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"ABSTRAKLatar Belakang: Alfacalcidol, sebuah vitamin D analog, potensial bermanfaat memperbaiki imunosenesens pada pasien usia lanjut dengan sindrom frailty karena bekerja sebagai anti inflamasi melalui Vitamin D Receptor VDR pada makrofag dan sel TTujuan: Mengkaji efek pemberian alfacalcidol in vitro dan in vivo terhadap perubahan sitokin inflamasi IL-6, IL-10 dan Interferon g serta subset limfosit T rasio CD4/CD8, persentase sel T CD 8 CD28- dari kultur Peripheral Blood Mononuclear Cell PBMC dan Immune Risk Profile IRP pada usila dengan sindrom frailtyMetode: Selama Januari sampai Juli 2017 di RS Cipto Mangunkusumo Jakarta, direkrut masing-masing 8 orang subyek usila fit, pre-frail dan frail dan 10 subyek dewasa sehat sebagai kontrol. Pada 34 subyek ini dinilai perubahan kadar IL-6, IL-10 dan IFN g yang diukur dengan kit ELISA dari supernatan kultur PBMC 24 jam yang distimulus Lipopolisakarida LPS 100 ng/ml dengan dan tanpa pretreatment alfacalcidol in vitro. Selain itu juga dilakukan uji klinis acak tersamar ganda dengan pemberian alfacalcidol 0,5 mcg 90 hari pada 110 subyek berusia lanjut lalu diamati perubahan kadar IL-6, IL-10 dan IFN , g perubahan rasio CD4/CD8 dan persentase sel T CD8 CD28- serta penilaian Immune Risk Profile. Dilakukan uji t tidak berpasangan untuk mengetahui perbedaan rerata kadar sitokin dan persentase populasi sel T dan uji chi square untuk menilai beda proporsi subyek dengan IRP positif.Hasil: Pada penelitian in vitro didapatkan rerata kadar 25 OH D serum yang semakin menurun seiring dengan perburukan status frailty. Alfacalcidol in vitro tidak menurunkan IL-6 dan IFN g, namun meningkatkan IL-10 pada seluruh kelompok. Dari uji klinis didaparkan alfacalcidol 0,5 mcg selama 90 hari tidak menurunkan IL-6 p=0,4 dan IFN gamma p=0,001 , namun mampu meningkatkan IL-10 p=0,005 dan menurunkan rasio IL6/IL10 p=0,008 . Alfacalcidol meningkatkan rasio CD4/CD8 dari 2,68 SB 2,45 menjadi 3,2 SB 2,9 ; p=0,001 dan menurunkan persentase CD8 CD28- dari 5,1 SB 3,96 menjadi 2,5 1,5 ; p

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ABSTRACTIntroduction Chronic low grade inflammation and dysregulation of cellular immunity are the cardinal signs of immunosenescence in elderly with frailty syndrome. Alphacalcidol, a vitamin D analog shows immunoregulatory potency as it works on the macrophage and T cell, to control inflammation and T cell dysregulation in the elderly.Objective to determine the effect of alphacalcidol on inflammatory cytokines IL 6, IL 10, IFN gamma and T cell subsets CD4 CD8 ratio and CD8 CD28 and Immune Risk Profile of the elderly with frailty syndromeMethods During January to August 2017, in vitro study was conducted involving 10 healthy adults volunteer and 8 elderly each in fit, pre frail and frail category from Outpatient Clinics of Cipto Mangunkusumo Hospital Jakarta Indonesia using 24h Peripheral Blood Mononuclear Cells PBMC culture supernatants to determine the change of IL 6, IL 10 and g IFN level measured by ELISA, following stimulation with Lipopolisaccharide LPS 100 nm, with and without pretreatment with alphacalcidol. A double blind randomized controlled trial RCT with allocation concealment, involving 110 elderly subjects was also conducted to measure the effect of 0,5 mcg alphacalcidol administration for 90 days on inflammatory cytokines IL 6, IL 10, g IFN from 24 h PBMC culture supernatant, as well as CD4 CD8 and CD8 CD28 count and change of Immune Risk Profile. Statistical analysis was performed using t test to measure mean difference of cytokines and T cell count and chi square to measure proportion difference of IRP.Result In vitro study using PBMC showed alphacalcidol administration did not decrease IL 6 level IL p 0,24 and g IFN p 0,36 , but it increased IL 10 p 0,02 . Of 110 subjects involved in the RCT consisting of 27 fit elderly, 27 pre frail elderly and 56 frail elderly, it can be observed that Alphacalcidol 0,5 mcg for 90 did not decrease IL 6 p 0,4 and g IFN p 0,001 , but increased IL 10 p 0,005 and decrease IL6 IL10 ratio p 0,008 . Alphacalcidol increased CD4 CD8 ratio from 2,68 SD 2,45 to 3,2 SD 2,9 p 0,001 and decrease CD8 CD28 percentage from 5,1 SD 3,96 to 2,5 1,5 p"

"ABSTRACTBACKGROUND: Alphacalcidol, a vitamin D analog, shows immune regulatory potency as it works on the macrophage and T cell to control inflammation and T cell dysregulation in elderly. None has been known about its effect on elderly with various states of frailty syndrome, which have different level of chronic low grade inflammation. This study aimed to determine the effect of alphacalcidol on inflammatory cytokines (IL-6, IL-10, g-IFN ) and T cell subsets (CD4/CD8 ratio and CD8+ CD28-) of elderly with various stages of frailty syndrome. METHODS: from January to July 2017, a double blind randomized controlled trial (RCT) with allocation concealment, involving 110 elderly subjects from Geriatric Outpatient Clinic Cipto Mangunkusumo Hospital Jakarta, was conducted to measure the effect of 0.5 mcg alphacalcidol administration for 90 days to inflammatory cytokines (IL-6, IL-10, g-IFN) from PBMC culture supernatant, as well as CD4/CD8 and CD8+CD28- percentage using flow cytometry. Statistical analysis using SPSS version 20 was performed with t-test to measure mean difference. RESULTS: of 110 subjects involved in the RCT consisting of 27 fit, 27 pre-frail and 56 frail elderly, 25(OH)D serum level was found to be as low as 25.59 (12.2) ng/ml in alphacalcidol group and 28.27 (10.4) ng/ml in placebo group. Alphacalcidol did not decrease IL-6 (p=0.4) and g- IFN (p=0.001), but it increased IL-10 (p=0,005) and decreased IL6/IL10 ratio (p=0.008). Alphacalcidol increased CD4/CD8 ratio from 2.68 (SD 2.45) to 3.2 (SD 2.9); p=0.001 and decreased CD8+ CD28- percentage from 5.1 (SD 3.96) to 2.5 (1.5); p<0.001. Sub group analysis showed similar patterns in all frailty states. CONCLUSION: Alphacalcidol improves immune senescence by acting as anti-inflammatory agent through increased IL-10 and decreased IL6/IL-10 ratio and also improves cellular immunity through increased CD4/CD8 ratio and decreased CD8+ CD28- subset in elderly. This effect is not influenced by frailty state."

"Penelitian ini ingin membuktikan terjadinya kesinergisan pembentukan DNA Adduct secara in-vivo pada urin dan plasma tikus yang diberi paparan Nonil fenol (NP) dan Tembaga (Cu) ditandai dengan terbentuknya 8-hydroxy-2-deoxyguanosine (8-OHdG) sebagai produk awal terjadinya kerusakan DNA dan juga secara in-vitro melalui reaksi Fenton dengan mereaksikan 2deoxyguanosine (dG) dengan NP dan Cu dengan bantuan H2O2 pada suhu 37˚C dan variasi waktu inkubasi 7 jam dan 24 jam. Treatment hewan dilakukan selama 21 hari untuk mendapatkan kumpulan plasma dan urin. Plasma tikus dianalisis menggunakan kit ELISA sedangkan urin tikus dan hasil invitro dianalisa menggunakan HPLC untuk mengetahui konsentrasi 8-OHdG yang terbentuk. Dari hasil penelitian, baik in vivo dan in vitro sama sama ditemukan pembentukan 8-OHdG. Pada sampel urin terdapat kesinergisan 8-OHdG yang terbentuk sejak pertama kali paparan sampai akhir paparan ditandai dengan meningkatknya konsentrasi 8-OHdG pada kombinasi paparan NP dan Cu sebesar 331,93 ppb dibanding dengan paparan NP saja sebesar 282,70 ppb. Hasil yang sama di temukan pada uji in vitro dengan variasi waktu inkubasi kelompok reaksi tanpa menggunakan Cu konsentrasi 8-OHdG nya lebih rendah dari kelompok paparan yang menggunakan Cu yakni masing-masing sebesar 867,52 ppb dan 926,97 ppb. Pada plasma tidak ditemukan efek sinergis antara NP dan Cu pada pembentukan 8-OHdG dikarenakan pada saat pemisahan plasma dari darah, terjadi lisis darah sehingga kurang optimal dalam analisa.

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This study wanted to prove the synergy of the formation of DNA adduct in-vivo in the urine and plasma of rats given exposure to Nonyl phenol (NP) and Copper (Cu) marked by the formation of 8-hydroxy-2-deoxyguanosine (8-OHdG) as the initial product DNA damage and also in vitro through the Fenton reaction by reacting 2 deoxyguanosine with NP and Cu with the help of H2O2 at 37C and varying incubation times 7 hours and 24 hours. Animal treatment is carried out for 21 days to get a collection of plasma and urine. Plasma, urine, and in vitro results were then analyzed using ELISA kits and HPLC to determine the concentration of 8-OHdG formed. From the results of the study, both in vivo and in vitro were found to form 8-OHdG. In the urine sample there is a synergy of 8-OHdG that is formed from the first exposure to the end of the exposure marked by an increase in the concentration of 8-OHdG in a combination of NP and Cu exposure of 331,93 ppb compared to NP exposure alone of 282,70 ppb. The same results were found in the in vitro test with the incubation time variation of the reaction group without using Cu the concentration of 8-OHdG was lower than the exposure group using Cu which were 867,52 ppb and 926,97 ppb, respectively. In the plasma there is no synergistic effect between NP and Cu in the formation of 8-OHdG because during the separation of plasma from the blood, blood lysis occurs so that it is less than optimal in the analysis."

"Plastik merupakan bahan yang banyak digunakan dalam peralatan keseharaian. Penambahan zat tertentu pada alat berbahan plastik ini diketahui dapat menambah kualitas, yaitu lebih elastis, kuat dan tahan lama. Salah satu bahan aditif yang biasa digunakan yaitu ftalat. Senyawa ftalat dapat berpotensi menghasilkan terjadinya DNA adduct. Penelitian ini mempelajari mengenai pembentukan 8-OHdG akibat paparan senyawa ftalat dan logam Cu (II) secara in vitro dan in vivo pada tikus (Rattus novergicus). Pembentukan 8-OHdG dianalisa secara in vitro dengan menggunakan HPLC, dengan variasi pH, waktu inkubasi dan perbandingan konsentrasi. Sedangkan secara in vivo pada tikus, sampel darah dianalisa menggunakan ELISA Kit dan sampel urin menggunakan instrumen LC-MS/MS. Secara umum, konsentrasi 8-OHdG paling besar pada sampel 2-dG diinkubasi dengan kombinasi larutan H₂O₂, ftalat, dan Cu (II). Pada studi in vitro dengan variasi pH menunjukkan konsentrasi 8-OHdG yang lebih tinggi pada pH 7,4; pada variasi waktu inkubasi lebih besar kosentrasi 8-OHdG pada 32 jam; dan pada variasi konsentrasi lebih besar pada perbandingan 1:20. Hasil studi in vivo menggunakan ELISA Kit, konsentrasi 8-OHdG yang terbentuk menunjukkan nilai paling besar pada sampel darah kelompok tikus terpapar ftalat kombinasi Cu (II) yaitu 5,26 ppb; kelompok tikus terpapar ftalat sebesar 4,29 ppb; dan kelompok tikus kontrol (tanpa paparan) sebesar 2,58 ppb. Sedangkan uji in vivo menggunakan LC-MS/MS pada sampel urin tikus juga menunjukkan konsentrasi 8-OHdG paling besar pada tikus kelompok ftalat kombinasi Cu (II) sebesar 174,1 ppb; dan tikus kelompok ftalat sebesar 156,5 ppb.

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Plastic is a material that is widely used in everyday appliances. The addition of certain substances to plastic tools is known to add quality, namely more elastic, strong and durable. One of the additives commonly used is phthalate. Phthalate compounds can potentially produce DNA adducts. This research studies the formation of 8-OHdG due to exposure to phthalate compounds and Cu (II) metal in vitro and in vivo in rats (Rattus novergicus). The formation of 8-OHdG was analyzed in vitro using HPLC, with variations in pH, incubation time and concentration ratio. While in vivo in rats, blood samples were analyzed using ELISA Kit and urine samples using LC-MS/MS instrument. In general, the concentration of 8-OHdG was greatest in 2-dG samples incubated with a combination of H2O2, phthalate, and Cu (II) solutions. In vitro studies with variations in pH showed higher concentrations of 8-OHdG at pH 7.4; at variations in incubation time the concentration of 8-OHdG was greater at 32 hours; and at variations in concentration greater at a ratio of 1:20. The results of the In vivo study using ELISA Kit, the concentration of 8-OHdG formed showed the greatest value in the blood samples of the rat group exposed to phthalate combined with Cu (II), which was 5.26 ppb; the rat group exposed to phthalate was 4.29 ppb; and the control rat group (without exposure) was 2.58 ppb. While the In vivo test using LC-MS/MS on rat urine samples also showed the highest concentration of 8-OHdG in rats of the Cu (II) phthalate combination group at 174.1 ppb; and rats of the phthalate group at 156.5 ppb."

"Latar Belakang: Pendekatan indeks frailty 40 item (FI-40) dianggap sebagai alat terbaik untuk evaluasi mortalitas dan hospitalisasi sindrom frailty, tetapi sulit diterapkan dalam praktik klinis sehari-hari. Pendekatan dengan sistem skor CHS, SOF, dan FI-CGA lebih mudah diterapkan dalam praktik klinis sehari-hari, namun hingga saat ini belum ada data validasi di Indonesia. Tujuan: Mendapatkan rekomendasi mengenai alat ukur sindrom frailty yang mudah diterapkan dalam praktik klinis sehari-hari di Indonesia. Metode: Penelitian ini merupakan studi potong lintang dengan pendekatan uji diagnostik yang dilakukan pada pasien di poliklinik Geriatri Rumah Sakit Cipto Mangunkusumo, dengan usia ≥60 tahun, pada periode Mei-Juni 2013. Setiap subjek dinilai menggunakan sistem skor CHS, SOF, FI-CGA, dan FI-40. Dilakukan penilaian sensitivitas, spesifisitas, nilai prediksi positif (NPP), nilai prediksi negatif (NPN), rasio kemungkinan positif (RK+), dan rasio kemungkinan negatif (RK-) untuk masing-masing sistem skor CHS, SOF, dan FI-CGA dibandingkan dengan FI-40. Hasil: Proporsi individu yang termasuk dalam kategori frail, pre-frail, dan fit berdasarkan indeks frailty 40 item berturut-turut adalah 25,3%, 71%, dan 3,7%. Untuk membedakan individu frail dengan tidak frail, skor CHS memiliki sensitivitas 41,2%, spesifisitas 95%, NPP 73,7%, NPN 82,7%, RK+ 8,41 dan RK- 0,62. Skor SOF memiliki sensitivitas 17,6%, spesifisitas 99,5%, NPP 92,3%, NPN 78,1%, RK+ 35,2 dan RK- 0,83. Sedangkan skor FI-CGA memiliki sensitivitas 8,8%, spesifisitas 100%, NPP 100%, NPN 76,4%, RK+ tak terbatas, dan RK- 0,91. Kesimpulan: Tidak ada sistem skor yang dapat digunakan sebagai alat skrining yang baik untuk sindrom frailty, namun masing-masing sistem skor dapat digunakan sebagai alat diagnostik yang baik untuk sindrom frailty.

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Background: The Frailty Index 40-item (FI-40) approach is considered the best tool for evaluating mortality and hospitalization outcomes related to frailty syndrome, although it is challenging to implement in daily clinical practice. The CHS, SOF, and FI-CGA scoring systems are easier to use in daily practice, but there is no validation data available in Indonesia.

Aim: To obtain recommendations for a frailty syndrome diagnostic tool that is easy to implement in daily clinical practice in Indonesia.

Methods: This was a cross-sectional study with a diagnostic test approach conducted on patients aged ≥60 years at the Geriatric Outpatient Clinic of Cipto Mangunkusumo Hospital from May to June 2013. Each subject was assessed using the CHS, SOF, FI-CGA, and FI-40 scoring systems. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated for each scoring system compared to FI-40.

Results: The proportions of frail, pre-frail, and robust individuals based on the 40-item frailty index were 25.3%, 71%, and 3.7%, respectively. To differentiate between frail and non-frail individuals, the CHS score showed a sensitivity of 41.2%, specificity of 95%, PPV of 73.7%, NPV of 82.7%, LR+ of 8.41, and LR- of 0.62. The SOF score showed a sensitivity of 17.6%, specificity of 99.5%, PPV of 92.3%, NPV of 78.1%, LR+ of 35.2, and LR- of 0.83. The FI-CGA score showed a sensitivity of 8.8%, specificity of 100%, PPV of 100%, NPV of 76.4%, LR+ infinite, and LR- of 0.91.

Conclusion: No scoring system was found to be suitable as a screening tool for frailty syndrome; however, all scoring systems can be used as effective diagnostic tools for frailty with good predictive ability."

"ABSTRAKAktivitas oksidan dan radikal bebas di dalam tubuh yang tidak diimbangi oleh antioksidan dapat menimbulkan penyakit kronik dan degeneratif. Oksidan dan radikal bebas adalah molekul yang reaktif dan tidak stabil karena adanya elektron tidak berpasangan, sedangkan antioksidan adalah senyawa pemberi elektron yang dapat menetralisir oksidan dan radikal bebas. Antioksidan dapat diklasifikasikan menjadi endogen dan eksogen, serta antioksidan eksogen buatan dan alami. Salah satu sumber antioksidan alami yang belum diteliti adalah daun alpukat. Untuk mengetahui ada atau tidaknya aktivitas antioksidan di dalam ekstrak daun alpukat, dilakukan uji secara In Vitro dengan DPPH 2,2-difenil-1-pikril hidrazil sebagai radikal buatan yang larut di dalam pelarut polar dan pengukuran nilai IC50. Untuk mengetahui dosis efektif dari aktivitas antioksidan ekstrak daun alpukat, dilakukan uji secara In Vivo dengan lima kelompok uji tikus putih galur Wistar dan pengukuran kadar MDA Malondialdehid plasma sebagai hasil peroksidasi lipid pada sebelum dan setelah perlakuan. Perlakuan yang diberikan adalah pemberian vitamin C pada kelompok tikus kontrol positif, air pada kelompok tikus kontrol negatif, ekstrak daun alpukat sebanyak 4 mg/200 gram BB, 8 mg/200 gram BB, dan 16 mg/200 gram BB pada kelompok uji tikus pertama, kedua, dan ketiga, serta aktivitas fisik berupa berenang selama 15 menit untuk meningkatkan peroksidasi lipid yang terjadi di dalam tubuh tikus. Berdasarkan hasil penelitian, ekstrak daun alpukat yang dilarutkan di dalam air dan etanol memiliki nilai IC50 yang dikategorikan sebagai aktivitas antioksidan sangat kuat, dan dosis yang dapat menurunkan kadar MDA paling baik adalah sekitar 8 mg per 200 gram BB, walaupun nilai penurunan tersebut tidak bermakna secara statistik.

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ABSTRAKThe inequality of the activity of oxidants and free radicals in body with the activity of antioxidants can result in degenerative and chronic diseases. Oxidants and free radicals are reactive molecules with one or more unpaired electrons, meanwhile antioxidants are molecules that can give electrons to make the oxidants and free radicals stable. Antioxidants can be classified into endogenous and exogenous, and also the synthetic and natural of exogenous antioxidants. One of the sources of natural exogenous antioxidants is the avocado leaves. In Vitro test with DPPH as the polar soluble synthetic radical and the measurement of IC50 was done to know the activity of antioxidants in avocado leaves extract. Effective dose of antioxidant activity in avocado leaves extract was known through the In Vivo test using five groups of Wistar albino rats and the measurement of MDA plasm as the result of lipid peroxidation in before and after experiments. The first group of Wistar albino rats was given vitamin C as positive control, the second one was given water as negative control, the third one was given 4 mg per 200 gram weight of Avocado leaves extract, the fourth one was given 8 mg per 200 gram weight of Avocado leaves extract, and the fifth one was given 16 mg per 200 gram weight of Avocado leaves extract, and in the last day of experiments, all of rats had to swim in 15 minutes to increase the lipid peroxidation in their bodies. The result shows that Avocado leaves extracts in water and ethanol have the highest IC50. The best dose of Avocado leaves extract in reducing the MDA plasm is approximately 8 mg per 200 gram weight, though the reduced value is not statistically significant. "

"Diabetes melitus (DM) tipe 2 adalah penyakit yang berhubungan dengan kondisi inflamasi ringan kronis. Selain terjadi peningkatan kadar sitokin proinflamasi, diduga terjadi gangguan pada mediator antiinflamasi, yaitu enzim indoleamine 2,3-dioxygenase (IDO). Tujuan dari penelitian ini adalah menganalisis produksi IDO dari kultur peripheral blood mononuclear cells (PBMC) pada penderita DM tipe 2 dan meneliti hubungan IDO dengan kadar sitokin proinflamasi seperti TNF-α, IL-6, dan IFN-γ; serta sitokin antiinflamasi, IL-10. Sampel PBMC diambil dari 21 pasien DM tipe 2 dan 17 subjek kontrol sehat kemudian dilakukan kultur dengan stimulasi phytohemagglutinin (PHA). Setelah kultur selama 3 hari, produksi TNF-α, IL-6, IFN-γ, dan IL-10 diukur menggunakan multiplex immunoassay, sedangkan kadar IDO diukur menggunakan ELISA. Kadar IDO dari kultur PBMC tanpa stimulasi dan dengan stimulasi PHA secara signifikan lebih tinggi pada pasien DM tipe 2 dengan p<0,001 dan p=0,012. Sebanyak 52,8% pasien DM tipe 2 mengalami penurunan produksi IDO setelah distimulasi PHA dan hal tersebut berhubungan dengan kadar IFN-γ yang rendah dengan p=0,005. Di lain pihak, 42,8% pasien DM tipe 2 mengalami peningkatan produksi IDO setelah stimulasi PHA dan hal ini berhubungan dengan rasio TNF-α/IL-10 (r=0,513 p=0,079), IL-6/IL-10 (r=0,446 p=0,114) dan IFN-γ/IL-10 (r=0,422 p=0,129). Pada DM tipe 2, terjadi perubahan produksi IDO. IFN-γ yang rendah berkontribusi pada penurunan produksi IDO. Sementara itu, respon proinflamasi berhubungan dengan peningkatan produksi IDO.

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Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammatory condition. Besides the increased of proinflammatory cytokines level, it was found that anti-inflammatory mediators were disturbed. So, we would analyse the production of indoleamine 2,3-dioxygenase (IDO) in PHA-stimulated PBMC from type 2 DM patients and investigate its association to pro and anti-inflammatory cytokines. PBMC samples were collected from 21 patients with T2DM and 17 healthy subjects, then followed by 3-day PHA stimulation. In vitro production of TNF-α, IL-6, IFN-γ and IL-10 were measured using multiplex immunoassay; meanwhile, IDO level was assessed using ELISA. IDO concentration from unstimulated and PHA-stimulated PBMC were significantly higher in T2DM patients with p<0,001 and p=0.012 respectively. Reduced IDO production occurred in 52,8% of T2DM and it was associated with low interferon γ with p=0.005; whereas 42,8% of T2DM had higher IDO production and had moderate positive correlations with ratio of TNF-α/IL-10 (r=0,513 p=0,079), IL-6/IL-10 (r=0,446 p=0,114) and IFN-γ/IL-10 (r=0,422 p=0,129). We could conclude that there is an alteration of IDO production after PHA stimulation in T2DM. Low interferon γ level seems to contribute in reducing IDO production. In T2DM with higher IDO production, proinflammatory responses are more influential in increasing IDO production."