Hasil Pencarian  ::  Simpan CSV :: Kembali

"Latar Belakang: Cisplatin adalah obat antineoplastik berbasis platinum yang dipakai untuk berbagai jenis kanker. Walaupun memiliki efikasi yang tinggi, cisplatin memiliki efek samping yang berbahaya, yaitu gagal ginjal akut yang disebabkan oleh stres oksidatif dan inflamasi. Kurkumin diketahui memiliki efek antioksidatif dan antiinflamasi pada gagal ginjal akut yang disebabkan oleh cisplatin, walaupun memiliki bioavailabilitas yang rendah. Hal ini dapat diatasi dengan menggunakan nanokurkumin. Penelitian ini bertujuan untuk membandingkan efektivitas kurkumin dan nanokurkumin dalam melindungi ginjal akibat pemberian dosis tunggal cisplatin, terutama pada ekspresi Nrf2 dan Keap1: Tikus Sprague-dawley jantan (n=25) dikelompokkan menjadi 5 kelompok (Kontrol, cisplatin, cisplatin + curcumin, cisplatin + nanokurkumin 50 mg/kgBB/hari, cisplatin + nanokurkumin 100mg/kgBB/hari, dan dikorbankan 9 hari setelah perlakuan. Sampel ginjal diambil dan dilakukan RT-PCR untuk Nrf2 dan Keap1 Hasil: Pemeriksaan ekspresi gen Nrf2 ditemukan tidak terdapat hubungan yang signifikan antarkelompok (p>0.05). Namun, pada pemeriksaan ekspresi gen Keap1, terlihat ekspresinya lebih tinggi pada tikus yang mendapatkan cisplatin dibandingkan kelompok normal dan ekspresi gen Keap1 juga terlihat lebih tinggi pada kelompok dengan 100mg nanokurkuminKesimpulan Nanokurkumin dapat meningkatkan ekpresi Keap1, walaupun tidak signifikan secara statistik. Hal ini dapat disebabkan oleh karena peningkatan aktivasi Nrf2 yang menyebabkan umpan balik negatif sehingga menurunkan ekspresi Keap1 Background: Cisplatin is a platinum-based drug that is used for various type of cancer. Despite its high efficacy, cisplatin has a very destructive side effect, which is acute kidney failure due to oxidative stress and inflammation. Curcumin has been shown to possess anti-oxidative and anti-inflammatory effect in cisplatin-induced AKI, despite its poor bioavailability, which can be managed by administering nanocurcumin. This study aims to compare the effectivity of curcumin and nanocurcumin in protecting kidney doe to single-dose cisplatin administration, especially in the antioxidative gene Nrf2 and its inhibitor Keap1 Method: Male Sprague-Dawley rat (n=25) are divided into 5 groups (Control, Cisplatin, Cisplatin + Curcumin, Cisplatin + Nanocurcumin 50mg/kgBW, Cisplatin + Nanocurcumin 100mg/kgBW) and sacrificed 9 days after treatment. Kidney sample is taken and RT-PCR for Nrf2 and Keap1 is done.Results: Result of RT-PCR shows no statistical significance in Nrf2 expression across the group (p>0.05). However, Keap1 level was increased in rats treated with 100mg Nanocurcumin. Conculsion: that nanocurcumin can increase Keap1 level but not significantly. This might be caused by increased Nrf2 activation which induce negative feedback thus increasing Keap1 transcription level."

"ABSTRAKLatar belakang: Sepsis merupakan masalah kesehatan penting yang dapat menyebabkan insidens kematian sampai 50% pada pasien dengan sepsis berat. Antibiotik aminoglikosidaterutama amikasin semakin banyak digunakan untuk mengobati infeksi kuman Gram negatif pada pasien sepsis di ICU, meskipun penggunaan obat tersebut pada dosisterapi dapat meningkatkan risiko kerusakan ginjal sekitar 10-25%. Pemantauan kadar lembah amikasin serta biomarker dini diperlukan untuk mencegah kerusakan ginjal pada pasien sepsis yang dirawat di ICU. Penelitian ini dilakukan untuk mengetahui hubungan kadar lembah amikasin pada pasien ICU dewasa yang dirawat di Rumah Sakit Cipto Mangunkusumo yang diberikan amikasin 1000 mg/hari denganpeningkatan kadar KIM-1 normalisasi dalam urin yang merupakan biomarker dini nefrotoksisitas.Metode:Penelitian ini merupakan penelitian pendahuluan yang dilakukan pada 12 pasien sepsis dewasa yang dirawat di ICU RSCM dan diberikan amikasin 1000 mg/hari pada bulan Mei-September 2015. Kadar lembah amikasin dosis ketiga dihubungkan dengan peningkatan kadar KIM-1 normalisasi yang diukur melalui urin 24 jam setelah pemberian amikasin dosis pertama/kedua dan dosis ketiga.Hasil:Dari 12 subyek penelitian, didapatkan 3 subyek penelitian dengan kadar lembah amikasin di atas 10 g/mL, sedangkan 9 subyek penelitian kadar lembahnya ada dalam batas aman (di bawah 10 g/mL). Delapan dari 12 subyek penelitian (66,7%) mengalami peningkatan kadar KIM-1 normalisasi dalam urin hari ketiga dibandingkan hari pertama. Tidak ada hubungan antara kadar lembah amikasin dengan peningkatan kadar KIM-1 normalisasi dalam urin (p=0,16; r=0,43).Kesimpulan:Pasien sepsis yang mendapat amikasin 1000 mg/hari di ICU RSCM selama 3 hari memperlihatkan kadar lembah amikasin plasma dalam batas aman untuk ginjal.

---

ABSTRACT

Background: Sepsis is a common caused of mortality which may account for up to 50% death rate in patients with severe sepsis. Aminoglycoside antibiotics, especially amikacin, are the most commonly used antibiotics in the septic patients with Gram-negative bacterial infections, despite these drugs may induce nephrotoxicity in 10-25%

patients. Hence, it is essential to monitor amikacin trough plasma concentration and to detect nephrotoxicity as early as possible. The aim of this study is to find out the correlation between amikacin trough plasma concentration with normalized KIM-1 concentration in the urine as a sensitive and specific biomarker.

Methods:

This is a pilot study conducted in 12 septic patients treated with amikacin 1000 mg/day from May, 2015 to September, 2015. The correlation between amikacin

trough plasma concentrations measured at the third doses with the elevation of urine normalized KIM-1 concentrations measured at the first/second and the third doses were evaluated.

Results:

We observed 3 patients with amikacin trough plasma concentration above the safe level (>10 g/mL), while 9 patients had amikacin concentrations within the safe

plasma level (<10 g/mL). Furthermore, we observed 8 out of 12 patients with higher normalized KIM-1 concentrations measured at third doses compared to normalized KIM-1 concentrations measured at first/second doses. There was no correlation between amikacin trough concentration with elevated urine normalized KIM-1

concentration (p=0,16; r=0,43).

Conclusion:

Septic patients treated with amikacin 1000 mg/day hospitalized in ICU RSCM for 3 days have amikacin safe trough plasma concentration."

"ABSTRAKLatar Belakang: Endoksifen merupakan terapi baru pada pengobatan sel kanker payudara yang responsif terhadap endokrin. Studi terdahulu menunjukkan bahwa paparan endoksifen jangka panjang dapat menyebabkan resistensi melalui mekanisme Epithelial-Mesenchymal Transition (EMT). EMT adalah sebuah proses dimana suatu sel epithelial berubah menjadi sel mesenkimal. Proses EMT ditandai dengan adanya modulasi marker-marker epitelial seperti E-cadherin, vimentin dan TGF-β1. Berbagai penelitian telah menunjukan bahwa paparan singkat kurkumin dapat memperbaiki marker-marker EMT. Namun, kurkumin memiliki keterbatasan karena bioavailabilitasnya yang rendah. Oleh karena itu, pada penelitian ini kami menggunakan nanokurkumin untuk mencegah jalur EMT.Metode: ini merupakan penelitian in vitro menggunakan sel MCF-7. Kami membagi sel menjadi beberapa kelompok yaitu: Endoksifen 1000 nM+β-estradiol 1 nM, Endoksifen 1000 nM+β-estradiol 1 nM + nanokurkumin (8.5 μM dan 17 μM), Endoksifen 1000 nM+β-estradiol 1 nM+kurkumin 17 μM dan DMSO selama 8 minggu. Sel kemudian dipanen dan dihitung setiap minggu. Setelah minggu ke-4 dan ke-8 paparan, ekspresi E-cadherin, TGFβ1 dan vimentin diukur menggunakan two-step qRT PCR. Pada minggu ke-8, kadar protein TGF-β1 diukur dengan ELISA, sementara morfologi sel MCF-7 diamati menggunakan mikroskop konfokal.Hasil: Terdapat peningkatan viabilitas sel pada kelompok Endoksifen 1000 nM+β-estradiol 1 nM. Viabilitas sel menurun secara signifikan pada kelompok nanokurkumin dan kurkumin 17 μM, tetapi tidak pada kelompok nanokurkumin 8.5 μM. Analisis marker EMT pada minggu ke-8 menunjukkan terdapat peningkatan ekspresi mRNA vimentin dan TGF-β1 sementara ekspresi mRNA E-cadherin dan kadar protein TGF-β1 tampak menurun. Hasil menunjukkan bahwa pemberian nanokurkumin pada semua dosis tidak mampu memperbaiki ekspresi vimentin, TGF-β1, dan E-cadherin. Tidak tampak perbedaan yang signifikan antara nanokurkumin dan kurkumin terhadap modulasi marker-marker EMT pada sel kanker payudara yang dipaparkan endoksifen berulang. Pengamatan morfologi menggunakan mikroskop konfokal menunjukkan adanya sel mesenkimal baik pada kelompok endoksifen+β-estradiol maupun kelompok yang mendapat nanokurkumin/kurkumin.Kesimpulan: nanokurkumin tidak mampu mencegah aktivasi EMT walaupun dapat menurunkan viabilitas sel pada penggunaan jangka panjang. Meskipun nanokurkumin lebih terakumulasi di dalam sel. tidak tampak perbedaan potensi dibandingkan dengan kurkumin dalam menurunkan marker EMT.

---

ABSTRACT

Background: Endoxifen is a novel therapy in the treatment of endocrine responsive type of breast cancer. Previous study showed that long-term exposure of endoxifen may lead to resistance through the mechanism of Epithelial-Mesenchymal Transition (EMT). EMT is a process where epithelial cells turn into mesenchymal cells. EMT is characterized by the modulation of epithelial markers such as E-cadherin, vimentin and TGF-β. Various studies have shown that short term treatment with curcumin may improve EMT markers. However, the efficacy of curcumin is limited by its low bioavailability. In this study, we use nanocurcumin to prevent the activation of EMT.

Methods: This is an in vitro study in MCF-7. We exposed the cells to several groups, which are: endoxifen 1000nM + β-estradiol 1 nM, endoxifen 1000nM + β-estradiol 1 nM + nanocurcumin (8.5 μM and 17 μM), endoxifen 1000nM + β-estradiol 1 nM + curcumin 17 μM and DMSO, for 8 consecutive weeks. Cells were then harvested and counted weekly. After 4 and 8 weeks of treatments, E-cadherin, TGF-β and vimentin expressions were measured using a two-step qRT PCR. At week 8, protein level of TGF-β1 was measured by ELISA, while MCF-7 cell morphology was observed using confocal microscope.

Results: MCF-7 cell viability was increased in endoxifen + β-estradiol group. Cell viability was significantly decreased in nanocurcumin and curcumin 17 μM, but not in nanocurcumin 8.5 μM group. Analysis of EMT markers at week 8 indicates that there were increase in vimentin and TGF-β mRNA expressions, while E-cadherin mRNA expressions and TGF-β1 protein concentrations were shown to decrease. The results showed that administration of nanocurcumin in all the dose administered were incapable improving the expressions of vimentin, TGF-β1 and E-cadherin. There were no significant differences between nanocurcumin and curcumin on the modulation of EMT?s markers in breast cancer cells exposed to repeated endoxifen and estradiol. Morphological observation using confocal microscope showed the presence of mesenchymal cells both in the endoxifen+β-estradiol group and the group given nanocurcumin/curcumin.

Conclusion: nanocurcumin is incapable to prevent the activation of EMT, although it may reduce cell viability on a long-term use. Although nanocurcumin are more accumulated in the cells, they show no difference in efficacy compared with curcumin in reducing EMT markers."

"Nefrotoksisitas merupakan efek samping utama yang membatasi penggunaan cisplatin sebagai obat anti-tumor. Kurkumin memeliki beberapa aktivitas farmakologis salah satunya, yaitu sebagai nefroprotektor. Akan tetapi kurkumin kurang larut di dalam air, sehingga digunakan nanokurkumin yang lebih mudah larut/terdispersi dalam air. Tujuan penelitian ini adalah untuk mengetahui efek kurkumin dan nanokurkumin terhadap nefrotoksisitas tikus yang diinduksi cisplatin melalui jalur ERK1/2. Perlakuan hewan coba dilakukan selama 10 hari, menggunakan tikus Sprague Dawley yang dibagi menjadi 5 kelompok, n=6, yaitu kelompok normal, cisplatin CIS, Cisplatin kurkumin 100 mg/kgBB/hari p.o Cis Kurku100, Cisplatin nanokurkumin 50 mg/kgBB/hari p.o Cis Nanokur50, Cisplatin nanokurkumin 100 mg/kgBB/hari p.o Cis Nanokur100 . Pada hari ke-7 dilakukan injeksi cisplatin 7 mg/kgBB, i.p dan 72 jam setelah injeksi cisplatin dilakukan pengambilan darah dan organ ginjal. Cisplatin dosis tunggal pada kelompok CIS menyebabkan peningkatan kadar BUN dan kreatinin dalam plasma, kadar MDA, peningkatan rasio ekspresi BCL-2/Bax, serta peningkatan rasio ekspresi protein p-ERK/ERK secara signifikan, dibandingkan kelompok normal. Pemberian kurkumin 100 mg/kgBB dan nanokurkumin 100 mg/kgBB berperan sebagai antioksidan untuk mencegah progresifitas nefrotoksisitas akibat cisplatin, dilihat melalui terjadinya penurunan kadar BUN dan kreatinin dalam plasma, penurunan kadar MDA, dan peningkatan rasio ekspresi gen BCL-2/Bax secara signifikan dibandingkan kelompok CIS, serta penurunan rasio ekspresi protein p-ERK/ERK secara signifikan dibandingkan kelompok CIS. Cisplatin dosis tunggal 7 mg/kgBB dapat menyebabkan nefrotoksisitas pada tikus yang menyerupai AKI Acute Kidney Injury pada manusia. Kurkumin 100 mg/kgBB cenderung memiliki efek nefroprotektor yang lebih baik dalam mencegah progresifitas nefrotoksisitas akibat cisplatin melalui jalur stress oksidatif dan apoptosis.

---

Nephrotoxicity is the major limitation for the clinical use of cisplatin as an antitumor. Curcumin has some pharmacological activity, one of them as nephroprotector. However, curcumin less soluble in water, so it is used nanocurcumin which is readily dispersed in aqueous media. The purpose of this study is to investigate the effects of curcumin and nanocurcumin against ciplatin induced nephrotoxicity in rats through ERK1 2 pathway. This study conducted for 10 days treatment, five groups n 6 of male Sprague Dawley rats were examined normal, cisplatin CIS 7 mg kgBW, Cis curcumin Cis Curcu100 100 mg kg BW day, Cisplatin nanocurcumin 50 mg kg BW day Cis Nanocur50, and Cisplatin nanocurcumin 100mg kg BW day Cis Nanocur100 . After 72 h following injection cisplatin, specimens were collected. This study resulted a single dose of cisplatin in CIS group caused a significant increased in plasma BUN, plasma creatinine, MDA levels, decreased ratio expression of BCL 2 Bax gene, and increased ratio of p ERK ERK as compared to normal group. Pre treatment with curcumin 100 mg kgBW and nanocurcumin 50 and 100 mg kgBW acts as an antioxidant to prevent progression of nephrotoxicity cisplatin, were reduced plasma BUN levels, plasma creatinine levels, MDA levels in kidney, increased GSH level in kidney, increased ratio expression of BCL 2 Bax gene in kidney, and decreased ratio of p ERK ERK protein in kidney compared with cisplatin induced nephrotoxicity rats without treatment. Cisplatin with single dose 7 mg kgBW is able to induced nephrotoxicity in rats that mimicked acute kidney injury in human. Curcumin 100 mg kgBW tend to have a better nephroprotector effect in preventing the progression of cisplatin induced nephrotoxicity through oxidative stress pathways and apoptosis. "