mg/kg of betaNF correlated with depressed estrogen-binding capacity of liver, as assessed by [3H]17 beta-estradiol binding to liver nuclear protein extracts. Using gel mobility shift assay, the decrease in estrogen responsiveness of liver was not attributed to depressed estrogen response element-estrogen receptor binding. The fish liver vitellogenesis process offers a comparative model with which to further study the mechanism(s) of aryl hydrocarbon receptor-mediated antiestrogenicity and endocrine disruption.

Animals↗
PubMed1996

Formation of meprobamate from carisoprodol is catalysed by CYP2C19.

Carisoprodol is a muscle relaxant analgesic, which has an active metabolite i.e. meprobamate. We conducted an open three-panel single-dose administration study with 15 healthy volunteers: five poor metabolizers of mephenytoin, five poor metabolizers of debrisoquine and five extensive metabolizers of both substrates. The aim was to investigate if the elimination of carisoprodol and meprobamate is dependent on the two metabolic polymorphisms of mephenytoin and debrisoquine. The subjects were given single oral doses of 700 mg carisoprodol and 400 mg meprobamate on separate occasions. The disposition of carisoprodol was clearly correlated to the mephenytoin hydroxylation phenotype. The mean serum clearance of carisoprodol was four times lower in poor metabolizers of mephenytoin than in extensive metabolizers, which confirms the hypothesis from our previous study that N-dealkylation of carisoprodol cosegregates with the mephenytoin hydroxylation polymorphism. However, mean serum clearance of meprobamate did not differ between the two groups. Also, polymorphic debrisoquine hydroxylation did not influence the elimination of carisoprodol or meprobamate. Poor metabolizers of mephenytoin thus have a lower capacity to metabolize carisoprodol and may therefore have an increased risk of developing concentration dependent side-effects such as drowsiness and hypotension, if treated with ordinary doses of carisoprodol.

Administration, Oral↗
PubMed1996

Pretreatment with ischaemia attenuates acute epirubicin-induced cardiotoxicity in isolated rat hearts.

We investigated whether a brief ischaemic episode (ischaemic pretreatment) preconditioning might attenuate the acute cardiotoxicity of the anthracycline, epirubicin. Isolated rat hearts perfused at a constant flow rate of 10 ml/min, were preconditioned with 5 min. of global ischaemia and 10 min. of reperfusion (preconditioned hearts), or were perfused for 15 min. (control hearts). The hearts were then subjected to 20 min. of infusion with epirubicin (2 mg/ml) or vehicle by a side arm of the perfusion system at a rate of 0.1 ml/min. (0.2 mg epirubicin/min.). Attenuation of cardiotoxicity of a total dose of 4 mg of epirubicin was assessed by functional and metabolic parameters during infusion and during the following 30 min. recovery period. Cardiotoxic effects were reduced in preconditioned hearts compared to control hearts. Thus left ventricular developed pressure and heart rate product after 20 min. of epirubicin infusion was depressed to 27 +/- 7% (mean +/- S.D.) and 40 +/- 4% (mean +/- S.D.) of baseline values in the control group and the preconditioned group, respectively (P < 0.05). Furthermore, we observed less contracture during epirubicin infusion and more effective reversal of contracture during the recovery period in the preconditioned hearts. Improvement in cardiac function was associated with a significantly lower (P < 0.05) myocardial content of epirubicin in the preconditioned group at the end of the infusion period. We conclude that ischaemic preconditioning attenuates the acute cardiotoxicity of epirubicin, probably by reducing the myocardial accumulation of the anthracycline.

Adenosine Triphosphate↗