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Abstrak :
ABSTRAK
Diabetes melitus tipe 2 (DMT2) adalah jenis diabetes yang paling umum di dunia. Baris kedua pengobatan DMT2 yang dapat menghambat pelepasan glukagon dan meningkatkan sekresi insulin adalah inhibitor DPP-IV. Enzim DPP-IV yang terdapat dalam tubuh manusia dapat diproduksi oleh tubuh sendiri atau dari bakteri yang terdapat di usus, seperti Parabacteroides goldsteinii dan Bacteroides fragilis. Dalam penelitian ini dilakukan penyelarasan sekuens bakteri dan pemodelan homologi. Docking makromolekul DPP-IV manusia dan model bakteri dilakukan terhadap setiap situs aktif DPP-IV manusia menggunakan aplikasi PyRx. Persentase kemiripan urutan antara DPP-IV manusia dan model DPP-IV bakteri (% urutan yang dipertahankan;% dari semua urutan), P.goldsteinii (46,15%, 24,18%) dan B. fragilis (92,31%; 20, 04% ). Parameter optimasi untuk molecular docking DPP-IV yaitu kotak grid dengan ukuran 50x50x50 unit dengan jarak spasi 0,375 dan evaluasi energi sebesar 5.000.000. Berdasarkan hasil analisis nilai indeks selektivitas diperoleh senyawa penghambat DPP-IV yaitu gemigliptin yang relatif selektif pada P.goldsteinii dengan nilai indeks selektivitas 1,34 x10-4 dan retagliptin yang relatif selektif pada B. fragilis dengan nilai indeks selektivitas 0,05 x10 -4 diantara 16 ligan lain pada tiga sisi aktif enzim DPP-IV. Hasil ini menunjukkan bahwa gemigliptin dan retagliptin dapat digunakan sebagai data pendukung dalam perancangan molekul baru dan perkembangannya sebagai penghambat DPP-IV selektif untuk pasien diabetes melitus tipe 2 (DMT2).
ABSTRACT
Diabetes mellitus type 2 (T2DM) is the most common type of diabetes in the world. The second line of T2DM treatment that can inhibit glucagon release and increase insulin secretion are DPP-IV inhibitors. The DPP-IV enzyme found in the human body can be produced by the body itself or from bacteria found in the intestines, such as Parabacteroides goldsteinii and Bacteroides fragilis. In this study, bacterial sequence alignment and homology modeling were carried out. Docking of human DPP-IV macromolecules and bacterial models was carried out against each active human DPP-IV site using the PyRx application. Percentage of sequence similarity between the human DPP-IV and the bacterial DPP-IV model (% retained sequences;% of all sequences), P.goldsteinii (46.15%, 24.18%) and B. fragilis (92.31%; 20, 04%). The optimization parameters for the DPP-IV molecular docking are a grid box with a size of 50x50x50 units with a spacing of 0.375 and an energy evaluation of 5,000,000. Based on the results of the selectivity index value analysis, the DPP-IV inhibitor compound was obtained, namely gemigliptin which was relatively selective in P.goldsteinii with a selectivity index value of 1.34 x10-4 and retagliptin which was relatively selective in B. fragilis with a selectivity index value of 0.05 x10-4. among 16 other ligands on the three active sites of the DPP-IV enzyme. These results indicate that gemigliptin and retagliptin can be used as supporting data in the design of new molecules and their development as selective DPP-IV inhibitors for type 2 diabetes mellitus (T2DM) patients.

Abstrak :
Penyakit gigi dengan prevalensi tinggi di Indonesia dan di beberapa negara lain ialah periodontitis dan karies, yang sampai kini masih merupakan masalah kesehatan. bakteri penyebab penyakit gigi antara lain Streptococcus mutans dan Bacteroides melaninogenicus. Kedua jenis bakteri ini dapat menjalar ke organ lain dan menyebabkan penyakit yang berakibat fatal. Salvadora persica (pohon arak, siwak) sudah lama dipakai sebagai alat pembersih gigi di Timur Tengah, Afrika dan beberapa negara Asia lainnya. Pada penelitian ini dilakukan uji antibakteri ekstrak dan kristal siwak terhadap Streptococcus mutans dan Bacteroides melaninogenicus. Metode yang digunakan dalam penelitian ini ialah metode dilusi, yaitu makro dan mikro dilusi, untuk menentukan Konsentrasi Hambat Minimal (KHM). Hasil KHMI dari ekstrak siwak terhadap Streptococcus mutans sebesar 6.25%, sedangkan terhadap Bacteroides melaninogenicus 1.56%. Untuk KHM kristal siwak terhadap Streptococcus mutans ditemukan 12.5% dan terhadap Bacteroides melaninogenicus 3.12%. Dari penelitian ini dapat disimpulkan bahwa daya antibakteri ekstrak dan kristal Salvadora persica lebih baik terhadap B. melaninogenicus dari pada daya hambat pertumbuhan terhadap S. mutans, kemungkinan B. melaninogenicus lebih peka terhadap siwak atau S. mutans lebih virulen daripada B. melaninogenicus

Antibacterial Activity of Siwak (Salvadora persica Linn.) against Streptococcus mutans (ATC31987) and Bacteroides melaninogenicus. Dental diseases with high prevalences in Indonesia and also in some other countries are periodontitis and caries. Both diseases are until now still a health problem. Bacteria causing dental diseases are for examples Streptococcus mutans and Bacteroides melaninogenicus, which both can spread to other organs and cause fatal diseases. Salvadora persica (arak, siwak) has been used for a long time ago as a tool for teeth cleanser in the Middle East, Africa and several Asian countries. In this study, we have done antibacterial tests of the extract and crystal of siwak against Streptococcus mutans and Bacteroides melaninogenicus. In determining the Minimal Inhibitory Concentration (MIC), the macro and micro dilution methods were used. The result showed that MIC of siwaks’ extract against Streptococcus mutans was 6.25%, and against Bacteroides melaninogenicus 1.56%. Minimal Inhibitory Concentration of siwaks’ crystal against Streptococcus mutans and Bacteroides melaninogenicus was 12.5%, and 3.12% respectively. This study showed that the antibacterial activity of siwak’ crystal and extract were more potent against B. Melaninogenicus; it may be either that B. melaninogenicus was more susceptible than S. mutans or S. mutans was more virulent than B. melaninogenicus.

Abstrak :
Latar Belakang : Disbiosis mikrobiota usus dianggap berperan pada progresifitas NAFLD. Penelitian mengenai mikrobiota usus pada pasien NAFLD masih sedikit dan menunjukkan hasil yang berbeda. Tujuan : Mengetahui profil mikrobiota usus pada pasien NAFLD dengan derajat fibrosis hati. Metode : Penelitian menggunakan desain potong lintang, dengan menggunakan sampel pasien NAFLD di Rumah Sakit Cipto Mangunkusumo, periode waktu Maret – Juli 2018. Pemeriksaan sampel feses secara konsekutif dilakukan dengan menggunakan alat isolasi DNA (Tiangen) dan quantitative real-time polymerase chain reaction (Fast 7500) untuk menghitung jumlah mikrobiota dinyatakan dalam copy number DNA/gram feses (Bacteroides, Lactobacillus and Bifidobacteria). Sedangkan pemeriksaan fibrosis hati dengan menggunakan alat transient elastography (FibroScan® 502 Touch). Analisis statistik dilakukan menggunakan analisis bivariat dengan menggunakan uji chi-square. Hasil : Dari 60 pasien NAFLD, didapatkan 35 pasien dengan fibrosis non signifikan dan 25 pasien dengan fibrosis signifikan. Kebanyakan pasien merupakan penderita diabetes melitus (85%), dislipidemia (58,3%), obesitas (58,3%), dan obesitas sentral (90%). Didapatkan jumlah Bacteroides (483.000 kopi unit DNA/gram feses) paling banyak dibandingkan dengan Lactobacillus (100.800 kopi unit DNA/gram feses) dan Bifidobacteria  (12.110 kopi unit DNA/gram feses). Dari ketiga mikrobiota tersebut terdapat peningkatan bermakna proporsi Bacteroides pada kelompok fibrosis signifikan (81%) dibandingkan dengan fibrosis non signifikan (19%). Begitupula dengan Lactobacillus yang jumlahnya lebih banyak pada fibrosis signifikan. Sedangkan pada Bifidobacteria, proporsi pada fibrosis signifikan lebih rendah dibandingkan fibrosis non signifikan. Simpulan : Terdapat perubahan komposisi mikrobiota usus pada pasien NAFLD. Proporsi Bacteroides juga meningkat pada kelompok fibrosis signifikan. ......Background: Dysbiosis of the gut microbiota has been considered to have a role in NAFLD progression. However, there is still lack of studies regarding this phenomenon. Aim of the study: To find the difference of gut microbiota profile in NAFLD patient based on the stages of liver fibrosis. Patients and Methods: A cross sectional study was conducted at Dr. Cipto Mangunkusumo Hospital which is the largest tertiary refferal center hepatobiliary outpatient’s clinic. Human fecal samples from NAFLD patients who came to outpatient clinic were collected consecutively. The stool sample examination was performed using isolation DNA kit (Tiangen) and quantitative real-time polymerase chain reaction (Fast 7500) was used to measure total bacterial counts (Bacteroides, Lactobacillus and Bifidobacteria). Clinical and laboratory data, Food Frequency Questionare (FFQ) were also collected. The stage of fibrosis were diagnosed based on transient elastography (FibroScan® 502 Touch). Statistical analysis including bivariate analysis were performed using SPSS version 20. Results: Of 60 human fecal samples, there are 35 patients had non significant fibrosis and 25 patients had significant fibrosis and consist of 46.7% male and 53.3% female with the median age is 56 years old. Most patient have diabetes (85%) dyslipidemia (58.3%), obesity (58.3%), and central obesity (90%).  The Bacteroides count (483000) was higher when compared to Lactobacillus (100800) and Bifidobacteria (12110). Of these three microbiota, the proportion of Bacteroides was higher in significant fibrosis group when compared to non significant fibrosis group. Patient with significant fibrosis was also has a higher proportion of Lactobacillus compared to non significant fibrosis group (7000 vs 2050). In contrast, the proportion of Bifidobacteria was lower in significant fibrosis group (22) when compared to non significant fibrosis group (95). Conclusion: There is a dysbiosis of gut microbiota in NAFLD patients. Bacteroides as a gram-negative microbiota that produces LPS is significantly increased with fibrosis stage, that may play a role in NAFLD progression.

Abstrak :
Penyakit ginjal kronik (PGK) sudah menjadi masalah kesehatan global dengan prevalensi dan insidensi gagal ginjal yang meningkat dan memberikan prognosis buruk. Salah satu penyebab beratnya morbiditas pada PGK adalah terjadinya disbiosis mikroflora usus yaitu peningkatan flora patogen dibandingkan dengan flora normal pada pasien PGK dengan hemodialisis (PGK-HD). Studi ini bertujuan untuk mendapatkan pola mikrobiota usus pada pasien PGK dengan hemodialisis dengan metode kuantitatif PCR dengan pendekatan analisis ΔCt. Desain penelitian potong lintang dengan 71 subjek pasien PGK usia >18 tahun dengan hemodialisis rutin di RS. Umum Pusat Nasional Dr. Cipto Mangukusumo. Sampel berupa feses yang disimpan di suhu -20oC selama kurang dari setahun. Ekstraksi dan purifikasi DNA dengan teknik pengikatan silika dan metode buffer kit Exgene Stool DNA, Bioneer. Pengukuran konsentrasi DNA dengan spektrofotometer NanoVue dilanjutkan dengan standarisasi konsentrasi DNA dengan pengenceran sampel berdasarkan konsentrasi DNA terkecil. Pemeriksaan real-time q-PCR mesin Bioneer ExicyclerTM 96 dengan menggunakan 13 macam primer yaitu E.coli, Parasuterella excrementihominis, Prevotella, Bacteroides, Bifidobacterium, L.casei, L.acidophillus, Enterococcus faecalis, Enterococcus faecium, Clostridium difficile, Clostridium cocoides, Akkermansia muciniphila dan Beta-actin sebagai housekeeping gene (HKG). Hasil penelitian didapatkan dominasi mikrobiota usus E. coli dan rasio F/B pasien PGK-HD 2,76. Terdapat hubungan bermakna antara hipertensi dengan rasio F/B 9,35 4,0. Penelitian ini merupakan penelitian pertama tentang disbiosis mikrobiota usus pada pasien PGK dengan hemodialisis di Indonesia dengan menggunakan sampel feses dengan metode PCR kuantitatif pendekatan analisis ΔCt. Dengan diketahui profil mikrobiota usus pada PGK dapat dijadikan saran pemberikan suplementasi probiotik Bifidobacteria, sehingga diharapkan dapat meningkatkan konsentrasi mikrobiota filum Bacteroides. ......Chronic kidney disease (CKD) has become a global health problem with increasing in prevalence and incidence of kidney failure. One of the causes of severe morbidity in CKD is the occurrence of intestinal microflora dysbiosis, an increase in pathogenic flora compared to normal flora in CKD patients with hemodialysis (CKD-HD). This study aims to obtain patterns of gut microbiota in CKD patients on hemodialysis by quantitative PCR method with Ct approach analysis The design was a cross-sectional study with 71 CKD patients aged >18 years with routine hemodialysis in the hospital. General National Center Dr. Cipto Mangukusumo. Samples are feces that are stored at -20oC for less than one year. Extraction and purification of DNA with silica binding techniques using Exgene Stool DNA buffer kit method, Bioneer. Measurement of DNA concentration with the NanoVue spectrophotometer, followed by standardization of DNA concentration by diluting the sample based on the smallest DNA concentration. Real-time q-PCR examination of the Boneer ExicyclerTM 96 machine using 13 kinds of primers, namely E.coli, Parasuterella excrementihominis, Prevotella, Bacteroides, Bifidobacterium, L.casei, L.acidophillus, Enterococcus faecalis, Enterococcus faecium, Clostridium difficile, Clostridium cocoides, Akkermansia muciniphila and Beta-actin as a housekeeping gene (HKG). There was the dominance of the gut microbiota of E. coli and the F/B ratio of CKD-HD patients 2.76. There is a significant relationship between hypertension and the F/B ratio of 9.35 ± 4.0. This study is the first study on gut microbial dysbiosis in CKD patients on hemodialysis in Indonesia using stool samples using quantitative PCR method with Ct approach analysis. Knowing the gut microbiota profile in CKD, can be used as a suggestion for Bifidobacteria probiotic supplementation, as is expected to increase the concentration of the Bacteroides phylum microbiota.