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"Background: The determination of branched chain amino acids (BCAA) to tyrosine ratio (BTR) was available in making differentiation of chronic hepatitis from liver cirrhosis, because there was a strong association between BTR and staging (fibrosis) scores. Branched chain ammo acids to tvrosine ratio have a correlation with Fischer ratio and the examination is easier because it can be done by enzymatic assay.Materials and Methods: To evaluate the correlation between BTR and Child-Pugh score, we examined the amino gram of 52 liver cirrhosis patients consisted of 26 Child-Pugh A, 19 Child-Pugh B, and 7 Child-Pugh C. The examination of amino gram was done by High Pressure Liquid Chromatograph (HPLC) analyzer. Branched chain amino acids to tyrosine ratio were compared to Child-Pugh score, albumin, ammonia level, number connection test to Fischer ratio.Results: Significant differences in BTR among Child-Pugh A, B, C were observed (Child-Pugh A 7.75 ± 1.2; Child Pugh B 6.0 ± 1.23 and Child Pugh C 4.38 + 3.14 (p = 0.000)). Branched chain amino acids to tyrosine ratio had a weak correlation with albumin fr - 0.292; p = 0.036), ammonia level (r = 0.376; p = 0.006) and strong correlation with Fischer ratio (r = 0.818; p = 0.000). There was no significant correlation between BTR and number connection test.Conclusion: These results showed that the determination of the molar ratio of branched chain amino acids to tyrosine well reflected the severity of liver cirrhosis and it can be used as a substitute of Fischer ratio."

"Penelitian ini bertujuan untuk menganalisis peran mutasi gen FLT3 dalam resistensi terapi induksi D3A7 pada pasien LMA, melalui pengamatan perubahan struktur protein reseptor FLT3, aktivitas jalur persinyalan downstream FLT3 yaitu PI3K/AKT, menggunakan persentasi jumlah sel yang berapoptosis dan proliferasi sebagai indikator dalam mekanisme multidrug resistance terhadap terapi induksi D3A7. Selain itu dilakukan juga analasis peran sub populasi sel punca leukemia CD34+CD38-CD123+ dan marka ALDH dalam resistensi terapi Induksi D3A7, untuk mengetahui hubungannya denagn resistensi terapi induksi D3A7. Metode Deteksi mutasi gen FLT3 dilakukan dengan PCR-sekuensing dari sampel darah sumsum tulang pasien LMA de novo yang telah selesai diberikan terapi induksi D3A7. Sikuens gen yang termutasi kemudian dianalisis menggunakan studi in silico untuk menilai dampak dari mutasi gen terhadap perubahan struktur dan aktivitas pengikatan protein terhadap regimen sitarabin. Analisis aktivitas fosforilasi protein PI3K dan AKT dilakukan dengan metode sandwich ELISA. Penghitungan persentasi jumlah sel yang mengalami apoptosis dan proliferasi, serta deteksi sel punca leukemia dengan penanda CD34+, CD38-, CD123+, dan ALDH menggunakan Flowcitometry. Hasil Ditemukan mutasi baru Ins_572G573 (Insersi-G) pada domain juxtamembran dari protein reseptor FLT3 dengan frekuensi sebesar 30% dari total 20 pasien LMA yang direkrut, sementara frekuensi mutasi FLT3-ITD yang diperoleh sebesar 20%. Kelompok pasien dengan mutasi gen FLT3 mengalami peningkatan fosforilasi protein PI3K dan AKT yang bermakna secara statistik, mengalami peningkatan rerata persentasi jumlah proliferasi sel dan penurunan rerata jumlah apoptosis sel dibandingkan kelompok tanpa mutasi. Kelompok pasien dengan outcome terapi resistensi juga mengalami peningkatan fosforilasi protein PI3K dan AKT, penurunan rerata jumlah sel yang mengalami apoptosis dan peningkatan rerata jumlah sel yang berproliferasi. Penanda sel punca leukemia CD34+, CD38-, CD123+, dan ALDH memiliki hubungan tidak bermakna dengan resistensi terapi induksi D3A7. Kesimpulan Penelitian ini menunjukkan bahwa mutasi gen FLT3 tidak berhubungan lansung pada resistensi terapi D3A7. Namun perubahan struktur protein akibat mutasi berperan penting dalam mekanisme resistensi melalui aktivasi jalur pro-proliferasi dan anti papoptosis dari persinyalan PI3K/AKT. Salain itu, penanda sel punca leukemia tidak berhubungan dengan resistensi terapi induksi D3A7.......Introduction This study aims to analyze the role of FLT3 gene mutations in the resistance of AML therapy induction with D3A7 in patients, through observing changes in FLT3 receptor protein structure, the activity of downstream FLT3 signaling pathways such as PI3K/AKT, and using the percentage of apoptotic and proliferative cells as indicators in the mechanism of multidrug resistance against D3A7 induction therapy. Additionally, the study also analyzes the role of leukemia stem cell subpopulations CD34+CD38-CD123+ and ALDH markers in resistance to D3A7 induction therapy, to understand their relationship with resistance to D3A7 induction therapy. Method Detection of FLT3 gene mutations was performed by PCR-sequencing from bone marrow blood samples of de novo AML patients who had completed D3A7 induction therapy. Sequences of the mutated genes were then analyzed using in silico studies to assess the impact of gene mutations on structural changes and protein binding activity with cytarabine regimens. Analysis of PI3K and AKT protein phosphorylation activity was conducted using sandwich ELISA. Calculation of the percentage of cells undergoing apoptosis and proliferation, as well as detection of leukemia stem cells marked by CD34+, CD38-, CD123+, and ALDH, was performed using Flow cytometry. Results A novel mutation, Ins_572G573 (Insertion-G), was found in the juxtamembrane domain of the FLT3 receptor protein with a frequency of 30% among a total of 20 recruited AML patients. Meanwhile, FLT3-ITD mutation frequency was obtained at 20%. Patients with FLT3 gene mutations showed statistically significant increases in PI3K and AKT protein phosphorylation, as well as higher average percentages of proliferating cells and lower average percentages of apoptotic cells compared to the non-mutation group. Patients in the therapy-resistant outcome group also exhibited increased PI3K and AKT protein phosphorylation, decreased average percentages of apoptotic cells, and increased average percentages of proliferating cells. However, leukemia stem cell markers CD34+, CD38-, CD123+, and ALDH did not show statistically significant associations with resistance to D3A7 induction therapy. Conclusion This study indicates that FLT3 gene mutations do not directly correlate with resistance to D3A7 therapy. However, structural changes in proteins due to mutations play a crucial role in resistance mechanisms through the activation of pro-proliferation and anti-apoptosis pathways via PI3K/AKT signaling. Additionally, leukemia stem cell markers are not associated with resistance to D3A7 induction therapy."

"Background: The determination of branched chain amino acids (BCAA) to tyrosine ratio (BTR) was available in making differentiation of chronic hepatitis from liver cirrhosis, because there was a strong association between BTR and staging (fibrosis) scores. Branched chain ammo acids to tyrosine ratio have a correlation with Fischer ratio and the examination is easier because it can be done by enzymatic assay.Materials and Methods: To evaluate the correlation between BTR and Child-Pugh score, we examined the amino gram of 52 liver cirrhosis patients consisted of 26 Child-Pugh A, 19 Child-Pugh B, and 7 Child-Pugh C. The examination of amino gram was done by High Pressure Liquid Chromatograph (HPLC) analyzer. Branched chain amino acids to tyrosine ratio were compared to Child-Pugh score, albumin, ammonia level, number connection test to Fischer ratio.Results: Significant differences in BTR among Child-Pugh A, B, C were observed (Child-Pugh A 7.75 ± 1.2; Child Pugh B 6.0 ± 1.23 and Child Pugh C 4.38 + 3.14 (p = 0.000)). Branched chain amino acids to tyrosine ratio had a weak correlation with albumin fr - 0.292; p = 0.036), ammonia level (r = 0.376; p = 0.006) and strong correlation with Fischer ratio (r = 0.818; p = 0.000). There was no significant correlation between BTR and number connection test.Conclusion: These results showed that the determination of the molar ratio of branched chain amino acids to tyrosine well reflected the severity of liver cirrhosis and it can be used as a substitute of Fischer ratio."

"ABSTRAKMola hidatidosa merupakan penyakit trofoblas yang disertai peningkatan kadar Human Chorionic Gonadotropin (= HCG). Telah dilaporkan terjadinya gejala hipertiroidisme pada panderita mola yang ada kemungkinan berlanjut dengan timbulnya penyulit krisis tiroid yang dapat berakibat fatal. Hiperfungsi tiroid tersebut disebabkan pengaruh keaktifan tirotropik dari HCG. Penelitian ini bertujuan untuk memantau kadar hormon tiroid pada penderita mola hidatidosa. Dari bulan Maret sampai dengan Agustus 1986 telah diperiksa serum dari 12 penderita MR. Pemeriksaan dilakukan secara serial: sebelum pengeluaran jaringan mola, lalu dilanjutkan pada hari ke 3 - 5, 1 bulan dan 2 bulan sesudahnya. Dilakukan penetapan kadar hormon tiroksin (= T4) dan ambilan tiroksin (= Ambilan T4) dengan cara "Enzyme Immuno Assay" (=EIA) menggunakan kit ENDAB Irmruno Assay, kemudian nilai Indeks tiroksin babas (= ITB) dihitung. Diperiksa pula kadar "Thyroid Stimulating Hormone" (=TSH) dengan cara Radio Immuna Assay (=RIA) dan kadar hCG urin dengan test aglutinasi. Sebelum dilakukan pengeluaran jaringan mola ke 12 kasus semuanya menunjukkan tanda tanda hipertiroidisme secara laboratoris (Ti, ambilan T4, ITB) dengan atau tanpa disertai gejala klinia. Setelah pengeluaran jaringan mola kelainan ini akan menurun dan mencapai kadar normal pada kurang lebih 1 bulan sesudahnya. Kadar TSH makin meningkat tetapi masih dalam batas batas normal. Keadaan ini seiring dengan penurunan kadar hCG urin. Hasil-hasil tersebut sesuai dengan yang didapatkan oleh peneliti peneliti terdahulu. Disarankan untuk memasukkan pemeriksaan kadar hormon tiroid pada protokol panatalaksanaan penderita mola hidatidosa untuk mempertimbangkan pengobatan terhadap kelainan barman ini dan menghindari penyulit yang mungkin terjadi. "

"Latar belakang. Spermatozoa pada dasarnya merupakan sel yang inaktif secara transkripsi maupun translasi, sehingga dibutuhkan serangkaian perubahan pasca translasi untuk meregulasi fungsi sel tersebut sehingga mampu membuahi sel telur. Salah satu perubahan tersebut adalah proses kapasitasi yang ditandai dengan meningkatnya fosforilasi protein-protein pada residu tirosin. Testosteron telah diketahui memiliki efek non genomik pada sel, dan diketahui pula bahwa pada spermatozoa yang telah diejakulasikan terdapat reseptor androgen yang terlokalisasi di bagian ekor spermatozoa. Namun, pengaruh testosteron terhadap peningkatan kapasitasi spermatozoa yang telah diejakulasikan belum banyak diketahui. Oleh karena itu, penelitian ini dilakukan untuk mengetahui efek penambahan testosteron terhadap parameter-parameter yang berkaitan dengan proses kapasitasi spermatozoa yang dilakukan secara In vitro. Metode. Sampel semen didapatkan dari 15 donor pria normozoospermia, yang di inkubasi dengan testosteron dengan delapan kosentrasi berbeda, yaitu 0, 25 50, 100, 250, 500, 750 dan 1000 ng/mL selama 60 menit dan 120 menit. Terdapat 5 parameter yang diukur yakni viabilitas dan motilitas dengan menghitung persentase dari 100 sel; integritas membran dengan uji Hypo-osmotic swelling; fosforilasi protein residu tirosin dengan teknik western blot; dan lokalisasinya dideteksi dengan teknik imunositokimia. Hasil kemudian dianalisis secara statistik menggunakan program SPSS. Hasil. Pengukuran efek testosteron terhadap lima parameter yang diukur memiliki pola yang sama. Viabilitas, motilitas, integritas membran dan fosforilasi protein residu tirosin memiliki kecenderungan meningkat seiring dengan peningkatan konsentrasi, optimum pada konsentrasi 100-250 ng/mL, namun mengalami kecenderungan penurunan pada inkubasi 500-1000 ng/mL. Peningkatan persentase pada viabilitas pada kelompok kontrol sebesar 49% dan meningkat menjadi 57% pada konsentrasi 250 ng/mL; persentase motilitas meningkat dari 49% menjadi 56%; persentase sperma yang baik integritas membrannya meningkat dari 51% menjadi 55%; dan spermatozoa yang terfosforilasi protein residu tirosinnya meningkat dari 24% menjadi 53%. Akan tetapi, kecenderungan peningkatan tersebut secara statistik tidak berpengaruh secara signifikan (p>0,05). Kesimpulan. Testosteron cenderung meningkatkan Viabilitas, Motilitas, Integritas Membran, dan fosforilasi residu tirosin pada protein spermatozoa.

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Background. Spermatozoa depends on post translational modifications to regulate its function. They have to undergo a series of processes called capacitation that make it capable of fertilizing the oocyte.. Phosphorylation of tyrosine residues is one of the post translational modifications which constitute characteristic of capacitation. Testosterone has been known to have non-genomic effects on cells, However, the effect of testosterone on the sperm capacitation has not been known. Therefore, this study is aimed to analyze the effect of the addition of testosterone on sperm capacitation in vitro.

Method. Semen samples are obtained from 15 male normozoospermic donors, incubated with testosterone with eight different concentrations; 0 ng/mL, 25 ng/mL, 50 ng/mL, 100 ng/mL, 250 ng/mL, 500 ng/mL, 750 ng/mL and 1000 ng/mL in 60 minutes and 120 minutes. There are five parameters measured include the viability and motility by calculate the percentage of the 100 cells; membrane integrity with Hypo-osmotic swelling test; Phosphorylation of tyrosine residues of proteins by western blot technique; and its localization detected by immunocytochemistry technique. The results were analyzed statistically using SPSS.

Results. Measurement of testosterone effects of five measured parameters has the same pattern. Viability, motility, membrane integrity and phosphorylation of tyrosine residues of protein have tendency to increase in higher concentration. The optimum concentration is 100-250 ng/mL, whereas the tendency to decrease at the concentration 500-1000 ng/mL. The percentage of viability in the control group is 49% and increased to 57% at 250 ng/mL concentration; the percentage of motility increased from 49% to 56%; the percentage of sperm membrane integrity increased from 51% to 55%; and the percentage of phosphorylation of tyrosine residues increased from 24% to 53%. However, the increasing trend is statistically not significant (p>0.05).

Conclusion. Testosterone tends to increase the viability, motility, membrane integrity, and also phosphorylation of tyrosine residues of proteins in sperm cells."

"LATAR BELAKANG : Infertilitas pada laki-laki sering dikaitkan dengan konsentrasi sel spermatozoa yang rendah, terganggunya motilitas dan juga morfologi sel spermatozoa normal yang rendah. Stres oksidatif merupakan suatu kondisi yang mencerminkan ketidakseimbangan antara keberadaan Reactive Oxygen Species (ROS). Bertujuan untuk menganalisis aktivasi fosforilasi protein tirosin setelah diberikan penambahan H2O2 pada sel spermatozoa. BAHAN DAN CARA KERJA : Sampel sel spermatozoa ditambahkan H2O2 dengan berbagai konsentrasi, 0 (kontrol), 50M, 100­M, 150­M, 200M, 250M. Kemudian dilakukan pemeriksaan motilitas dengan Makler, integritas membran dengan metode HOS, pemeriksaan kemampuan penetrasi lendir serviks dengan capillary tube, dan deteksi aktivasi fosforilasi protein tirosin dilakukan dengan metode western blot. HASIL : efek penambahan H2O2 menurunkan rerata motilitas sel spermatozoa (p<0,05). Menurunkan integritas membran, menurunkan kemampuan sel spermatozoa untuk penetrasi lendir serviks. Analisis western blot menujukkan terjadinya penurunan fosforilasi protein tirosin pada setiap kelompok perlakuan, penuruan yang terjadi signifikan terdapat pada konsentrasi 150M dan 200M (p<0,05). KESIMPULAN : Konsentrasi tinggi H2O2 mempunyai pengaruh yang besar dalam menurunkan motilitas, merusak integritas membran, menurunkan kemampuan penetrasi lendir serviks dan terhambatnya aktivasi fosforilasi protein tirosin pada sel spermatozoa. ......BACKGROUND : Infertility in men is often associated with low spermatozoa cell concentrations, impaired motility and also low normal spermatozoa cell morphology. Oxidative stress is a condition that reflects an imbalance between the existence of Reactive Oxygen Species (ROS). Aim to analyze the activation of tyrosine protein phosphorylation after adding H2O2 to spermatozoa cells. METHODS : Spermatozoa cell samples were added H2O2 with various concentrations, 0(controls),50M,100M,150M,200M,250M. Then the motility test with Makler, membrane integrity with the HOS method, examination of the ability to penetrate the cervical mucus with the capillary tube, and detection of activation of tyrosine protein phosphorylation was carried out by western blot method. RESULTS : the effect of adding H2O2 decreased the average motility of spermatozoa cells (p <0.05). Reduces membrane integrity, decreases the ability of spermatozoa cells to penetrate cervical mucus. Western blot analysis showed a decrease in tyrosine protein phosphorylation in each treatment group, a significant reduction in the concentration of 150M and 200M (p <0.05). CONCLUSION : High concentrations of H2O2 have a large influence in reducing motility, damaging membrane integrity, decreasing the ability to penetrate cervical mucus and inhibiting activation of phosphorylation of tyrosine proteins in spermatozoa cells. "

"Latar Belakang: Jumlah kasus KPKBSK diperkirakan 85% dari seluruh kasus kanker paru dan 40% diantaranya adalah jenis adenokarsinoma. Sebanyak 10%-30% pasien adenokarsinoma mengalami mutasi EGFR dan mendapatkan terapi EGFR-TKI. Mayoritas pasien KPKBSK memiliki respons dan toleransi baik terhadap terapi EGFR- TKI tetapi sebagian kecil pasien mengalami penyakit paru interstisial akibat EGFR- TKI. Penelitian ini bertujuan untuk mengetahui proporsi gambaran penyakit paru interstisial pada pasien KPKBSK dengan terapi EGFR-TKI di RSUP Persahabatan.Metode: Penelitian ini merupakan penelitian observasional analitik dengan pendeketan kohort retrospektif yang dilakukan bulan Januari 2021 hingga Juni 2022. Subjek penelitian adalah pasien KPKBSK yang mendapatkan terapi EGFR-TKI. Subjek penelitian dipilih sesuai kriteria inklusi dan eksklusi. Pengambilan data melalu data sekunder berupa rekam medis dan hasil CT scan toraks pasien yang kontrol di poliklinik onkologi RSUP Persahabatan.Hasil: Pada penelitian ini diperoleh 73 subjek penelitian, pasien KPKBSK dengan mutasi EGFR yang mendapatkan terapi EGFR-TKI di RSUP Persahabatan. Sebanyak 12 dari 73 subjek penelitian mengalami gambaran ILD yang dievaluasi berdasarkan CT scan toraks RECIST I dan II dengan karakteristik jenis kelamin laki-laki (22,2%), kelompok usia 40-59 tahun (19,4%), perokok (24,1%), indeks brinkman berat (42,9%) dan mendapatkan terapi afatinib (26,1%). Proporsi gambaran ILD pada pasien KBPKBSK dengan terapi EGFR-TKI adalah opasitas retikular (58,3%), parenchymal band (33,3%), ground-glass opacities (25%), traction bronchiectasis (25%) dan crazy paving pattern (8,3%). Hasil analisis bivariat dan multivariat menunjukkan tidak terdapat perbedaan antara faktor-faktor seperti jenis kelamin, usia, jenis EGFR-TKI, riwayat merokok, indeks brinkman, riwayat penyakit paru dan tampilan status terhadap gambaran ILD.Kesimpulan: Gambaran ILD pada pasien KPKBSK dengan terapi EGFR-TKI meliputi opasitas retikular, parenchymal band, ground-glass opacities, traction bronchiectasis dan crazy paving pattern. Tidak terdapat perbedaan bermakna secara statistik antara faktor-faktor yang memengaruhi terhadap gambaran ILD.......Background: The number of cases of NSCLC is estimated around 85% of all lung cancer cases and 40% among them are adenocarcinoma. Approximately 10%-30% of adenocarcinoma patients have EGFR mutations and receive EGFR-TKI therapy. The majority of NSCLC patients have a good response and tolerance to EGFR-TKI therapy, but a small group of patients experience EGFR-TKI induced interstitial lung disease. This study aims to determine the proportion of features of interstitial lung disease ini NSCLC patients treated with EGFR-TKI at Persahabatan Hospital.Methods: This study was an analytic observational with a retrospective cohort approach that was conducted from January 2021 until June 2022. The subject were NSCLC patients who received EGFR-TKI treatment. The inclusion and exclusion criteria were used to determine which subjects will be included in the study. Data collection through secondary data from medical record and chest CT scan results of patients controlled at oncology polyclinic at Persahabatan Hospital.Result : In this study, there were 73 subjects of NSCLC with EGFR mutations and received EGFR-TKI therapy at Persahabatan Hospital. There were 12 out of 73 subjects had ILD features which were evaluated based on RECIST I and II chest CT scan with predominant of male (22.2%), age group 40-59 years old (19.4%), smokers (24.1%), severe Brinkman index (42.9%) and received afatinib (26.1%). The proportion of ILD features in NSCLC patients with EGFR-TKI therapy are reticular opacities (58.3%), parenchymal bands (33.3%), ground-glass opacities (25%), traction bronchiectasis (25%) and crazy paving pattern (8.3%). The results of bivariate and multivariate analyzes showed that there was no differences between factors such as sex, age, type of GEFR-TKI, smoking history, Brinkman index, history of lung disease and performance status with features of ILD.Conclusion: Features of ILD in NSCLC patients with EGFR-TKI therapy include reticular opacities, parenchymal bands, ground-glass opacities, traction bronchiectasis and crazy paving pattern. There is no statistically significa"