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"In this volume, international experts in the field discuss the pathogenetic, diagnostic, preventive and possible therapeutic relevance of inflammation in atherogenesis. This book is intended for researchers and physicians in the fields of vascular biology, immunology and atherosclerosis."

"Latar belakang : Inflamasi pada hemodialisis (HD) berhubungan dengan terjadinya kontak darah dengan membran dialisis, cairan dialisat, akses vaskuler dan infeksi. Peningkatan sitokin pro-inflamasi berperan penting terhadap terjadinya aterosklerosis selain itu inflamasi berakibat anoreksia dan kondisi hiperkatabolik yang menyebabkan malnutrisi. Keadaan ini disebut sebagai Sindrom Malnutrisi-Inflamasi-Aterosklerosis. Karakteristik HD di Indonesia berbeda dengan negara maju, perbedaan tersebut terkait penggunaan dialyzer pakai ulang dan tipe low-flux, belum menggunakan dialisat ultrapure dan dosis HD yang tidak adekuat.Tujuan : Melihat beda rerata antara Skor-MI, hsCRP dan sTNFR-1 pada pasien HD yang mengalami aterosklerosis dan yang tidak aterosklerosis.Metode Penelitian : Desain studi potong lintang pada pasien HD yang dalam keadaan stabil yang sudah menjalani HD antara 3 bulan sampai 5 tahun di RSUP Fatmawati. Jumlah subyek 60 orang yang dikumpulkan dalam kurun waktu Desember 2013 sampai dengan Februari 2014. Pemeriksaan hsCRP dan sTNFR-1 sebagai biomarker inflamasi, untuk menentukan status nutrisi menggunakan skor malnutrisi-inflamasi(Skor-MI) dan pemeriksaan USG doppler arteri Karotis untuk menentukan penebalan intima-media(CIMT). Analisis statistik dengan uji T dan uji Mann-Whitney.Hasil : Penelitian ini menunjukkan Skor-MI pada kelompok yang CIMT positif (aterosklerosis) memiliki nilai median lebih tinggi dibandingkan dengan kelompok yang non aterosklerosis (7 vs 5). Sedangkan kadar sTNFR-1 memiliki nilai median CIMT positif (3.48) lebih rendah dibandingkan CIMT negatif (12,126 vs 11,657). Kadar hsCRP pada kelompok CIMT positif memiliki nilai rata-rata lebih tinggi dibandingkan dengan kelompok dengan CIMT yang negatif (3.48 vs 5.32). Dari ketiga variabel tersebut tidak ada beda rerata (p>0,05).Kesimpulan : Tidak terdapat beda rerata antara Skor-MI, hsCRP dan sTNFR-1 pada pasien HD yang mengalami aterosklerosis dan yang tidak aterosklerosis.

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Background: Inflammation in hemodialysis is associated with blood contact with dialysis membrane, dialysate solution, vascular access and infection. Increment of pro-inflammatory cytokine plays important role in atherosclerosis development. Inflammation also causes anorexia and hypercatabolism state leading to malnutrition. This condition is called malnutrition-inflammation-atherosclerosis syndrome. Hemodialysis characteristics in Indonesia is different with those in developed countries. Those differences are associated with reuse dialyzer, low flux hemodialysis, inadequate dose of hemodialysis, and unavailability of ultrapure dialysate.Aim: To determine the mean difference between MI score, hsCRP and sTNFR-1 in hemodyalisis patients with atherosclerosis and non-atherosclerosis.Methods: This is a cross-sectional study which has involved hemodialysis patients who underwent HD between 3 months to 5 years in Fatmawati Central Hospital. There are 60 subjects collected from December 2013 until February 2014. hsCRP and soluble TNFR-1 were used as inflammation biomarker, MI score was used to assess nutritional status. and carotid doppler ultrasonography was used to assess carotid intima media thickness. This study used T-test and Mann-Whitney for statistical analysis.Results: Median score for malnutrition-inflammation score in atherosclerotic group is higher than non atherosclerotic group (7 vs 5), while the median sTNFR-1 in atherosclerotic group is lower than non atherosclerotic group (12,126 vs 11,657). Mean hsCRP in atherosclerotic group is higher than non atherosclerotic group (3.48 vs 5.32). There are no mean differences of all those three variables (p>0.05).Conclusion: No mean differences between MI-score, hsCRP, and sTNFR-1 with atherosclerotic and non-atherosclerotic in HD patients."

"Adi Haber's thesis summarises the use of a new entity, the corrole, to combat one of the major cardiovascular diseases, atherosclerosis. She examines the effects of three rationally designed corrole-metal complexes on some of the many variables which contribute to the development of atherosclerosis. There is a focus on both the "bad" and "good" cholesterol carriers, LDL and HDL. Adi Haber proceeds from basic findings in pure chemistry through biochemical and cell culture tests to in vivo examinations. The work in this thesis shows that corroles are highly efficient both for early and late treatment of atherosclerosis in animals. These results will pave the way for ongoing regulated preclinical studies focussed on the development of metallocorroles as potential drugs for treating cardiovascular diseases."

"Ultrasound and carotid bifurcation atherosclerosis provides a comprehensive overview of the most recent advancements in instrumentation, imaging techniques including the use of contrast enhancement agents, plaque image analysis and its automation, elastography and plaque motion analysis; also, the use of ultrasonic and other biomarkers in the detection of the high risk cardiovascular individual. Finally, it deals with the application of IVUS, TCD and carotid plaque characterization in clinical practice and in stroke risk stratification. "

"Atherosclerosis is a chronic inflammatory disorder involving innate and adaptive immunity process. Effector T cell (Teff) responses promote atherosclerotic disease, whereas regulatory T cells (Tregs) have been shown to play a protective role against atherosclerosis by down-regulating inflammatory responses which include multiple mechanisms. Compelling experimental data suggest that shifting the Treg/Teff balance toward Tregs may be a possible therapeutic approach for atherosclerotic disease, although the role of Tregs in human atherosclerotic disease has not been fully elucidated. In this review, we discuss recent advances in our understanding of the roles of Tregs and Teffs in experimental atherosclerosis, as well as human coronary artery disease.

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Aterosklerosis merupakan suatu proses peradangan kronik, yang melibatkan imunitas alamiah dan adaptif. Respon sel T efektor (Teff) berperan dalam mempercepat terjadinya aterosklerosis. Adapun sel T regulator (Treg), mempunyai peran sebagai komponen pelindung dalam proses aterosklerosis melalui modulasi respon inflamasi yang melibatkan berbagai mekanisme. Dari berbagai studi eksperimental menunjukkan bahwa perubahan keseimbangan antara Treg/Teff dengan polarisasi ke arah Treg dapat menjadi pendekatan terapeutik pada aterosklerosis, meskipun peran Treg dalam studi klinis belum sepenuhnya dapat dijelaskan. Dalam tinjauan pustaka ini, kami akan menelaah berbagai perkembangan dan pemahaman terkini mengenai peran Treg dan Teff dalam studi eksperimental dan klinis aterosklerosis."

"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"

"The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage. Cells in innate immune system produce ROS, such as superoxide and hydrogen peroxide, which aimed at killing pathogens. Long-term inflammation process increases ROS production, causing oxidative stress which leads to endothelial dysfunction. Endothelial function is to regulate blood vessel tone and structure. When inflammation lasts, NO bioavailability decreases, disrupting its main function as vasodilator, so that blood vessels relaxation and vasodilatation are absent. Effector T cells and regulatory lymphocytes, part of the adaptive immune system, plays role in blood vessels constriction in hypertension. Signals from central nervous system and APC activates effector T lymphocyte differentiation and accelerate through Th-1 and Th-17 phenotypes. Th-1 and Th-17 effectors participate in inflammation which leads to increased blood pressure. One part of CD4+ is the regulatory T cells (Tregs) that suppress immune response activation as they produce immunosuppressive cytokines, such as TGF-I and IL-10. Adoptive transfer of Tregs cells can reduce oxidative stress in blood vessels, endothelial dysfunction, infiltration of aortic macrophages and T cells as well as proinflammatory cytokine levels in plasma circulation.

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Sistem imun, proses inflamasi serta hipertensi saling berkaitan. Sistem imun alamiah dan adaptif memicu proses inflamasi, mengakibatkan peningkatan tekanan darah yang merangsang kerusakan organ. Sel pada sistem imun alamiah memproduksi ROS seperti superoksida dan hidrogen peroksida yang bertujuan membunuh patogen. Proses inflamasi jangka-panjang meningkatkan produksi ROS, menyebabkan stress oksidatif, mengakibatkan disfungsi endotel. Endotel berfungsi mengatur tonus dan struktur pembuluh darah. Saat inflamasi, bioavaibilitas NO menurun, mengganggu fungsi utamanya, sehingga mencegah relaksasi dan vasodilatasi pembuluh darah. Sel T efektor dan limfosit regulatori, bagian dari sistem imun adaptif, berperan pada konstriksi pembuluh darah pada hipertensi. Sinyal dari sistem saraf pusat dan APC mengaktivasi diferensiasi limfosit T efektor, dan mempercepat melalui Th-1 dan fenotip Th-17. Efektor Th-1 dan Th-17 berpartisipasi dalam inflamasi, mengakibatkan peningkatan tekanan darah. Salah satu bagian CD4+ adalah regulatory T cells (Tregs) yang menekan aktivasi respons imun dengan memproduksi sitokin imunosupresif seperti TGF-β dan IL-10. Transfer adoptif dari sel Tregs menurunkan stres oksidatif pada pembuluh darah, disfungsi endotel, infiltrasi dari makrofag aorta dan sel T serta kadar sitokin proinflamasi dalam sirkulasi plasma"