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"Filariasis limfatik adalah penyakit tular vektor yang disebabkan oleh 3 spesies cacing filaria yaitu Wuchereria bancrofti, Brugia malayi, dan Brugia timari. Fiiariasis ditargetkan untuk dieliminasi pada tahun 2020 oleh WHO dengan merekomendasikan pengobatan masal (MDA) dengan dosis tunggal kombinasi DEC 6 mg/kg berat badan + ALB 400 mg, selama 5 - 10 tahun. Teknik diagnostik yang digunakan adalah pemeriksaan mikroiilaria pada sediaan darah malam, namun teknik ini memiliki banyak kekurangan, sehingga perlu digunakan metode diagnosis lain, serologi, untuk memantau program eliminasi filariasis. Diagnosis serologi dengan antigen rekombinan B.malayi Bml4, mendeteksi antibodi IgG4 antifilaria. Penelitian ini dilakukan untuk mengetahui hubungan penurunan prevalensi mikrofiiaria berdasarkan mikroskopis dengan penurunan respon antibodi IgG4 antifilaria berdasaxkan uji ELISA dengan antigen rekombinan Bml4 sebelum dan sesudah pengobatan masal, serta melihat sensitivitas dan spesitisitas antigen rekombinan Bml4 sebagai alat diagnosis baru untuk memantau pengobatan masal filariasis. Studi longitudinal dilakukan di daerah endemik filariasis B. timori di Kabupaten Alor, Nusa Tenggara Timur. Pengukuran kadar lgG4 anti tilaria menggunakan ELISA-Bml4 dibandingkan dengan pemeriksaan mikroskopik untuk dilihat sensitivitas dan spesiiisitasnya. Kemudian dilihat pola penurunan kadar IgG4nya terhadap teknik mikroskop selama pengobatan 5 tahun. Dari 51 sampel serum yang diperiksa, didapatkan hasil sensitifitas (94%) dan Nilai Duga Negatif (NDN) yang tinggi 88% (p=0.000). Dengan intervensi pcngobatan dapat menurunkan kadar IgG4 antifilaria yang bermakna pada kelompok Mf+ELISA+ (True positw dan Mf-ELISA+ (False Positf), sehingga uji diagnostik serologi menggunakan ELISA-Bm14 dapat digunakan untuk menentukan keberhasilan program pemberantasan filariasis di Indonesia.

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Lymphatic iilariasis is a disease transmitted by mosquito vectors which is caused by 3 spesies of tilarial worms, Wuchereria bancrojli, Brugia maiayi, and Brugia limori. Filariasis has been targetted to be eliminated by WHO in the year of 2020 using mass drug treatment in population with combination drugs of DEC 6 mg/kg body weight plus Albendazole 400 mg for 5 - 10 years.

Diagnostic tool used in the program is microscopic examination of night blood samples however there are some constraints. Ti1?I¢f0l?C, other diagnostic tools such as serological assay has to be used in monitoring the filariasis elimination program. Serological diagnosis using recombinant antigen B. malayi Bm14 has been developed to detect IgG4 antibody anti tilaria. The purpose of this study is to determine the decrease of iilariasis prevalence detected by two different diagnostic tools, microscopic examination for microfilariac and ELISA using Bml4 recombinant antigen for IgG4 antibody before and after mass treatment and the comparison between the two diagnostic tools in terms of Sensitivity and specificity.

A longitudinal study is done in B. timori endemic area in Alor district, Nusa Tenggara Timur. Measurement of IgG4 anti filaria titer using ELISA-Bm] 4 is compared to microscopic examination to detect microfilariae in determining the infected persons. The decrease of IgG4 titer as well as microtilarial counts are also observed during 5 years mass treatment. A total of 51 sera samples was examined by microscopic and ELISA showing sensitivity is (94%) and negative predictive value is also high, 88% (p~#0.000). After intervention with mass treatment, the titer of IgG4 decreased significanlty in Mf+E,LISA+ (True Parity) group as well as Mf-ELISA-+ (False Parity) gmup. The result indicates that serological method, ELISA-Bml4, can be used to dctemiine the progress of the filariasis elimination program in Indonesia."

"Latar belakang. Doksorubisin dikenal sebagai antikanker yang sangat poten, namun penggunaanya dibatasi oleh toksisitas terhadap berbagai organ vital, salah satunya jantung. Mekanisme molekuler kardiotoksisitas doksorubisin berhubungan dengan produksi radikal bebas berlebih yang menyebabkan penurunan ekspresi gen-gen yang mengkode protein regulator kalsium intrasel sehingga terjadi gangguan homeostasis kalsium intrasel yang menyebabkan aktivasi jalur apoptosis intrinsik yang dimediasi caspase, terutama caspase-9 dan caspase-12. Stres oksidatif akibat DOX juga menyebabkan peningkatan produksi sitokin proinflamasi yang berperan dalam terjadinya apoptosis. Mangiferin merupakan salah satu kandidat potensial senyawa kardioprotektor untuk terapi doksorubisin, akan tetapi mekanisme molekulernya belum diketahui dengan pasti. Penelitian ini bertujuan untuk mengetahui apakah mekanisme molekuler mangiferin berhubungan dengan regulasi kalsium intraseluler. Metode. Penelitian dilakukan terhadap tikus Sprague Dawley jantan yang diinduksi doksorubisin dengan dosis total 15 mg/kg BB. Pemberian mangiferin dilakukan dengan dosis 30 dan 60 mg/kg BB secara oral selama tujuh minggu. Parameter yang diamati adalah ekspresi protein regulator Ca2+ intrasel yaitu SERCA2a, parameter apoptosis (caspase-12 dan caspase-9), kadar kalsium sitosol dan mitokondria, serta parameter inflamasi (TNF-α). Hasil. Induksi doksorubisin menyebabkan penurunan ekspresi SERCA2a, disertai peningkatan ekspresi gen pro-apoptosis yakni caspase-12 dan caspase-9 serta peningkatan derjat inflamasi dan kerusakan jantung. Pemberian mangiferin menyebabkan peningkatan ekspresi SERCA2a, penurunan ekspresi caspase-12 dan caspase-9 serta penurunan derajat inflamasi. Kesimpulan. Berdasarkan hasil tersebut, dapat disimpulkan bahwa normalisasi homeostasis kadar kalsium intrasel merupakan bagian dari mekanisme kardioproteksi mangiferin.

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Background. Doxorubicin is well known as a potent anticancer agent despite its toxicity on various vital organs, especially the heart. The molecular mechanism of doxorubicin cardiotoxicity revolves around the overproduction of free radicals which cause downregulation of genes encoding calcium regulatory proteins, leading to disturbance of calcium homeostasis and activation of intrinsic apoptotic pathway mediated by caspases, particularly caspase-12 and caspase-9. Doxorubicin cardiotoxicity is also accompanied by inflammation that is crucial for apoptosis. Mangiferin is currently studied as cardioprotective agents for doxorubicin therapy. However, its molecular mechanism has yet been revealed. This study was aimed to determine whether cardioprotective effect of mangiferin is caused by its effect on intracellular calcium regulation.

Method. Male Sprague Dawley rats were induced by doxorubicin with a total dose of 15 mg/kg BW. Mangiferin was given orally at the dose of 30 and 60mg/kg BW for seven weeks. The parameters examined were mRNA expressions levels of calcium regulatory gene (SERCA2a), proapoptotic genes (caspase-9 and caspase-12) and proinflammatory cytokine gene (TNF-α), as well as mitochondrial and cytosolic calcium levels.

Result. It was found that doxorubicin caused downregulation of SERCA2a expression and increased the expression of both proapoptotic genes. Interestingly, we found that mangiferin could attenuate those things above by increasing SERCA2a expression as well as decreasing caspase-9 and caspase-12 expressions, while ameliorating inflammation.

Conclusion. Based on this finding, we suggest that the cardioprotective effect of mangiferin is at least in part due to the regulation of intracellular calcium homeostasis."

"Latar belakang: Mahkota dewa (Phaleria macrocarpa) merupakan salah satu tanaman herbal di Indonesia dan ekstrak air buah mahkota dewa telah terbukti memiliki efek hepatoprotektif. Penelitian ini bertujuan untuk mengetahui aktivitas dan mekanisme kerja ekstrak air buah mahkota dewa dalam mencegah terjadinya fibrosis hati.Metode: Penelitian dilakukan pada tikus Sprague-Dawley jantan yang diinduksi karbon tetraklorida (CCl4) secara intraperitoneal setiap 3 hari sekali selama 8 minggu. Hewan coba dibagi menjadi 6 kelompok: normal, CCl4, n-Acetyl cysteine (NAC) dosis 150 mg/kgBB, ekstrak air buah mahkota dewa dosis 50, 100 dan 150 mg/kgBB. Penilaian dilakukan terhadap parameter aspartat aminotransferase (AST), alanin aminotransferase (ALT), alkali fosfatase (ALP), histopatologi hati, kadar malondialdehid (MDA), rasio GSH/GSSG, kadar Tumor Necrosis Factor (TNF)-α dan kadar Transforming Growth Factor (TGF)-β1Hasil: Hasil studi menunjukkan bahwa ekstrak air buah mahkota dewa dan NAC secara bermakna dapat melindungi hati dari cedera melalui penurunan aktivitas enzim ALT, AST, ALP dan penurunan persentase jaringan ikat pada pemeriksaan histopatologi. Ekstrak air buah mahkota dewa dan NAC dapat menghambat stress oksidatif melalui penurunan kadar MDA hati dan peningkatan rasio GSH/GSSG hati. Ekstrak air buah mahkota dewa dan NAC dapat menekan inflamasi melalui penurunan kadar TNF-α dan menghambat aktivasi sel stelata hati (HSC) yang ditandai dengan penurunan kadar TGF-β1.Kesimpulan: Ekstrak air buah mahkota dewa dapat mencegah fibrosis hati pada tikus yang diinduksi CCl4. Pencegahan terhadap fibrosis tersebut terutama melalui aktivitas antioksidan dan kemampuan menekan sitokin inflamasi TNF-α, serta menghambat aktivasi HSC melalui penurunan sitokin fibrogenik TGF-β1.

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Introduction: Mahkota dewa (Phaleria macrocarpa) is one of the Indonesian herbal plants. Hepatoprotective effect of aqueous extract of mahkota dewa fruits have been studied previously. This study was conducted to evaluate the activity of water extract of mahkota dewa in the prevention of liver fibrosis and its mechanism of action.Method: Male Sprague-Dawley rats were induced by carbon tertrachloride (CCl4) given every 3 days by intraperitoneal injection for 8 weeks. Rats were randomly allocated into 6 groups: control group, n-acetyl cysteine/NAC (150 mg/kgBB), aqueous extract of mahkota dewa (50, 100 and 150 mg/kgBB). Aspartate aminotransaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), liver histopathology, malondialdehyde (MDA), ratio GSH/GSSG, Tumor Necrosis Factor (TNF)-α and Transforming Growth Factor (TGF)-β1 were examined.Results: This study demonstrates that aqueous extract of mahkota dewa and NAC significantly protects the liver from injury by reducing the activity of AST, ALT, ALP and by reducing fibrosis percentage in histopatological examination. Aqueous extract of mahkota dewa and NAC attenuates oxidative stress by reducing the levels of MDA and increasing GSH/GSSG ratio. Aqueous extract of mahkota dewa and NAC suppresses inflammation by reducing the levels of TNF- α and inhibits hepatic stellate cells (HSC) activation by reducing the levels of TGF-β1.Conclusions: Aqueous extract of mahkota dewa prevents CCl4-induced fibrosis in rats. The prevention of liver fibrosis most possibly through its antioxidant activities, suppression of inflammatory cytokines TNF-α and inhibition of HSC activation by reducing fibrogenic cytokines TGF-β1."

"Latar Belakang: Prevalensi hipertensi yang terkait dengan kelainan metabolik semakin meningkat. Penelitian sebelumnya menunjukkan terdapat keterkaitan antara inflamasi yang melibatkan TNF-α sebagai sitokin pro-inflamasi dengan hipertensi dan sindrom metabolik melalui stimulasi angiotensinogen. Penggunaan bahan yang berasal dari alam telah banyak diteliti sebagai alternatif obat hipertensi yang ada saat ini, Salah satunya adalah mangiferin (Mangifera indica Linn.) yang telah diketahui memiliki aktivitas antiinflamasi. Penelitian ini bertujuan untuk menganalisis efek mangiferin terhadap tekanan darah dan perubahan morfologi miokardium serta ekspresi mRNA dan kadar TNF-α di jantung, pada tikus yang diinduksi dengan diit tinggi fruktosa.Metode: Tikus jantan galur Sprague-Dawley, dibagi dalam 2 kelompok yaitu kelompok normal yang hanya diberi diit standar dan kelompok yang diberi diit standar disertai diit tinggi fruktosa. Induksi diit tinggi fruktosa dilakukan selama 6 minggu, dengan pemberian secara oral 60% fruktosa, dua kali sehari dengan dosis 1 mL per pemberian dan 10% fruktosa dalam air minum ad libitum. Kelompok diit tinggi fruktosa selanjutnya dibagi dalam 4 kelompok dengan pemberian terapi per oral selama 4 minggu sebagai berikut: kelompok pertama, sebagai kontrol negatif diberi carboxymethylcellulose 0,5% 1mL/hari; kelompok kedua diberi terapi mangiferin dosis 50 mg/kgBB/hari; kelompok ketiga diberi terapi mangiferin dosis 100 mg/kgBB/hari; dan kelompok keempat, sebagai kontrol positif diberi candersartan 10 mg/kg BB/hari. Pengukuran tekanan darah dilakukan setelah 6 minggu masa induksi dan setelah 4 minggu masa terapi. Pengukuran kadar trigliserida darah dilakukan sebelum masa induksi, setelah 6 minggu masa induksi dan setelah 4 minggu masa terapi. Pada akhir masa studi, hewan didekapitasi dan organ jantung diambil sebagian untuk pemeriksaan histopatologi dan sebagian sisanya untuk pemeriksaan ekspresi mRNA dan kadar TNF-α. Analisis kadar trigliserida dilakukan pada sampel darah.Hasil: Pemberian mangiferin dosis 50 dan 100 mg/kgBB/hari secara bermakna dapat menurunkan kadar trigliserida, tekanan darah, ekspresi mRNA TNF-α dan cenderung menurunkan kadar TNF-α pada jantung tikus, dibandingkan kelompok kontrol. Pemberian kedua dosis mangiferin secara bermakna juga dapat memperbaiki morfologi miokardium dengan menurunkan respon hipertrofi, dibandingkan dengan kelompok kontrol.Kesimpulan: Mangiferin mempunyai potensi untuk mengatasi hipertensi terkait kelainan metabolik melalui hambatannya terhadap TNF-α yang teraktivasi akibat diit tinggi fruktosa.

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Background: Prevalence of hypertension in metabolic disorder increased. Previous study showed that there were a significant correlation between inflammation that involved TNF-α as pro-inflammation cytokine with hypertension and metabolic syndrome through stimulating angiotensinogen production. Many researches have been conducted on plant-based ingredients as alternative to the current hypertension medicines, such as mangiferin (Mangifera indica Linn.) which is well-known to have antiinflammation property. The aims of the present study is to evaluate the effect of mangiferin on blood pressure, the changes in morphology of myocardium, mRNA expression and level of TNF-α in heart tissue of rat with high fructose diet.Methods: Male Sprague-Dawley rats, divided in 2 groups, i.e., normal group fed with standard diet only and fructose group fed both standard and high-fructose diet. In the duration of 6 weeks, 60% fructose were given by direct oral ingestion, 1 mL twice a day and 10% fructose in drinking water ad libitum. The fructose group then divided further into 4 groups with different 4-week orally treatment. They were given: carboxymethylcellulose 0,5% 1mL/day, mangiferin at the dose of 50 mg/kgBW/day, mangiferin at the dose of 100 mg/kgBW/day, and candersartan at the dose of 10 mg/kg BW/day as positive control, respectively. The blood pressure was measured at the end of 6-week fructoce-induced and at the end of 4-week treatment. At the end of the study, all animals were decapitated. Half of the heart were taken for the histopathological assessment, and the remaining was for mRNA expression and level of TNF-α. The analysis of trigliseride level was conducted on blood samples.Result: The administration of mangiferin decreased the trigliseride level, the blood pressure, the expression of mRNA TNF-α and tends to decrease the level of TNF-α. It also improved the histology changes caused by high fructose diet.Conclusion: Mangiferin has a potency as antihypertension in high fructose rats at least in part related to its antiinflammation effect."

"Latar Belakang: Kardiomiopati uremikum adalah kelainan jantung yang didasari oleh kelainan pada ginjal dan merupakan penyebab kematian tertinggi pada pasien penyakit ginjal kronik (PGK). Overload cairan dan stres oksidatif berperan dalam patogenesis penyakit ini. Kuersetin adalah antioksidan yang bersifat kardioprotektif, namun belum ada data tentang efeknya pada kardiomiopati uremikum. Penelitian ini bertujuan untuk mengetahui efek kuersetin pada kardiomiopati uremikum menggunakan model nefrektomi 5/6 pada tikus. Metode: Uremia diinduksi pada 3 kelompok tikus jantan Sprague-Dawley dengan nefrektomi 5/6, satu kelompok kontrol tanpa nefrektomi 5/6, masing-masing 6 ekor/kelompok dan diamati selama 8 minggu. Kelompok SNX tidak diberi pengobatan. Kelompok SNX+Q mendapat quersetin per oral dengan dosis 100 mg/kgBB/hari dan kelompok SNX+Cap mendapat kaptopril 10 mg/kgBB/hari. Hewan uji dikorbankan untuk diukur kadar malondialdehid (MDA) plasma dan jantung, aktivitas glutation peroksidase (GPX) jantung, NT-proBNP plasma, dan fibrosis jantung. Data dianalisis dengan uji ANOVA. Hasil: Nefrektomi 5/6 menimbulkan sedikit fibrosis jantung, tidak mempengaruhi NT-proBNP, tidak mempengaruhi MDA jantung dan plasma dan meningkatkan secara bermakna aktivitas GPX jantung (p<0.05) sedangkan pemberian kuersetin dan kaptopril tidak mempengaruhi fibrosis jantung, tidak mempengaruhi NT-proBNP (p>0.05), tidak mempengaruhi MDA jantung dan plasma (p>0.05) dan tidak mempengaruhi aktivitas GPX jantung pada tikus uremia yang diinduksi dengan nefrektomi 5/6 (p>0.05). Kesimpulan: Kuersetin tidak mempengaruhi fibrosis jantung dan fungsi jantung tikus uremia pasca nefrektomi 5/6. Peningkatan secara bermakna aktivitas GPX jantung pada semua kelompok pasca nefrektomi 5/6 (p<0.05) dibandingkan kelompok kontrol normal menunjukkan bahwa jantung tikus uremia masih berada pada fase kompensasi, yaitu mekanisme adaptasi jantung dan fungsi jantung belum terganggu meskipun terjadi sedikit fibrosis jantung.

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Background: Uremic cardiomyopathy is a heart disease because of abnormalities in the kidneys that is the leading cause of death in patients with chronic kidney disease (CKD). Fluid overload and oxidative stress play an important role in its pathogenesis. Quercetin, as an antioxidant, has cardioprotective effect. To the best of our knowledge, its effect on uremic cardiomyopathy has not been investigated yet. This study aims to determine the effect of quercetin on uremic cardiomyopathy using 5/6 nephrectomy model in rats.

Methods: Uraemia was induced surgically in male Sprague-Dawley rats via 5/6 nephrectomy (SNX). Quercetin was administered per orally at a dose of 100 mg/kgBW/day for 8 weeks prior to sacrifice. Meanwhile captopril was administered per orally at a dose of 10 mg/kgBW/day. Oxidative stress was assessed using tiobarbituric acid reactive substances reaction then glutathione peroxidase (GPX) activity was determined to study on antioxidant mechanism. Myocardial fibrosis was analyzed using Massons? Trichrome staining and NTproBNP was measured as a marker of cardiac function. Data was analyzed using ANOVA.

Results: Nephrectomy 5/6 had no effects on plasma NT - proBNP, cardiac and plasma MDA, but induced mild myocardial fibrosis and increased cardiac GPX activity significantly (p<0.05). However, administration of quercetin and captopril had no effects on plasma NT - proBNP, cardiac and plasma MDA, myocardial fibrosis and GPX activity in uremic rats? heart induced by 5/6 nephrectomy.

Conclusion: Uremic rats? heart induced by 5/6 nephrectomy demonstrated mild myocardial fibrosis but preserved in vivo cardiac function. Increased GPX activity in uremic rats? heart compared to normal control (p<0.05) suggests induction of antioxidant defense mechanisms that might not be exhausted yet highlighting a compensatory phase which was unchanged following chronic either quercetin or captopril administration."

"[ABSTRAKPenghambat pompa proton (PPP) adalah salah satu contoh obat yang digunakan secara luas di dunia. Efikasi dan profil keamanan yang baik dari PPP berperan dalam terjadinya peresepan berlebihan di fasilitas pelayanan kesehatan. Data terkini menunjukan bahwa PPP berhubungan dengan peningkatan risiko pneumonia nosokomial. Penggunaan PPP intravena yang tidak tepat telah berkontribusi dalam meningkatkan total biaya kesehatan serta mengurangi ketersediaan obat. Penelitian retrospektif observasional ini bertujuan untuk menganalisa total konsumsi PPP, total penggunaan sediaan PPP intravena, ketepatan penggunaan sediaan PPP intravena, ketepatan frekuensi penggunaan PPP, dan kejadian pneumonia nosokomial yang berhubungan dengan obat ini. Data diambil dari rekam medik pasien yang masuk ruang rawat inap Ilmu Penyakit Dalam RSCM selama periode Oktober hingga Desember 2014. Pada penelitian ini, dari 210 pasien yang dievaluasi, terdapat 166 pasien (79%) menggunakan PPP, frekuensi ini lebih tinggi dari yang ditemukan pada rumah sakit di US (40-70%) dan di China (42%). Total konsumsi tercatat sebesar 194.31 defined daily dose (DDD)/ 100 bed-days, jauh lebih tinggi dibandingkan yang ditemukan di Irlandia dan India (56.73 dan 128 DDD/ 100 bed-days). Sediaan intravena diberikan pada 87.35% pasien dan hanya 34.48% pasien memiliki indikasi yang tepat. Frekuensi penggunaan diberikan tanpa diturunkan pada beberapa pasien. Persentase pneumonia nosokomial tujuh hingga delapan kali lipat lebih tinggi pada kelompok PPP dibandingkan kelompok non-PPP. Namun, peranan beberapa faktor risiko terhadap terjadinya pneumonia nosokomial tidak dapat disingkirkan.

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ABSTRACTProton pump inhibitors (PPIs) are among the most widely used drugs in the world. The favorable efficacy and safety profile of these drugs has led to their over prescriptions in health care facilities. Recent data, however, has shown that the use of PPIs was associated with the increased risk of nosocomial pneumonia. Inappropriate use of intravenous PPIs has contributed to the increasing of total health cost and also decreasing the source of drugs. This retrospective, observational study was aimed to analyze the total consumption of PPIs, the total use of intravenous PPIs preparations, the appropriateness use of intravenous PPIs preparations, the appropriateness of the frequency of PPIs adminstration, and the occurance of nosocomial pneumonia related to PPIs use. Data were obtained from medical records of patients who came to Internal Medicine Ward RSCM during the period of October to Desember 2014. In this study, out of 210 patients evaluated, 166 patients (79%) used PPIs, the frequency is higher than those in hospitals in the US (40 to 70%) and in China (42%). The total consumption of PPIs was 194.31 defined daily dose (DDD)/ 100 bed-days, which is much higher compared to those in Ireland and India (56.73 and 128 DDD/ 100 bed-days). Intravenous preparations were admistered to 87.35% of patients, among which only 34.48% had been given for appropriate indications. There are no reduced of frequent used in some patients. The frequency of nosocomial pneumonia was seven to eight times higher among patients treated with PPIs compared to those without PPIs. However, the role of some risk factors that may contribute the occurance of nosocomial pneumonia cannot be ruled out.;Proton pump inhibitors (PPIs) are among the most widely used drugs in the world. The favorable efficacy and safety profile of these drugs has led to their over prescriptions in health care facilities. Recent data, however, has shown that the use of PPIs was associated with the increased risk of nosocomial pneumonia. Inappropriate use of intravenous PPIs has contributed to the increasing of total health cost and also decreasing the source of drugs. This retrospective, observational study was aimed to analyze the total consumption of PPIs, the total use of intravenous PPIs preparations, the appropriateness use of intravenous PPIs preparations, the appropriateness of the frequency of PPIs adminstration, and the occurance of nosocomial pneumonia related to PPIs use. Data were obtained from medical records of patients who came to Internal Medicine Ward RSCM during the period of October to Desember 2014. In this study, out of 210 patients evaluated, 166 patients (79%) used PPIs, the frequency is higher than those in hospitals in the US (40 to 70%) and in China (42%). The total consumption of PPIs was 194.31 defined daily dose (DDD)/ 100 bed-days, which is much higher compared to those in Ireland and India (56.73 and 128 DDD/ 100 bed-days). Intravenous preparations were admistered to 87.35% of patients, among which only 34.48% had been given for appropriate indications. There are no reduced of frequent used in some patients. The frequency of nosocomial pneumonia was seven to eight times higher among patients treated with PPIs compared to those without PPIs. However, the role of some risk factors that may contribute the occurance of nosocomial pneumonia cannot be ruled out., Proton pump inhibitors (PPIs) are among the most widely used drugs in the world. The favorable efficacy and safety profile of these drugs has led to their over prescriptions in health care facilities. Recent data, however, has shown that the use of PPIs was associated with the increased risk of nosocomial pneumonia. Inappropriate use of intravenous PPIs has contributed to the increasing of total health cost and also decreasing the source of drugs. This retrospective, observational study was aimed to analyze the total consumption of PPIs, the total use of intravenous PPIs preparations, the appropriateness use of intravenous PPIs preparations, the appropriateness of the frequency of PPIs adminstration, and the occurance of nosocomial pneumonia related to PPIs use. Data were obtained from medical records of patients who came to Internal Medicine Ward RSCM during the period of October to Desember 2014. In this study, out of 210 patients evaluated, 166 patients (79%) used PPIs, the frequency is higher than those in hospitals in the US (40 to 70%) and in China (42%). The total consumption of PPIs was 194.31 defined daily dose (DDD)/ 100 bed-days, which is much higher compared to those in Ireland and India (56.73 and 128 DDD/ 100 bed-days). Intravenous preparations were admistered to 87.35% of patients, among which only 34.48% had been given for appropriate indications. There are no reduced of frequent used in some patients. The frequency of nosocomial pneumonia was seven to eight times higher among patients treated with PPIs compared to those without PPIs. However, the role of some risk factors that may contribute the occurance of nosocomial pneumonia cannot be ruled out.]"

"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.

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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."

"Latar Belakang: Penyakit Ginjal Kronik PGK merupakan masalah kesehatan di seluruh penjuru dunia. PGK menjadi penyebab menurunnya kualitas hidup penderitanya sekaligus meningkatkan risiko kematian. Penyakit Ginjal Kronik ditandai dengan terjadinya kerusakan ginjal dalam waktu lama dan progresif. Gangguan pada PGK berkaitan dengan kejadian stres oksidatif, yaitu keadaan di mana Reactive Oxygen Species ROS terbentuk melebihi pertahanan antioksidan. Kuersetin sebagai bagian keluarga flavonoid diketahui memiliki aktivitas antioksidan. Penelitian sebelumnya mendapatkan bahwa pemberian kuersetin mampu meningkatkan ekspresi protein Nuclear factor related erythroid factor 2 Nrf2 di dalam nukleus pada tikus yang mengalami PGK. Penelitian ini merupakan penelitian lanjutan untuk mengkonfirmasi apakah peningkatan ekspresi protein Nrf2 di dalam nukleus terjadi pada tahap transkripsi. Metode: Jaringan ginjal tikus Sprague-Dawley dari penelitian terdahulu yang tersimpan pada suhu -80oC, diukur ekspresi mRNA Nrf2, Keap1dan HO1menggunakan qRT PCR. Terdapat 4 kelompok penelitian yaitu kelompok kontrol normal, kelompok dengan nefrektomi 5/6 berturut-turut diberi CMC 0,5, kaptopril 10 mg/kgBB, dan kuersetin 100 mg/kgBB. Ekspresi mRNA Nrf2, Keap1 dan HO1dianalisis statistik menggunakan uji ANOVA yang dilanjutkan dengan multiple comparison post hoc dengan LSD, Kruskal-Wallis untuk data yang tidak memenuhi syarat uji ANOVA dimana perbedaan dianggap bermakna secara statistik bila p.

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Background: Chronic Kidney Disease CKD has been a problem all around the world as it causes the decrease of life quality and also raises the risk of death. Chronic kidney disease characterized with long time and progressively kidney failure. The alteration of CKD correlated to oxidative stress, a condition when Reactive oxygen species ROS produced more than antioxidant defense. Quercetin as a part of flavonoid, has been known to have an antioxidant activity. It has been showed in the previous study that quercetin increased intra nuclear Nuclear factor related erythroid factor 2 Nrf2 . This study proposed to confirm whether the increase of nuclear NRF2 is happened in transcription event.

Method: Kidney tissue of Sprague Dawley rat from previous study which had been saved in 80oC had measured the expression of Nrf2, Keap1 and HO1 mRNA by qRT PCR. There were 4 groups as the previous study, normal control group, 5 6 nephrectomy plus consecutively 0,5 CMC, 10 mg kgBW captopril, and 100 mg kgBW quercetin. Expression of Nrf2, Keap1 and HO1 mRNA had been analyzed statistically with ANOVA test and LSD multiple comparison post hoc. For data that are not fit to analyzed with ANOVA would be analyzed with Kruskal Wallis and Mann Whitney. The data considered as significantly different by p."

"Ekstrak air Hibiscus sabdariffa (HS) telah digunakan sebagai pengobatan tradisional pada terapi hipertensi. Banyak orang menggabungkan penggunaan ekstrak air HS dengan kaptopril sehingga dapat berpotensi menimbulkan interaksi. Penelitian ini bertujuan untuk mengetahui pengaruh koadministrasi ekstrak air HS terhadap profil farmakokinetika kaptopril, tekanan darah, dan biomarkersistem renin angiotensin aldosteron (RAAS). Studi farmakokinetika dilakukan terhadap empat kelompok tikus (n = 6). Kelompok I menerima suspensi kaptopril tunggal (CAP; 4,5 mg/200 g BB) sementara kelompok II, III, dan IV menerima koadministrasi ekstrak air HS (15 mg/200 g BB, 30 mg/200 g BB, dan 60 mg/200g BB) dan kaptopril 4,5 mg/200 g BB. Untuk pengukuran tekanan darah dan level biomarker RAAS, digunakan tujuh kelompok tikus (n = 6) berbeda yang terdiri dari satu kelompok sham dan enam kelompok tikus model 2K1C. Pada tikus model 2K1C, hipertensi diinduksi dengan pemasangan mikroklip stainless steel (ID: 0,20 mm) pada arteri ginjal kiri. Kelompok tikus model terdiri dari kontrol negatif (2K1C, tidak diobati), kontrol positif (4,5 mg/200 g BB kaptopril), ekstrak air HS tunggal (30 mg/200 g BB), dan 3 kelompok koadministrasi yang menerima ekstrak air HS (15, 30, atau 60 mg/200g BB) dan kaptopril 4,5 mg/200 g BB. Pemberian ekstrak dan kaptopril dilakukan secara peroral. Seluruh perlakuan dilakukan selama 2 minggu. Ketiga dosis koadministrasi ekstrak HS dapat mempengaruhi profil farmakokinetika kaptopril secara signifikan. Nilai AUC0-t, AUC0-, dan Cmax, pada kelompok tersebut mengalami penurunan, sementara nilai Cl/F dan Vd/F mengalami peningkatan. Seluruh pemberian terapi pengobatan menyebabkan penurunan tekanan darah secara signifikan mendekati kelompok sham. Level renin plasma, aktivitas serum angiotensin converting enzyme (ACE), dan level angiotensin II plasma pada kelompok 2K1C mengalami kenaikan yang signifikan dibandingkan dengan kelompok sham. Aktivitas serum ACE dan level angiotensin II plasma pada seluruh kelompok terapi mengalami penurunan signifikan dan nilainya mendekati kelompok sham. Ekstrak air HS tunggal dapat menurunkan tekanan darah, namun koadministrasi dengan kaptopril tidak memberikan efek tambahan. Oleh karena itu, dapat disimpulkan bahwa pemberian koadministrasi ekstrak air HS dengan kaptopril dapat mempengaruhi profil farmakokinetika kaptopril secara signifikan, namun tidak memberikan pengaruh yang signifikan terhadap penurunan tekanan darah dan level biomarker RAAS.

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Hibiscus sabdariffa (HS) extract has been used as traditional medicine during management of hypertension. Many people co-administered HS aqueous extract with captopril thus predispose herb-drug interaction. The purpose of this study was to determine the effect of HS aqueous extract co-administration on the pharmacokinetic profile of captopril, blood pressure, and biomarker level of renin angiotensin aldosterone system (RAAS). Pharmacokinetic study was performed on four groups of rats (n = g). Group I received captopril suspension only (CAP; 4.5 mg/200 g BW), while group II, III, and IV received co-administration of Hibiscus sabdariffa extract (15 mg/200 g BW, 30 mg/200 g BW, and 60 mg/200 g BW respectively) and captopril 4.5 mg/200 g BW. Blood pressure and biomarker level of RAAS measurement were performed on another 7 groups (n = 6), a SHAM group and six 2K1C groups. In 2K1C animals, hypertension was induced by placing a stainless micro clip (inner diameter of 0.20 mm) on left renal artery. The 2K1C animals consist of negative control (2K1C, no treatment), positive control (captopril 4.5 mg/200 g BW), HS aqueous extract (30 mg/200 g BW), and three co-administration groups receiving HS aqueous extract (15, 30, or 60 mg/200 g BW) plus 4.5 mg/200 g BW captopril. Extract and captopril administration were given by oral gavage. All treatments were performed for two weeks. Pharmacokinetic profile of captopril was changed significantly by all co-administration doses of HS aqueous extract. The AUC0-t, AUC0-, and Cmax value of those groups were decreased, conversely the Cl/F and Vd/F value were increased. Blood pressure was significantly reduced by all the drug treatments approaching the level of SHAM controls. Plasma renin level, serum angiotensin converting enzyme (ACE) activity, and plasma angiotensin II level were also significantly elevated in the 2K1C group compared to the SHAM group. Both serum ACE activity and plasma angiotensin II level were significantly reduced approaching the SHAM group levels by all the drug treatments. HS aqueous extract can reduce blood pressure but may not provide any additional benefit. Therefore, we can conclude that co-administration of HS aqueous extract with captopril could affect the pharmacokinetic profile significantly, however it didnt have significant effect on the decrease in blood pressure and RAAS biomarker level."

"Berbagai penelitian telah membuktikan khasiat ekstrak air rosella (Hibiscus sabdariffa L) dalam pemeliharaan fungsi kardiovaskular. Penggunaan ekstrak air rosella yang dikoadministrasikan dengan aspirin berpotensi untuk terjadi, karena aspirin merupakan terapi yang juga digunakan dalam pemeliharaan fungsi kardiovaskular, khususnya sebagai antiplatelet. Penelitian ini bertujuan untuk mengetahui pengaruh ekstrak air rosella terhadap farmakokinetik dan farmakodinamik aspirin. Studi interaksi farmakokinetik dan farmakodinamik ekstrak air rosella dengan aspirin terbagi dalam beberapa kelompok perlakuan, yaitu kelompok aspirin tunggal, rosella tunggal dan tiga kelompok ko-administrasi ekstrak air rosella dengan aspirin. Ekstrak air rosella dalam tiga variasi dosis yang diberikan secara ko-administrasi dengan aspirin tidak memberikan pengaruh yang signifikan secara statistik terhadap AUC, Cmaks, tmaks, Vd, Klirens, dan t1/2 asam salisilat. Selain itu, pemberian ekstrak air rosella secara ko-administrasi dengan aspirin tidak memberikan pengaruh yang signifikan terhadap peningkatan waktu perdarahan dan survival rate dari tikus uji. Berdasarkan  hasil penelitian ini disimpulkan, ekstrak air rosella yang digunakan secara ko-administrasi dengan aspirin pada tikus tidak memberikan pengaruh yang signifikan terhadap farmakokinetik dan farmakodinamik aspirin.

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Various studies have proven the efficacy of Roselle (Hibiscus sabdariffa L) in maintaining cardiovascular function. The use of aqueous extract of Roselle with aspirin has the potential to occur, because aspirin is a therapy that is also used in the maintenance of cardiovascular function, especially as antiplatelet. This study aimed to determine the effect of aqueous extract of Roselle on the pharmacokinetics and pharmacodynamics of aspirin. The study of pharmacokinetic and pharmacodynamic interactions of aqueous extract of Roselle with aspirin was divided into several treatment groups: single aspirin group, single Roselle and three co-administration groups of aqueous extract of Roselle with aspirin. Co-administration aqueous extract of Roselle with aspirin did not have a significant difference on AUC, Cmax, Tmax, Vd, clearance, and t½ salicylic acid. In addition, co-administration aqueous extract of Roselle and aspirin did not show a significant increase in the bleeding time and survival rate of rats. In conclusion, aqueous extract of Roselle used by co-administration with aspirin in rats did not have a significant effect on the pharmacokinetics and pharmacodynamics of aspirin."