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"Saat ini penyandang diabetes melitus tipe 2 (DMT2) sudah mencapai 415 juta dari seluruh penduduk dunia. Pengobatan yang tersedia masih memiliki banyak kelemahan sehingga dibutuhkan pengembangan obat-obat baru. Salah satu strategi pengobatan adalah dengan memperbaiki efek inkretin. Banyak fitofarmaka yang diketahui memiliki efek hipoglikemik. Ekstrak sambiloto sudah lama diketahui memiliki khasiat dalam pengobatan DMT2 dan digunakan secara tradisional di masyarakat. Studi ini bertujuan untuk mengetahui mekanisme kerja ekstrak sambiloto dalam kaitannya memperbaiki efek inkretin. Studi ini merupakan uji klinis tersamar ganda menggunakan desain cross over pada subjek normal dan prediabetes yang diberikan intervensi ekstrak sambiloto selama 14 hari dibandingkan dengan plasebo. Dilakukan pemeriksaan kadar GLP-1, insulin puasa, insulin 2 jam pascabeban, HOMA-IR, glukosa darah puasa, glukosa darah 2 jam pascabeban, enzim DPP-4, dan glycated albumin sebelum dan sesudah intervensi. Dilakukan analisis bivariat dan analisis lajur. Tujuh puluh tiga subjek (normal 38 dan prediabetes 35) dianalisis per protokol. Didapatkan perbaikan efek inkretin yang ditandai dengan peningkatan kadar GLP-1 yang bermakna setelah pemberian ekstrak sambiloto selama 2 minggu pada subjek prediabetes. Ekstrak sambiloto tidak menghambat enzim DPP-4 pada kelompok normal dan prediabetes. Berdasarkan analisis lajur didapatkan bahwa ekstrak sambiloto dapat berperan dalam metabolisme glukosa melalui jalur GLP-1 dan jalur resistensi insulin. Ekstrak sambiloto meningkatkan kadar GLP-1 tanpa menghambat enzim DPP-4 pada subjek prediabetes. Berdasarkan analisis lajur ekstrak sambiloto dapat memperbaiki resistensi insulin pada subjek prediabetes.

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There are 415 million type 2 diabetes mellitus (T2DM) patients in the world. Currently available antidiabetic drugs still have their own weakness so there is a need to develop better drugs. One of the newer strategies of diabetes therapy is through restoring the effect of incretin. Many phytochemicals have been known to have hypoglycemic effect. Sambiloto extract is known to have effect for T2DM therapy and has been used traditionally in the community. This study aims to discover the mechanism of sambiloto extract in restoring incretin effect. This study was a double blinded clinical trial using cross over design in normal and prediabetes subjects treated with sambiloto extract for 14 days compared with placebo. GLP- 1, fasting insulin, 2 hour postload insulin, HOMA-IR, fasting blood glucose, 2 hour postload blood glucose, DPP-4, and glycated albumin were measured before and after intervention. Bivariate and path analysis were applied to see the relationship. Seventy-three subjects (38 normal and 35 prediabetes) were analyzed according to protocol. Restoration of incretin effect was marked by significant increase of GLP-1 concentration after administration of sambiloto extract for 2 weeks in prediabetes subjects. Sambiloto extract did not inhibit DPP-4 enzyme in normal and prediabetes subjects. Path analysis had shown that sambiloto extract can affect glucose metabolism through GLP-1 pathway and insulin resistance pathway. Sambiloto extract increased GLP-1 concentration without inhibiting DPP-4 enzyme in prediabetes subjects. From path analysis showed that sambiloto extract can also ameliorate insulin resistance in prediabetes subjects."

"Karsinoma tiroid papiler (KTP) merupakan karsinoma tiroid yang paling sering ditemukan. Pada KTP terdapat driver mutation utama yakni BRAFV600E dan RAS. KTP dengan mutasi BRAFV600E umumnya menunjukkan perangai lebih agresif daripada RAS, keduanya harus dibedakan karena menentukan arah penatalaksanaan selanjutnya. Di Indonesia,pemeriksaan BRAFV600E dan RAS belum dilakukan rutin karena keterbatasan sumber daya. Tujuan penelitian ini adalah menganalisis aspek klinis, histopatologis dan ekspresi pERK1/2 sebagai prediktor diagnosis KTP dengan BRAFV600Eatau RAS. Penelitian ini menggunakan desain potong lintang yang dilakukan di RSUPN dr. Cipto Mangunkusumo pada bulan Maret 2022–Maret 2023. Subjek adalah pasien KTP yang menjalani tiroidektomi total sebanyak 222 pasien. Status mutasi diperiksa dengan PCR dan sekuensing DNA, menunjukkan 64 mutasi BRAFV600E, 42 mutasi RAS dan 116 non-BRAFV600E non-RAS. Ekspresi pERK1/2 diperiksa dengan imunohistokimia dan dihitung dalam satuan persentase. Terdapat hubungan antara karakteristik histopatologis (skor inti, kapsul, varian histopatologis, invasi jaringan lunak peritiroid dan metastasis kelenjar getah bening) dengan mutasi BRAFV600E. Terdapat hubungan antara varian histopatologis dengan mutasi RAS. Ekspresi pERK1/2 lebih tinggi secara bermakna pada BRAFV600E dan RAS, dibandingkan non-BRAFV600E non-RAS. Model prediksi BRAFV600E adalah skor inti 3 + tidak berkapsul + varian agresif + ekspresi pERK1/2 > 10%. Variabel skor inti 3, tidak berkapsul dan varian agresif masing-masing memberikan skor 1, sedangkan ekspresi pERK1/2 > 10% memberikan skor 2. Total skor 5 menunjukkan probabilitas 82% mutasi BRAFV600E. Model prediksi RAS adalah varian folikular + ekspresi pERK1/2 > 10%, masing-masing memberikan skor 1. Total skor 2 menunjukkan probabilitas 70% mutasi RAS. Selanjutnya dilakukan validasi internal dengan mengelompokkan total skor berdasarkan pertimbangan probabilitas dan spesifisitas. Kombinasi 1 (skor BRAFV600E 0–2dan skor RAS 0–1) menunjukkan proporsi non-BRAFV600E non-RAS lebih banyak ditemukan. Kombinasi 2 (skor BRAFV600E 0–2 dan skor RAS 2) atau RAS-like menunjukkan proporsi mutasi RAS secara bermakna lebih banyak ditemukan. Kombinasi 3 (skor BRAFV600E 3–5 dan skor RAS 0–1) atau BRAFV600E-like menunjukkan proporsi mutasi BRAFV600E secara bermakna lebih banyak ditemukan. Kombinasi 4 (skor BRAFV600E 3–5 dan skor RAS 2menunjukkan proporsi mutasi RAS secara bermakna lebih banyak ditemukan dibandingkan kelompok lainnya. Tata laksana standar atau eskalasi diusulkan berdasarkan stratifikasi risiko American Thyroid Association.

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Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma. PTC has two main driver mutations, namely BRAFV600E and RAS. PTC with BRAFV600E mutation is more aggressive than RAS and the two must be distinguished as they determine therapeutic strategy. In Indonesia, BRAFV600E and RAS examinations have not been carried out routinely due to limited resources. The aim of this study was to analyze the clinical profile, histopathological characteristics and pERK1/2 expression as a diagnostic predictor of PTC with BRAFV600E and RAS mutation. This study used a cross-sectional design conducted at RSUPN dr. Cipto Mangunkusumo (RSCM) from March 2022–March 2023. Subjects were 222 patients diagnosed with PTC who underwent total thyroidectomy. Mutation status was examined with PCR and DNA sequencing, consisting of 64 BRAFV600E mutations, 42 RAS mutations and 116 non-BRAFV600E non-RAS. pERK1/2 was examined using immunohistochemistry and calculated in percentage units. There was an association between histopathological characteristics (nuclear score, capsule, histopathological variants, peri-thyroidal soft tissue invasion and lymph node metastases) with BRAFV600E mutation. There was an association between histopathological variants and RAS mutation. The expression of pERK1/2 was significantly higher in BRAFV600E andRAS than non-BRAFV600E non-RAS. The BRAFV600E prediction model is a nuclear score of 3 + non-encapsulated + aggressive variant + pERK1/2 expression > 10%. Nuclear score of 3, non-encapsulated and aggressive variant variables each gave a score of 1, while expression of pERK1/2 > 10% gave a score of 2. The total score of 5 indicated 82% probability for BRAFV600E mutation. The predictive model for RAS is follicular variant + pERK1/2 expression > 10%. Each variable gave a score of 1. A total score of 2 indicated 70% probability for RAS mutation. Furthermore, internal validation was carried out by dividing the total score based on probability and specificity considerations. Combination 1 (BRAFV600E score 0–2 and RAS score 0–1) showed that non-BRAFV600E non-RAS were more commonly found. Combination 2 (BRAFV600E score 0–2 and RAS score 2) or RAS-like showed a significantly higher proportion of RASmutations. Combination 3 (BRAFV600E score 3–5 and RAS score 0–1) or BRAFV600E-like showed a significantly higher proportion of BRAFV600E mutations. Combination 4 (BRAFV600E score 3–5 and RAS score 2) showed a significantly higher proportion of RAS mutations than other groups. Standard management or escalation recommendation are proposed based on American Thyroid Association risk stratification."

"Kondisi hipertiroidisme berkorelasi dengan kejadian atherosclerosis cardiovascular disease (ASCVD). Hal ini dapat terjadi melalui jalur resistensi insulin, metabolisme lipid, dan inflamasi yang dapat menyebabkan disfungsi endotel. Sebaliknya, pemberian obat antitiroid seperti propiltiourasil (PTU) atau metimazol memiliki potensi untuk memperbaiki disfungsi endotel yang terjadi. PTU memiliki keunggulan dibandingkan metimazol dalam hal menghambat migrasi dan proliferasi otot polos vaskular. Studi ini bertujuan untuk mempelajari peran hormon tiroid dan pengobatannya pada pasien Graves terhadap penanda dini aterosklerosis.Studi ini merupakan uji klinis tersamar tunggal yang dilakukan di RSUPN Dr. Cipto Mangunkusumo (RSCM) pada pasien Graves baru yang diberikan PTU atau metimazol selama 3 bulan. Kedua kelompok diperiksakan HOMA-IR,LDL-R, NF-kB, sICAM-1, sVCAM-1 dan sE-selektin serta pulse wave velocity (PWV) dan carotid intima media thickness (cIMT) saat sebelum terapi, setelah terapi 1 bulan dan 3 bulan. Dilakukan uji Pearson atau Spearman untuk menilai korelasi antar variabel. Perubahan variabel dalam 3 bulan dinilai dengan uji repeated ANOVA. Perbedaan pada kelompok PTU dan metimazol dinilai dengan uji general linear model.Selama bulan Juli 2019 hingga Agustus 2020, didapatkan 36 pasien Graves baru. Pada uji korelasi didapatkan konsentrasi T4 bebas berkorelasi dengan sICAM-1(r = 0,41; p = 0,013) dan sVCAM-1 (r = 0,458; p = 0,005), begitu juga T3 total berkorelasi dengan sICAM-1 (r = 0,513; p = 0,001) dan sVCAM-1 (r = 0,567;p < 0,001). Pada tindak lanjut 3 bulan, didapatkan 24 subjek (13 kelompok PTU dan 11 kelompok metimazol) yang menyelesaikan pemeriksaan dan mencapai eutiroid. Pada kelompok PTU, didapatkan penurunan LDL-R (p = 0,017),sICAM-1 (p = 0,001), sVCAM-1 (p < 0,001) dan sE-selektin (p = 0,045). Pada kelompok metimazol terjadi penurunan hanya pada LDL-R (p = 0,011) dan sVCAM-1 (p = 0,001). Namun pada perbandingan kedua kelompok tidak berbeda bermakna. Parameter PWV dan cIMT juga tidak berbeda bermakna.Simpulan: Pada penelitian ini kondisi hipertiroid pasien Graves berkorelasi dengan peningkatan sICAM-1 dan sVCAM-1 sebagai penyebab aterosklerosis. Pemberian obat antitiroid dapat menurunkan LDL-R, sICAM-1, sVCAM-1 dan sE-selektin. PTU memiliki mekanisme yang berbeda dari metimazol dalam patofisiologi aterosklerosis. Akan tetapi, belum didapatkan bukti pada perubahan PWV dan cIMT

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Hyperthyroidism is correlated with atherosclerosis cardiovascular disease (ASCVD). The basic mechanisms are through insulin resistance, lipid metabolism, and inflammation resulted in endothelial dysfunction. On the other hand, antithyroid drugs such as propiltiourasil (PTU) or methimazole have the potential to improve the endothelial dysfunction. PTU is believed to have a better profile than methimazole in reducing smooth muscle cells migration and proliferation. This study aims to investigate the effect of thyroid hormone and its treatment in Graves’ disease to early marker of atherosclerosis.

This study is a single-blinded clinical trial conducted in dr. Cipto Mangunkusumo General Hospital (RSCM) to newly diagnosed Graves’ patient treated with PTU or methimazole for 3 months. Both groups were examined for LDL-R, NF-ĸB, sICAM-1, sVCAM-1, sE-selectin, pulse wave velocity (PWV) and carotid intima media thickness (cIMT) at baseline, after 1 month and 3 months treatment. Pearson or Spearman test was done to analyze correlation between tested variables. Repeated ANOVA test was done to analyze the changes in those variables during 3 months treatment. Difference between PTU and methimazole groups was analyzed with general linear model test.

From July 2019 to August 2020, 36 newly diagnosed Graves’ patients were included in the study. Correlation test showed free T4 concentration correlated to sICAM-1 (r = 0.41; p = 0.013) and sVCAM-1 (r = 0.458; p = 0.005), and total T3 also correlated to sICAM-1 (r = 0.513; p = 0.001) and sVCAM-1 (r = 0.567; p < 0.001). After 3 months follow up, 24 subjects (13 from PTU group and 11 from methimazole group) reached euthyroid state and included in the analysis. In PTU group, we found reduction in LDL-R (p = 0.017), sICAM-1 (p = 0.001),

sVCAM-1 (p < 0.001) and sE-selectin (p = 0.045). While in methimazole groups, we only found reduction in LDL-R (p = 0.011) and sVCAM-1 (p = 0.001). However, after comparing both groups, the differences were not statistically significant. We found no significant changes in PWV and cIMT parameter.

In conclusions, this study found that hyperthyroidism in Graves’ patient correlated with increase in sICAM-1 and sVCAM-1, which are the early markers of atherosclerosis. Antithyroid drugs can lower LDL-R, sICAM-1, sVCAM-1 and sE-selectin. PTU had a different mechanism in pathophysiology of atherosclerosis compared to methimazole. However, we found no evidence in PWV and cIMT changes"