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"Phospholipid is a lipoprotein particle that contains a specific protein called apolipoprotein. Apolipoprotein is the outer, exposed portion of negatively charged phos-pholipids (aiiionic phospholipids), which functions as enzyme or specific protein binding agents. The cell wall is formed by phospholipids, while apolipoproteins in the outer portion of the cell wall function as uptake receptors."

"Latar belakang: Imunotoksin adalah salah satu bentuk terapi target pada kanker berupa konjugasi antara antibodi monoklonal dengan molekul toksin Antibodi menghantarkan toksin ke sel kanker dan menyebabkan kematian sel. Pada penelitian ini, toksin mitokondria asam bongkrek dikonjugasikan dengan antibodi anti-CD3 menjadi senyawa konjugat asam bongkrek-antibodi anti-CD3, dan digunakan SMDT sebagai model uji spesifisitas. Tujuan: Penelitian ini bertujuan untuk mensintesis senyawa konjugat antara asam bongkrek dengan antibodi monoklonal anti-CD3 dan uji spesifisitas secara in-vitro pada SMDT. Metode: Uji in-silico dilakukan untuk memprediksi situs konjugasi. Sintesis imunotoksin asam bongkrek-antibodi anti-CD3 dilakukan secara kimiawi menggunakan penaut EDC.HCl/Sulfo-NHS. SMDT digunakan sebagai model uji spesifisitas. Hasil: Molecular docking menunjukkan bahwa asam amino lisin, asparagin dan glutamin dari Fc IgG2a berinteraksi secara kovalen dengan gugus karboksilat dari asam bongkrek. Serapan senyawa konjugat pada panjang gelombang 280 nm dan 260 nm menunjukkan adanya serapan protein dan asam bongkrek. Inkubasi SMDT dengan senyawa konjugat menunjukkan jumlah sel hidup yang lebih tinggi dibandingkan dengan inkubasi asam bongkrek (p<0.05) ataupun dengan antibodi anti-CD3 (p<0.05). Kesimpulan: Uji in-silico menunjukkan adanya interaksi antara gugus karboksilat dari asam bongkrek dengan gugus amina primer dari imunoglobulin. Uji in-vitro senyawa konjugat menunjukkan efek sitotoksik lebih rendah dibandingkan dengan asam bongkrek maupun antibodi anti-CD3.

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Background: Immunotoxin is a form of targeted therapy in cancer in the form of conjugation between monoclonal antibodies and toxins. Antibodies will deliver toxins to cancer cells and cause cell death. In this study, mitochondrial toxin bongkrekic acid was conjugated with anti-CD3 monoclonal antibodies into anti-CD3 monoclonal antibody-bongkrekic acid conjugate, and PBMC was used as a specificity test model.

Objective: This study aims to synthesize conjugate between bongkrekic acid with anti-CD3 monoclonal antibodies and in-vitro specificity tests on PBMC. Method: An in-silico test was performed to predict the conjugation site. The synthesis of anti-CD3 monoclonal antibody-bongkrekic acid was carried out chemically using EDC.HCl/Sulfo-NHS crosslinker. PBMC was used as a specificity test model.

Results: Molecular docking showed that the amino acids lysine, asparagine, and glutamine from Fc IgG2a interact covalently with the carboxylic group of bongkrekic acid. The spectroscopy measurement of conjugate compounds at wavelengths of 280 nm and 260 nm indicates the absorption of proteins and bongkrekic acid. PBMC incubation with conjugate compounds showed a higher number of living cells compared to bongkrekic acid (p<0.05) or with anti-CD3 antibodies (p < 0.05).

Conclusion: In-silico studies show an interaction between the carboxylic group of bongkrekic acid and the primary amine group of immunoglobulin. In-vitro assays of conjugate compounds showed lower cytotoxic effects compared to bongkrekic acid and anti-CD3 antibodies."

"Latar belakang: PLI awalnya dilakukan pada tahun 1981 untuk mengatasi kasus-kasus klinis seperti keguguran berulang dan meningkatkan keberhasilan In-Vitro Fertilization (IVF) di beberapa negara. PLI menstimulasi dan mengaktifkan imunotoleran pada sistem imun ibu. Toleransi imun pada ibu dibutuhkan untuk terjadinya konsepsi. Keseimbangan Th1/Th2 dan Treg berperan penting dalam kehamilan. Kejadian ASA pada pasangan infertil sebanyak 10-30%. Keberhasilan PLI dalam mengatasi kasus-kasus klinis dan menurunkan ASA telah terbukti, namun mekanisme imun yang terjadi setelah pemberian PLI belum diketahui. Penelitian ini ingin mengetahui mekanisme imun yang terjadi setelah PLI pada perempuan dengan infertilitas yang tidak terjelaskan dengan melakukan analisis terhadap ASA, IL6, IL10, IFNγ, IDO, dan populasi sel Treg CD4⁺CD25⁺Foxp3⁺. Metode: Desain penelitian ini adalah analitik observasional. Penelitian dilaksanakan di RSIA Sayyidah Jakarta pada bulan Juni 2018 s.d April 2019. Sampel penelitian ini adalah 16 perempuan infertil tidak terjelaskan dengan titer ASA > 1:128. Hasil: PLI dapat menurunkan ASA. Rasio kenaikan persentase sel Treg  CD4⁺CD25⁺FoxP3⁺ yang tinggi setelah 6 kali PLI lebih besar (50%) dibandingkan 3 kali PLI (20%) namun belum ditemukan pengaruhnya secara bermakna terhadap frekuensi PLI. Kenaikan rasio IL10 post/awal penelitian yang tinggi lebih besar (75%) pada kelompok dengan persentase penurunan titer ASA sedikit dibandingkan pada kelompok persentase penurunan titer ASA banyak (11,1%), hal ini berbanding terbalik dengan hipotesis. Tidak terdapat perbedaan bermakna rasio IL6 (p 0,089), IFNγ (p 0,959), dan IDO post/awal penelitian dengan persentase penurunan titer ASA setelah PLI. Kenaikan IFNγ yang tinggi diikuti oleh kenaikan rasio IDO post/awal penelitian dan kenaikan persentase populasi sel Treg CD4⁺CD25⁺FoxP3^+. Simpulan: PLI menurunkan ASA pada perempuan dengan infertilitas tidak terjelaskan. Terdapat kenaikan rasio populasi sel Treg CD4⁺CD25⁺FoxP3⁺ setelah PLI namun kenaikan rasio populasi sel Treg CD4⁺CD25⁺FoxP3⁺ belum ditemukan pengaruhnya secara bermakna terhadap frekuensi PLI. Tidak didapatkan peningkatan IL10, IL6, IFNγ dan kadar IDO setelah penurunan ASA pada perempuan infertilitas tidak terjelaskan yang mendapatkan PLI. Terdapat korelasi antara kadar IFNγ, IDO, dan populasi sel Treg

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Background: PLI is firstly introduced in 1981 to treat clinical cases such as recurrent misscarriage or increase success rate of IVF in various countries. PLI stimulate and activate immunotolerancy to maternal immune systems. Maternal immune tolerancy is required for conceptions. Th1 and Th2 balance ratio and Treg play role during pregnancy. ASA occured in 10-30% of infertility couples. PLI successness to overcome clinical cases and decrease ASA has been demonstrated. However, immune mechanism after PLI treatment were remained unclear. This research aim to understand immune mechanism after PLI in female with unexplained infertility by analyzed ASA, IL6, IL10, IFNγ, IDO, Treg CD4⁺CD25⁺Foxp3⁺ cells populations.

Methods : This research using observational analysis. The research were conducted in RSIA Sayyidah Jakarta from Juni 2018 to April 2019. Samples were 16 female with unexplained infertility with ASA titre > 1:128.

Result: PLI can decrease ASA. Increase ratio of Treg CD4⁺CD25⁺FoxP3⁺ percentages was higher after 6 times of PL1 (50%) compared to 3 times of PLI (20%). However no significant effect to PLI frequencies observed. Increase ratio of IL10 at post/early research was higher (75%) in groups with moderate decrease of ASA titre compared to groups with significant decrease of ASA titre (11%), this is contradictive to the hypothesis. No significant differences of IL6 (p 0.089), IFNγ (p 0.959), and IDO at post/early of this research with decrease ASA titre percentages after PLI. A significant increase of IFNγ were followed by increase ratio of IDO at post/early research and increase percentages of Treg CD4⁺CD25⁺FoxP3⁺.

Conclusion: PLI can decrease ASA in female with unexplained infertility. Increase ratio of Treg CD4⁺CD25⁺FoxP3⁺ populations were observed after PLI. However, the effect to PLI frequencies were not observed. No increase of IL10, IL6, IFNγ dan IDO level after decrease of ASA in female with unexplained infertility that received PLI. Correlations of IFNγ , IDO, and Treg populations was founded."

"Epidermal growth factor receptor variant III (EGFRvIII) is a mutant EGFR lacking 267 amino acids (exon-2 throught 7) within its extracellular domain, resulting in the formation of a new epitope as a tumor-Antibodies ..."

"Translational strategies for development of antibody-based therapeutics should allow understanding of the relationship between the ?unit dose? and ?unit effect? with respect to both beneficial and deleterious effects from early stages of development. The flow of information from later to earlier stages of development should provide opportunities to facilitate selection of more effective novel and next-generation drug candidates. Selection and evaluation of relevant biomarkers in early preclinical development in "relevant" animal models should allow for identifying potential risks to humans and establishing safe First-In-Human (FIH) dosing strategies. Hence, integration of knowledge with respect to target antigen properties such as antigen distribution, expression profile, kinetic properties, target pharmacology, antigen isoforms and pharmacological redundancy in health and disease, as well as antibody design criteria, such as antibody isotype, affinity, PK/PD and safety is a critical necessity for the design of effective translational strategies. Additionally, these factors will further offer critical differentiating characteristics for next-generation antibodies, and novel technologies prove instrumental in generation of biosuperior antibody candidates for market entry. This book will examine many important considerations necessary for the design of effective translational strategies during the development of antibody-based therapeutics."

"Aterosklerosis sampai saat ini merupakan penyebab utama morbiditas dan mortalitas di negara maju. Meskipun modifikasi faktor risiko di negara maju telah dapat menurunkan kekerapan aterosklerosis namun penurunan ini mulai menunjukkan grafik yang mendatar. Keadaan ini merangsang para peneliti untuk mencari faktor pajanan lingkungan termasuk faktor infeksi yang dapat mempengaruhi proses aterosklerosis. Telah dilakukan penelitian potong lintang dari bulan Maret 1998 sampai Agustus 1998 terhadap 122 orang pasien yang secara klinis menunjukkan penyakit jantung koroner yang menjalani kateterisasi jantung, terdiri dari 92 orang laki-laki dan 30 orang perempuan dengan rerata umur 55 tahun. Pasien diperiksa secara klinis dan laboratorium (gula darah, kolesterol, trigliserida dan antibodi terhadap C.pneumoniae, Cytomegalovirus dan H.pylori). Pada penelitian ini didapatkan perbedaan kadar kolesterol, trigliserida dan HDL antara kelompok stenosis koroner dan non stenosis. Sedangkan kadar antibodi C.pneumoniae, Cytomegalovirus, H.pylori tidak berbeda bermakna. Penelitian ini belum dapat menyimpulkan pengaruh antibodi terhadap aterosklerosis karena pada kelompok non stenosis tidak dapat disingkirkan kemungkinan terjadinya aterosklerosis mengingat rerata umur subyek penelitian 55 tahun. Penelitian mengenai interaksi infeksi dengan risiko tradisional serta gender dan nutrisi diperlukan untuk mendapat jawaban yang lebih jelas tentang pengaruh infeksi terhadap aterosklerosis. (Med J Indones 2002; 11: 211-4)

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Atherosclerosis is still the chief cause of morbidity and mortality in developed nations. Even though in developed nations the modification of risk factors is able to reduce the prevalence rate of atherosclerosis, such reduction is starting to slow down. Such condition has stimulated researchers to identify environmental exposure, including infection, that can influence the process of atherosclerosis. This cross sectional study was conducted from March to August 1998, on 122 patients that clinically demonstrate coronary heart disease and have underwent cardiac catheterization, 92 males and 30 females with an average age of 55 years. Patients undergo clinical and laboratory evaluation (blood glucose, cholesterol, triglyceride, and antibody for C.pneumoniae. Cytomegalovirus, and H.pylori). We found a significant difference in cholesterol, triglyceride, and HDL levels in those with coronary stenosis and those without. However, we did not find a significant difference in the levels of C.pneumoniae, Cytomegalovirus, and H.pylori antibodies. This study is unable to conclude the influence of these antibodies on atherosclerosis, since in the non-stenosis group, we cannot eliminate the possibility of atherosclerosis, since the average age of study subject is 55 years. Studies on the interaction between infection and traditional risk factors as well as gender and nutrition is needed to find a clear answer of the influence of infection in atherosclerosis. (Med J Indones 2002; 11: 211-4)"

"Pendahuluan: Epilepsi merupakan salah satu kelainan neurologis terbanyak di dunia, kurang lebih 20-30% diantaranya merupakan epilepsi resistan obat. Salah satu penyebab epilepsi resistan obat adalah autoimun, yang diperantari antibodi saraf. Antibodi saraf yang paling sering ditemukan dan diteliti adalah antibodi anti N-Methyl-D-Aspartate (NMDAR). Diagnosis pasti epilepsi autoimun adalah ditemukannya antibodi saraf di serum atau cairan serebrospinal (CSS), namun saat ini ketersediaanya terbatas dan harganya cukup mahal di Indonesia. Skor Antibody Prevalence in Epilepsy and Encephalopathy 2 (APE2) dan Antibody Contributing to Focal Epilepsy Signs and Symptoms (ACES) merupakan dua piranti klinis yang dapat digunakan untuk menduga adanya antibodi saraf, namun belum ada penelitiannnya di Indonesia. Tujuan: Penelitian ini adalah uji diagnostik untuk menilai kemampuan APE2 dan ACES dalam menduga adanya antibodi saraf anti NMDAR di serum pasien epilepsi resisten obat. Metode: Pasien epilepsi resistan obat yang datang ke Poli Neurologi Anak Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo Jakarta dan Rumah Sakit Umum Daerah dr. Soetomo Surabaya pada bulan Maret hingga Agustus 2023 dinilai menggunakan APE2 dan ACES lalu diperiksa serum antibodi anti NMDAR. Hasil: Didapatkan 90 subyek penelitian yang memenuhi kriteria inklusi dan eksklusi penelitian. Antibodi NMDAR serum ditemukan pada 10 dari mereka. Skor APE2 memiliki sensitivitas 60%, spesifisitas 82,5%, PPV 30%, NPV 94,3%, LR+ 3,43, dan LR- 0,48. Poin skor APE2 yang memiliki nilai bermakna adalah perubahan status mental (p 0,042) dan gejala prodormal sebelum kejang (p 0,005). Skor ACES memiliki sensitivitas 85,71% spesifisitas 72,22%, PPV 37,5%, NPV 96,3%, LR+ 3,08, dan LR- 0,198. Poin skor ACES yang memiliki nilai bermakna adalah gangguan kognitif (p 0,033) dan gangguan bicara (p 0,028). Pada kejang fokal, APE2 memiliki nilai sensitivitas, PPV, NPV dan LR+ yang lebih rendah namun spesifisitas dan LR- yang lebih tinggi dibandingkan dengan ACES. Kesimpulan: Skor APE2 kurang sensitif namun cukup spesifik dengan NPV yang tinggi. Skor ACES cukup sensitif dan spesifik dengan NPV yang tinggi. Keduanya dapat digunakan untuk skrining awal epilepsi terutama bila ada gejala perubahan status mental, gejala prodormal virus, gangguan kognitif dan gangguan bicara sebelum atau saat awal awitan kejang. Diperlukan penelitian lanjutan untuk menilai antibodi saraf lain, dengan pemeriksaan antibodi di CSS dan tidak terbatas pada epilepsi resisten obat saja serta yang awitan kejangnya dibawah 1 tahun.

Kata kunci: ACES, APE2, epilepsi autoimun, epilepsi resisten obat, NMDAR

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Epilepsy is one of the most common neurological disorders in the world, approximately 20-30% of which are drug-resistant epilepsy. One cause of drug-resistant epilepsy is autoimmune disease, mediated by neural antibodies. The most frequently found and studied neural antibody is the anti-N-Methyl-D-Aspartate (NMDAR) antibody. The definitive diagnosis of autoimmune epilepsy is the discovery of neural antibodies in serum or cerebrospinal fluid (CSF), but currently their availability is limited and the price is quite expensive in Indonesia. The Antibody Prevalence in Epilepsy and Encephalopathy 2 (APE2) score and Antibody Contributing to Focal Epilepsy Signs and Symptoms (ACES) are two clinical tools that can be used to suspect the presence of neural antibodies, but there has been no research in Indonesia. Purpose: This research is a diagnostic test to assess the ability of APE2 and ACES to predict the presence of anti-NMDAR neural antibodies in the serum of drug-resistant epilepsy patients. Methods: Drug-resistant epilepsy patients who seek treatment at the Pediatric Neurology Outpatient clinic at the National Central General Hospital, dr. Cipto Mangunkusumo Jakarta and the Regional General Hospital dr. Soetomo Surabaya from March to August 2023 were assessed using APE2 and ACES, then checked for serum anti NMDAR antibody. Results: There were 90 research subjects who met the research inclusion and exclusion criteria. Serum NMDAR antibodies were found in 10 of them. The APE2 score has a sensitivity of 60%, specificity of 82.5%, PPV of 30%, NPV of 94.3%, LR+ 3.43, and LR- 0.48. In this study, the APE2 score points that had significant values were changes in mental status (p 0.042) and prodromal symptoms before seizures (p 0.005). The ACES score has a sensitivity of 85.71%, a specificity of 72.22%, PPV 37.5%, NPV 96.3%, LR+ 3.08, and LR- 0.198. In this study, the ACES score points that had significant values were cognitive symptoms (p 0.033) and speech problem (p 0.028). In focal seizures, APE2 has lower sensitivity, PPV, NPV and LR+ values but higher specificity and LR- compared to ACES. The APE2 score is less sensitive but quite specific with a high NPV. The ACES score is quite sensitive and specific with a high NPV. Both can be used for initial epilepsy screening, especially if there are symptoms of changes in mental status, viral prodromal symptoms, cognitive symptoms and speech problem before or at the onset of seizures. Further research is needed to assess other neural antibodies, examining neural antibodies in CSF and also including those whose seizure onset is less than 1 year, not limiting to drug-resistant epilepsy only."