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Context: The molecular mechanism of doxorubicin (DOX) cardiotoxicity involves overproduction of free radicals that leads to intracellular calcium dysregulation and apoptosis. Mangiferin (MGR), a naturally occurring glucosylxanthone, has antioxidant and cardioprotective properties. However, its cardioprotection mechanism has yet to be revealed. Objective: This study determines whether the cardioprotective effect of MGR is caused by its effect on intracellular calcium regulation. Materials and methods: Male Sprague-Dawley rats were induced by DOX intraperitoneally with a total dose of 15 mg/kg bw. MGR was given orally at the doses of 30 and 60 mg/kg bw/d for seven consecutive weeks. The parameters examined were mRNA expression levels of proinflammatory cytokine gene (TNF-a), calcium regulatory gene (SERCA2a) and proapoptotic genes (caspase-9 and caspase-12), as well as cytosolic and mitochondrial calcium levels. Results: Treatment with MGR at 60 mg/kg bw/d significantly decreased the mRNA expression levels of TNF-a by 44.55% and caspase-9 by 52.79%, as well as the cytosolic calcium level by 24.15% (p50.05). SERCA2a and caspase-12 expressions were only slightly affected (27.27% increase and 24.85% decrease for SERCA2a and caspase-12, respectively, p40.05). Meanwhile, MGR 30 mg/kg bw/d gave insignificant results in all parameters. Discussion and conclusion: MGR protected against DOX-induced cardiac inflammation and apoptosis via down-regulation of proapoptotic and proinflammatory gene expressions, upregulation of SERCA2a gene expression, and normalization of cytosolic calcium level. Thus, the cardioprotective effect of MGR is at least in part due to the regulation of intracellular calcium homeostasis. ARTICLE HISTORY

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Tujuan untuk meninjau efi kasi dan keamanan terapi diabetes melitus tipe 2 berbasis inkretin (incretin-based therapy) yang saat ini beredar (eksenatid, liraglutid, sitagliptin, vildagliptin) pada populasi Asia. Metode Kami melakukan pencarian data uji klinik acak yang relevan pada MEDLINE mengenai terapi berbasis inkretin pada diabetes mellitus tipe 2 populasi Asia. Data yang digunakan adalah data efi kasi dan keamanan GLP-1 (glucagon-like peptide-1) mimetik dan penghambat DPP-4 (dypeptidyl peptidase-4). Hasil Empat belas uji klinik acak terapi berbasis inkretin yang mengikutsertakan 3567 pasien diabetes melitus tipe 2 pada populasi Asia (Jepang, Cina, Korea, India). Terapi berbasis inkretin memperbaiki HbA1c lebih besar (hingga-1,42% pada eksenatid 10 mcg bid,-1,85% pada liraglutid 0,9 mg qd,-1,4% pada sitagliptin 100 mg dan-1,4% pada vildagliptin 50 mg bid) dibandingkan dengan yang ditemukan pada uji klinik populasi Kaukasia, dengan profi l keamanan yang setara. Kesimpulan Efi kasi terapi berbasis inkretin pada populasi Asia memperbaiki parameter glikemik lebih besar pada beberapa parameter glikemik dibandingkan dengan pada populasi Kaukasia. Hasil ini mengindikasikan bahwa terapi berbasis inkretin lebih efektif pada populasi Asia dibandingkan dengan populasi Kaukasia.

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Background: Dual antiplatelet therapy (DAPT) using either an aspirin–clopidogrel (A–C) combination or aspirin–ticagrelor (A–T) combination has become the standard therapy for acute coronary syndrome (ACS). Ticagrelor shows better pharmacokinetic profiles but is more expensive. This study aimed to compare cost-effectiveness and safety profiles of A–C versus A–T in patients with ACS.Methods: This was a retrospective cohort study of ACS patient at the Cipto Mangunkusumo Hospital between 2014 and 2016. ACS patients treated for the first time with A–T or A–C were included. Occurrence of major adverse cardiovascular events (MACE) within 3, 6, 9, and 12 months were used as effectiveness outcomes, while safety outcomes were measured based on the incidence of adverse drug reactions (major and minor bleeding, dyspnea, and hyperuricemia). Cost-effectiveness analysis was presented as incremental cost-effectiveness ratio (ICER).Results: Data records obtained from 123 ACS patients treated with A–C and 57 ACS patients treated with A–T were evaluated. Within the first three months, the MACE rate was 15.8% in the A–T group and 31.7% in the A–C group (RR: 0.498, 95% CI: 0.259–0.957, p=0.039). There was no statistically significant difference observed in the number of MACE between groups after 6, 9, and 12 months. The A–T group had a higher incidence of major bleeding (melena) than the A–C group (5.3% vs 1.62%, p=0.681), especially in geriatric patients. Minor bleeding was observed in three patients of the A–C group, but in none of the patients in the A–T group. The cost of ICER was IDR 279,438, indicating the additional cost needed for avoiding MACE within 3 months, if A–T was used.Conclusion: The aspirin–ticagrelor combination is a clinically superior and cost-effective option for MACE prevention among ACS patients, especially during the first three months of DAPT, with a slight but not significantly higher major bleeding risk when compared to the aspirin–clopidogrel combination.

ABSTRAK ABSTRACTBackground: Epithelial mesenchymal transition (EMT) plays a significant role in the development of cancer cell resistance to drugs. Vimentin, a type III intermediate filament protein, is a marker of EMT. Vimentin's overexpression in cancer correlates well with increased tumor growth, change in cell shape and poor prognosis. Endoxifen is an active metabolite of tamoxifen and has become a new potent agent in the treatment of breast cancer. This is a study that aimed to investigate the effect of endoxifen exposure with or without estradiol on cell viability, cell morphology and EMT progression through the analysis of vimentin mRNA expression after 4-week treatment.