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Abstract. Patients diagnosed with acute myeloid leukaemia are often treated with a combination of daunorubicin and 1-ß-D-arabinofuranosylcytosine (ara-C). Both daunorubicin and ara-C exert their effects in the cell nucleus but by different mechanisms, i.e. daunorubicin causes double stranded DNA breaks by inhibition of the nuclear enzyme, topoisomerase (topo) II·, whereas ara-C is an anti-metabolite that integrates with DNA during DNA synthesis and causes cell cycle arrest. Despite the initial efficacy of these drugs, resistance often develops in the clinical setting. The mechanisms underlying clinical resistance to these drugs are poorly understood, but may be associated with an increase in the proportion of topo II· negative cells. Therefore, the aim of this study was to determine whether daunorubicin treatment results in increased numbers of topo II· negative subpopulations in vitro. Acute myeloid leukaemia cells isolated from 12 consenting patients were treated for 24 h with increasing concentrations of daunorubicin or ara-C and the proportion of topo II·-negative cells in surviving cell populations determined by flow cytometry. Treatment with daunorubicin, but not ara-C, resulted in a significant increase in the proportion of topo II· negative cells (p=0.0023). These results suggest that daunorubicin may act by cell cycle arrest and/or by selection of pre-existing topo II· negative subpopulations. Both of these mechanisms can theoretically contribute to a reduced efficacy of a second dose of daunorubicin. The clinical relevance of these interactions should be further elucidated in experimental and clinical studies. IntroductionA combination of daunorubicin and 1-ß-D-arabinofuranosylcytosine (ara-C) is the standard induction treatment for acute myeloid leukaemia (AML) (1). Daunorubicin exerts its effect in the cell nucleus by interaction with DNA and the enzyme, topoisomerase (topo) II·. Ara-C is a nucleoside analogue that requires phosphorylation to ara-CTP to become an active cytotoxic drug (2). Similarly to daunorubicin, ara-C exerts its effect in the cell nucleus and causes DNA damage by incorporation into the DNA molecule (3). Unfortunately, only 50-60% of patients treated with cytostatic drugs such as daunorubicin and ara-C will enter complete remission, and the long-term survival rate is only 10-20% (1). A major reason for this poor outcome is believed to be a result of intrinsic or acquired resistance to cytostatic drugs.Several cellular mechanisms have been identified that are involved in drug resistance. One mechanism that may play a key role in resistance to daunorubicin is expression of the target molecule, topo II·. Topo II· changes the tertiary structure of DNA and plays an essential role during transcription and duplication of DNA (4). To act as a functional enzyme it requires dimerisation, mainly in the form of homodimerisation. The topo II· dimer causes DNA double-strand breaks that are fixed by disulphide bonds, the so-called cleavable complex. Under ATP hydrolysis the DNA break is religate...

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Improving the ability of teachers in making teaching aids through academic supervision at the private junior high school, Gema Bukit Barisan, Tanjung Morawa sub-district. In the educational philosophy of Ki Hajar Dewantara, Ing Ngarso Sung Tulodo, Ing Madya Mangun Karso, Tut Wuri Handayani, it means that learning is student-centered. However, until now, the learning that takes place in the research-assisted schools is more teacher-centered. This is because the teacher still does not want to take the time to make teaching preparations. The time of the research is carried out in semester 1 of the 2021/2022 academic year starting the first week of October and ending in the fourth week of December. The research was carried out in one of the schools that was supervised by the supervisor, namely the Gema Bukit Barisan Private Junior High School Tanjung Morawa. Indicators of success in this study are (1) increasing the ability of teachers in making teaching aids, (2) increasing student motivation in learning. From the supervision I did to the three teachers at the private SMP, Gema Bukit Barisan, Tanjung Morawa District, they have begun to understand how important it is to make teaching aids in learning activities in the classroom. Previously, they had never made or used teaching aids. With my direction and guidance, they understand and can use it according to the subject or material that is understood.

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