EVALUASI EFEK ANTI-DIABETES MELITUS EKSTRAK TERPURIFIKASI Andrographis paniculata (Burm. f.) Nees DAN ANDROGRAFOLID DENGAN PARAMETER INDEKS HOMA-IR

Diabetes mellitus type 2 was induced by high fat diet and fructose. The insulin resistance and hyperinsulinemia compensatory can be measured by index homeostatic model assessment – insulin resistance (HOMA-IR). Andrographis paniculata (Burm. f.) Nees is a traditional plant can be used to treat diabetes mellitus and the main active compound of this plant is Andrographolide. The objective of this study is to evaluate the effect of purified extract of Andrographis paniculata (Burm. f.) Nees and andrographolide on HOMA-IR index of High fat diet and fructose induced Wistar Rats. This study is quasi-experimental and data analysis was using Kruskal-Wallis test. The result showed that purified extract of Andrographis paniculata and andrographolide decreased HOMA-IR index. Purified extract of Andrographis paniculata 1303,8 mg/kg decreased HOMA-IR index by 82,05 %.Diabetes mellitus (DM) tipe 2 dipicu oleh diet tinggi lemak dan fruktosa (DTLF) dan diawali dengan resistensi insulin dan hiperinsulinemia kompensatori, yang dapat dilihat dari indeks homeostatic model assessment – insulin resistance (HOMA-IR). Salah satu tanaman tradisional yang dapat digunakan untuk mengatasi DM adalah Andrographis paniculata (Burm. f.) Nees, dengan senyawa aktif utama andrografolid. Penelitian ini bertujuan untuk mengetahui efek ekstrak terpurifikasi A. paniculata dan andrografolid pada indeks HOMA-IR tikus Wistar dengan DTLF. Penelitian bersifat kuasi-eksperimental dan analisis data menggunakan uji Kruskal-Wallis. Hasil menunjukkan bahwa ekstrak terpurifikasi A. paniculata dan andrografolid dapat menurunkan indeks HOMA-IR, dan penurunan terbesar (82,05%) dihasilkan oleh ekstrak terpurifikasi A. paniculata dengan dosis 1303,8 mg/kgBB

EFEK EKSTRAK TERPURIFIKASI Andrographis paniculata (Burm. f.) Nees DAN ANDROGRAFOLID TERHADAP INDEKS HOMA-IR TIKUS PUTIH (Rattus norvegicus) GALUR WISTAR DENGAN DIET TINGGI LEMAK DAN FRUKTOSA

Background: Early stage of type 2 diabetes mellitus pathogenesis includes insulin resistance, shown by increment of homeostasis model assessment � insulin resistance (HOMA-IR) index. A. paniculata is known to have antihyperglycemic effect, but its effect on HOMA-IR index of high fat and fructose fed Wistar rats is unknown. Objectives: To see whether A. paniculata purified extract and andrographolide modify HOMA-IR index of high fat and fructose fed Wistar rats, and determine form and dosage that yields the best result. Method: Thirty eight Wistar rats were divided into 7 groups, ND (given standard chow diet for 55 days), HFFD (given combination of 80% standard chow, 15% lard, 5% duck egg yolk, and fructose 180 mg/100 gBB for 55 days), HFFD-Met (HFFD for 55 days, metformin 45 mg/kgBB for the last 5 days), HFFD-E1 and E2 (HFFD for 55 days, A. paniculata purified extract 434,6 mg/kgBB and 1.303,8 mg/kgBB for the last 5 days), HFFD-A1 and A2 (HFFD for 55 days, andrographolide 1,5 mg/kgBB and 4,5 mg/kgBB for the last 5 days). Sera were collected on the 55th day to measure the fasting glucose and insulin concentrations, and to calculate HOMA-IR index. The three data were analysed using Kruskal-Wallis and Mann-Whitney tests. Results: Mean fasting insulin concentration of HFFD-E1 and E2 (0,40 ng/ml) is lower than those given andrographolide. Mean fasting glucose concentration of HFFD-E2 (73,40 mg/dl) is lower than other treatment groups, even HFFD-Met (74,33 mg/dl) which is the positive control group. Mean HOMA-IR index of HFFD-E2 (0,07) is lower than other treatment groups except HFFD-Met (0,06). Conclusion: Both A. paniculata purified extract and andrographolide reduces HOMA-IR index of high fat and fructose fed Wistar rats. The greatest HOMA-IR index reduction is yielded by A. paniculata purified extract with the dosage of 1.303,8 mg/kgBB

Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity

In addition to susceptibility to infections, conventional primary immunodeficiency disorders (PIDs) and inborn errors of immunity (IEI) can cause immune dysregulation, manifesting as lymphoproliferative and/or autoimmune disease. Autoimmunity can be the prominent phenotype of PIDs and commonly includes cytopenias and rheumatological diseases, such as arthritis, systemic lupus erythematosus (SLE), and Sjogren's syndrome (SjS). Recent advances in understanding the genetic basis of systemic autoimmune diseases and PIDs suggest an at least partially shared genetic background and therefore common pathogenic mechanisms. Here, we explore the interconnected pathogenic pathways of autoimmunity and primary immunodeficiency, highlighting the mechanisms breaking the different layers of immune tolerance to self-antigens in selected IEI

Peripheral Blood Lymphocyte Phenotype Differentiates Secondary Antibody Deficiency in Rheumatic Disease from Primary Antibody Deficiency

The phenotype of primary immunodeficiency disorders (PID), and especially common variable immunodeficiency (CVID), may be dominated by symptoms of autoimmune disorders. Furthermore, autoimmunity may be the first manifestation of PID, frequently preceding infections and the diagnosis of hypogammaglobulinemia, which occurs later on. In this case, distinguishing PID from hypogammaglobulinemia secondary to anti-inflammatory treatment of autoimmunity may become challenging. The aim of this study was to evaluate the diagnostic accuracy of peripheral blood lymphocyte phenotyping in resolving the diagnostic dilemma between primary and secondary hypogammaglobulinemia. Comparison of B and T cell subsets from patients with PID and patients with rheumatic disease, who developed hypogammaglobulinemia as a consequence of anti-inflammatory regimes, revealed significant differences in proportion of naïve B cells, class-switched memory B cells and CD21low B cells among B cells as well as in CD4+ memory T cells and CD4+ T follicular cells among CD4+ T cells. Identified differences in B cell and T cell subsets, and especially in the proportion of class-switched memory B cells and CD4+ T follicular cells, display a considerable diagnostic efficacy in distinguishing PID from secondary hypogammaglobulinemia due to anti-inflammatory regimens for rheumatic disease