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PENGARUH HIPERGLEMI TERHADAP PERAN SITOSKELETON (CYTOSKELETON) SEBAGAI JALUR TRANSDUKSI SIGNAL (SIGNAL TRANSDUCTION) Rudijanto, Achmad; Kalim, Handono
journal of internal medicine Vol. 7, No. 3 September 2006
Publisher : journal of internal medicine

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Abstract

Intracellular signal transduction occurs through cascades of reactions involving dozens of proteins that transmit signalsfrom the cell surface, through a crowded cellular environment filled with organelles and a filamentous cytoskeleton, to specifictarget. For most characterized signal transduction pathway, the initial signaling event and the end point are well known. In order tofully understand intracellular signal transduction, it is essential to know the intermediate signaling molecules and to understandhow information flows from one to the next. The cytoskeleton , an interconnected assembly of actin (microfilament), intermediatefilament and microtubule networks that extend throughout the entire cell, is involved in intracellular signal transduction.Individual proteins of the cytoskeleton might participate directly in signal transduction by linking two or more signaling proteinand might also provide a macromolecular scaffold, which spatially organizes components of a signal transduction cascade.Diabetes mellitus is an increasingly common disease. Absolute or relative deficiencies of insulin are common in this disease.Insulin has been suggested to play a key regulatory role in the functional organization of actin filaments. The microtubules are alsothe targets of insulin. A chronic insulin deficiency may could lead to impairment in the organization of the cytoskeleton. Thiscould entail a compromised or slower action of some activated enzymes in cells, affect to intracellular signal transduction.
PROTEINURIA SEVERITY IN LUPUS NEPHRITIS IS ASSOCIATED WITH ANTI-DSDNA LEVEL AND IMMUNE COMPLEX DEPOSIT LOCATION IN KIDNEY Engli, Katherina; Handono, Kusworini; Eko, Mudjiwijono Handaru; Susianti, Hani; Gunawan, Atma; Kalim, Handono
Journal of Tropical Life Science Vol 8, No 3 (2018)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.08.03.03

Abstract

Lupus nephritis (LN) is one of the manifestations of Systemic Lupus Erythematosus (SLE), with proteinuria being one of the clinical manifestations. The proteinuria pathogenesis is associated with anti-dsDNA antibody and the location of immune complex deposits within the kidney. This study aims to investigate the correlation of the severity of proteinuria with the location of immune complex deposits and the level of anti-dsDNA antibody in LN. Data were collected in cross-section. Fifty-three patients with LN in Saiful Anwar Hospital Malang, who underwent renal biopsy, were included. Hematoxylin-eosin staining and immunofluorescence analysis were used to assign subjects to different histopathological classes and determine the immune complex deposits. The spot urine samples were evaluated using the dipstick method for semi-quantitative proteinuria. The anti-dsDNA antibody levels were evaluated using the enzyme-linked immunosorbent assay (ELISA). Turbidity and enzymatic tests were conducted to elucidate urine protein and creatinine content, respectively. The level of proteinuria is significantly different among the different locations of immune complex based on the dipstick and protein/creatinine methods (p = 0.021 and p = 0.005, respectively). There was a significant correlation between anti-dsDNA antibody level and the severity of proteinuria (r = 0.326 based on dipstick and r = 0.28 based on protein/creatinine method). Thus, proteinuria in LN is determined by anti-dsDNA level and the location of immune complex deposits in the kidney.
PENGARUH CURCUMIN TERHADAP KADAR KOLESTEROL TOTAL, LDL-KOLESTEROL, JUMLAH F2 -ISOPROSTAN, DAN SEL BUSA (FOAM CELL) DINDING AORTA PADA TIKUS DENGAN DIET ATEROGENIK Fikriah, Ika; Kalim, Handono; Dradjat, Respati Suryanto
Jurnal Kedokteran Brawijaya Vol 21, No 2 (2005)
Publisher : Fakultas Kedokteran Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.jkb.2005.021.02.1

Abstract

ABSTRACT Death  caused  by  cardiovascular  and  cerebrovascular diseases  are  still  the  highest.  Atherosclerosis  due  to hypercholesterolemia is a predispositioning factor of both diseases. Curcumin has an antioxidant character that can inhibit lipid peroxidase to atherogenesis process. The aim of this study was to observe the effect of curcumin in decreasing total cholesterol level, LDL-cholesterol, the number of  F2-isoprostan and foam cell of aorta?s wall of white rats strain wistar after giving atherogenic diet for 10 weeks. There were 6 groups in this study (n=24): atherogenic diet group (group I as positive control), atherogenic diet group + curcumin 50 mg/kg b.w. per day (group II), atherogenic diet group + curcumin 100 mg/kg b.w. per day (group III), atherogenic diet group + curcumin 200 mg/kg b.w. per day (group IV), atherogenic diet group + curcumin 400 mg/kg b.w. per day (group V), normal diet group (group VI as negative control). After 10th, the level of total cholesterol and LDL-cholesterol were measured by spectrofotometri. Staining F2-isoprostan was done with Avidin Biotin Complex imunohystochemistry method, and staining foam cell with HE-oil Red O. The number of  F2-isoprostan and foam cells were counting semi quantitatively using  light microscope. The highest total cholesterol level was found in group I (275,15 ± 10,01; Mean ± SD), the highest LDL-cholesterol level was found in group I (158,15 ± 12,19). Statistically total cholesterol level and LDL-cholesterol level in group I were significantly higher (p ? 0,05) than other
KORELASI KADAR VITAMIN D, DENGAN TNF-α DAN MANIFESTASI KLINIS PADA PASIEN ARTRITIS REMATOID Ruliani, Hanik; Kalim, Handono; Suryana, BP Putra; Handono, Kusworini
Jurnal Kedokteran Brawijaya Vol 28, No 1 (2014)
Publisher : Fakultas Kedokteran Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.jkb.2014.028.01.7

Abstract

Artritis rematoid (AR) adalah penyakit autoimun yang ditandai dengan sinovitis erosif simetrik, diawali dengan  aktivasi sel T dependent antigen yang akan mencetuskan respon imun, terutama tipe Th1. Tumor necrosis factor (TNF-?) adalah sitokin sentral pada patogenesis AR.  Diketahui bahwa defisiensi vitamin D berkaitan dengan eksaserbasi respon imun Th1. Penelitian ini bertujuan untuk mengetahui korelasi kadar vitamin D dengan kadar TNF- ?, beratnya aktivitas penyakit pada pasien rematoid artritis. Penelitian cross sectional dilakukan pada pasien rawat jalan yang memenuhi kriteria inklusi sebanyak 24 pasien, kriteria diagnosis ditegakkan menurutkriteria ACR/EULAR 2010. Vitamin D dalam darah  dan TNF-?  diukur dengan metode ELISA, beratnya manifestasi klinis penyakit AR dinilai dengan score DAS28, VAS, dan skala fungsional. Sebesar 45,8% pasien mengalami defisiensi  vitamin D (36,13 ng/ml). Gangguan fungsional terbanyak adalah kelas I (66,6%). Terdapat korelasi yang bermakna antara vitamin D dengan usia pasien (p=0,005, r=-0,553), dengan lama sakit (p=0,009, r=-0,522), dengan DAS 28 (p=0,001, r=-0,615), banyaknya sendi yang sakit (p=<0,001, r=-0,733), dan sendi yang bengkak (p=0,045, r=-0,413), VAS pasien (p=0,006, r=-0,541) serta dengan kadar TNF  (p=0,048, r=-0,408) dan status fungsional pasien (p=0,039, r=-0,424). Hasil membuktikan bahwa kadar vitamin D dalam darah mempunyai hubungan dengan manifestasi klinis AR dan kadar TNFKata Kunci: Artritis rematoid, DAS 28, CRP, TNF VAS, vitamin D
PENINGKATAN KUALITAS SPERMATOZOA PADA PROSES PEMISAHAN SPERMATOZOA DENGAN SENTRIFUGASI GRADIEN DENSITAS PERCOLL MELALUI PEMBERIAN FOSFOLIPID Rumende, Rooije R.H.; Kalim, Handono; Widodo, M Aris; Djati, Moch Sasmito
Jurnal Kedokteran Brawijaya Vol 23, No 2 (2007)
Publisher : Fakultas Kedokteran Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.jkb.2007.023.02.3

Abstract

The separation of X and Y spermatozoa can be conducted by using Percoll Gradient Density Centrifugation(SGDP) method. It is, easy, valid, cheap and applicable method for developing made-insemination. Although it  has often been applied in sexing the spermatozoa, it was reported  that the method had often caused damages on the spermatozoa membranes and resulted in decreasing of the spermatozoa quality. The damages of spermatozoa after SGDP  process were specifically caused by (I) the loss of seminalplasma, (II) the increase of free radicals, and (III) the collision or friction among the spermatozoa. Among the three causal factors above, the third or the physical factor is claimed to be the most important one. It was assumed that the first and the second factors can be overcome if the third one is avoided. The spermatozoa membranes consist of lipids, protein, carbohydrate, and some substances at a low rate. Thegeneral objectives of this research was to identify the influence of the phospholipids PC (Phosphatidylcholin)to spermatozoa in order to avoid the damages of the spermatozoa in the process of SGDP.
Hubungan Kadar Vitamin D Dengan Jumlah Set T Regulator pada Pasien Lupus Eritematosus Sistemik Kalim, Handono; Handono, Kusworini; Hasanah, Dian
Research Journal of Life Science Vol 2, No 1 (2015)
Publisher : Lembaga Penelitian dan Pengabdian kepada Masyarakat, Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (593.976 KB) | DOI: 10.21776/ub.rjls.2015.002.01.5

Abstract

Latar Belakang. Lupus Eritematosus Sistemik (LES) merupakan penyakit autoimun yang semakin sering dijumpai dengan angka kematian tinggi. Etiopatogenesis penyakit ini belum begitu jelas, meskipun telah ditunjukkan adanya abnormalitas berbagai sel-sel imun termasuk hiper-reaktivitas sel T, sel B, sel dendrit; dan menurunnya fungsi sel T regulator (Treg). Vitamin D memiliki peran dalam pengaturan sistem imun. Penelitian pada ras Kaukasia menunjukkan bahwa kadar vitamin D yang rendah berkaitan dengan timbulnya penyakit autoimun termasuk LES. Peran vitamin D pada sistem imun pasien LES masih banyak kontroversi. Penelitian ini bertujuan untuk mengetahui hubungan kadar vitamin D dengan jumlah sel Treg.Metoda Penelitian. Penelitian ini adalah penelitian kasus-kontrol yang membandingkan jumlah sel Treg pada pasien LES dan kontrol sehat dengan melihat status vitamin D-nya. Kadar vitamin D pasien LES diukur dengan metoda ELISA, jumlah sel Treg (CD4+,CD25+,FoxP3+) ditentukan dengan metoda flowcytometri.Hasil. Kadar vitamin D pada pasien LES lebih rendah daripada kontrol sehat (p=0,000) dan didapatkan korelasi negatif antara status vitamin D dengan persentase sel Treg (koefisien korelasi -0,358 dan p=0,006). Hal ini mungkin merupakan umpan balik positif untuk menanggulangi hiperreaktifitas dari sel T dan sel B.Kesimpulan. Status vitamin D berkorelasi negatif dengan persentase sel Treg.
Validity and reliability fatigue severity scale in patients with Systemic Lupus Erythematosus (SLE) in Indonesia Rifa’i, A; Kalim, Handono; Handono, Kusworini; Wahono, Cesarius Singgih
Indonesian Journal of Rheumatology Vol 8, No 1 (2016)
Publisher : Indonesian Rheumatology Association

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Abstract

Background: Fatigue is one symptom of Systemic Lupus Erythematosus (SLE), which has an important effect on the quality of life. Fatigue Severity Scale (FSS)is one parameter fatigue symptom in SLE. The purpose of this study was to determine the validity and reliabilitybetween FSS with duration of ilness and disease activity of SLE patients in Indonesia.Methods: FSS performed on 40 patients with SLE. FSS original English version has been converted-translated into Indonesian version by a team of RheumatologyImmunology Medical Faculty of Brawijaya University. Reliability determined by Cronbach’s Alpha values (>0.6). Validity was determined by the value of Corrected Item-Total Correlation which each item was a valid question if below value of Cronbach’s Alpha.Results: The reliability value was determined by Cronbach’s Alpha values (>0.6) in which the SLE patients in this study had a Cronbach’s Alpha value of 0.946. Value of Corrected Item-Total Correlation overall under Cronbach’s Alpha value (range = 0.684-0.859) which indicates that each item was a valid question. There were correlation between the FSS Indonesian version with disease duration (p = 0.000) as well as the value of r = 0.581, with SLEDAI (p = 0.000) with a value of r = 0.833. Conclusion: FSS in Indonesian version has a good reliability and validity and can be used by clinicians andother researchers to assess the condition of fatigue in SLE patients in Indonesia.Keywords: validity, reliability, fatigue, fatigue severity scale, systemic lupus erythematosus
Validation of Modified COPCORD Questionnaire Indonesian Version as Screening Tool for Joint Pain and Musculoskeletal Diseases Anshory, Muhammad; Wahono, Cesarius Singgih; Kalim, Handono; Al Rasyid, Harun
Indonesian Journal of Rheumatology Vol 10, No 1 (2018)
Publisher : Indonesian Rheumatology Association

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Abstract

Background: WHO-ILAR COPCORD Program is a program that aimed to obtain data on joints pain and musculoskeletal diseases in developing countries, one aspect which has not been studied is the ability of COPCORD questionnaire as a screening tool which standardized for  screening  joint pain and musculoskeletal diseases. Objective of this study is to assess the validity of modified COPCORD questionnaire Indonesian version in screening joint pain and musculoskeletal disease compared to examination by rheumatologists.Methods: The initial phase of the research is determining essential points, translation to Indonesian, and back translation. The second stage is testing questionnaires in communities which 100 respondents involved. Dependent variable is the diagnosis of rheumatic diseases and independent variables are pain in less and more than 7 days, high degree pain in less and more than 7 days, history of NSAIDs/Steroids/DMARDs use, and disabilities. Validation test was assessed by calculating the sensitivity, specificity, PPV, NPV, LR+, and ROC curve. Bivariate analysis using Chi Square analysis, and multivariate analysis using logistic regression.Results: The sensitivity test results is best obtained on the question history of NSAIDs/steroids/DMARDs use (100%)  and specificity is best obtained on the question about disability (98%). ROC curve analysis which the results >85% obtained on the question of pain >7 days (90%), high degree pain >7 days (93%), and history of NSAIDs/steroids/DMARDs use (92%).  LR+ to diagnose rheumatic diseases found in all questions. Chi square analysis showed that all questions were significant with p <0.05 and odds ratio (OR) obtained most on high degree pain more than 7 days (OR: 180.167; 95% CI: 38.196-849.834).Conclusion: The modified COPCORD questionnaire Indonesian version has been adapted and can be a good tool in the screening of joint pain and musculoskeletal diseases compared to examination by rheumatologists. Keyword: Validation, Questionnaire, COPCORD
The Use of Tocilizumab in Combination with Methotrexate in Indonesian Rheumatoid Arthritis Patients (PICTURE INA Study) Setyohadi, Bambang; Isbagio, Harry; Wachjudi, Rachmat Gunadi; Soeroso, Joewono; Kalim, Handono; Achadiono, Deddy Nur Wachid
Indonesian Journal of Rheumatology Vol 10, No 1 (2018)
Publisher : Indonesian Rheumatology Association

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Abstract

Background Aim of this research is to assess the efficacy and safety of tocilizumab (TCZ) in combination with methotrexate (MTX) in Indonesian patients with moderate to severe active rheumatoid arthritis (RA) who have an inadequate response to non-biologic DMARDs.Methods This was a interventional, prospective, single arm, multicenter, study in  Indonesian male or female patients aged ≥ 18 years old, with a diagnosis of RA for > 6 months based on ACR 1987 revised criteria with moderate to severe disease activity (DAS28 score > 3.2) after ≥ 12 weeks of non-biologic DMARDs treatment. The treatment consisted of tocilizumab, 8 mg/kg, intravenous (IV), every 4 weeks for a total of 6 infusion in combination with oral MTX (10−25 mg) every week. Efficacy was assessed based on the percentage of patients achieving low disease activity state (DAS28 < 3.2), percentage of patients achieving reduction > 1.2 point of DAS28, percentage of patients achieving remission (DAS28 < 2.6), and percentage of patients with ACR20, ACR50, and ACR70 responses. Descriptive statistics will be used for presentation of results.Results 100% patients reached low disease activity (DAS28 ≤ 3.2) at last study visit (week 24) and clinically significant improvement (reduction at least 1.2 units) at every visit in DAS28, both for ITT or PP patients. Remission (DAS28 < 2.6) was observed in 82.1% (ITT patients) and 93.1 % (PP patients) on last study visit. ACR20, ACR50, and ACR70 were achieved in 20%, 34%, and 34% (ITT patients), and 7%, 24%, and 62% (PP patients) on week 24. There were 3 out of 39 patients (7.69%) with adverse events (AE) and serious adverse events (SAE) that resulted in discontinuation of TCZ treatment, consisting of 1 patient with SAE of sepsis ec acquired community pneumonia, 1 patient with SAE of pneumonia tuberculosis, and 1 patient with AE of candidiasis. Most common adverse events were hepatic dysfunction (30.7%), hypercholesterolemia (23.1%), followed by arthralgia (20.5%) Twelve percent of patients needed dose modification due to elevated liver enzyme (elevated ALT/SGPT level).Conclusion Tocilizumab seems to be efficacious and likely to have good safety profile in non- biologic DMARD nonresponsive RA patients of PICTURE INA study.   Keywords: Rheumatoid Arthritis, Tocilizumab, DMARD, DAS28
Correlation between anti-cyclic citrullinated peptide antibodies and the severity of clinical manifestation, laboratory manifestation, and radiological joint destruction in rheumatoid arthritis patients Suwito, Mat; Handono, Kusworini; Suryana, Bagus Putu Putra; Kalim, Handono; Wahono, Cesarius Singgih
Indonesian Journal of Rheumatology Vol 2, No 1 (2010)
Publisher : Indonesian Rheumatology Association

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Abstract

Background. The second generation anti-cyclic citrullinated peptide test (CCP2) displays sensitivity comparable to that of rheumatoid factor (RF) (approximately 80%) but with superior specificity (98%) . Several observations have indicated that early rheumatoid arthritis (RA) patients with positive anti-CCP may develop a more erosive disease than those without anti-CCP.Objective. The purpose of this cross-sectional study was to investigate the correlation between anti-CCP antibodies and clinical and laboratory parameters and radiological joint destruction in RA patients.Methods. We studied 31 patients with RA fulfilling the 1987 revised criteria of American College of Rheumatology in Rheumatology Clinic of Saiful Anwar General Hospital, Malang, Indonesia. Clinical parameters were collected such as age, sex, visual analog scale,disease duration and diseases activity score (DAS28-3(CRP)). Laboratory parameters were WBC, hemoglobin, platelet count, erythrocyte sedimentation rate, and Creactive protein. Analyzed autoantibody profiles were RF and anti-CCP (ELISA methode). Radiological jointdestruction was evaluated from bilateral postero-anterior manus x ray (Sharp score).Results. Anti-CCP antibodies were detected in 48.4% of RA patients with mean antibody concentration was 291.24±143.67 (range 16-523.8) units. Anti CCP level was significantly correlated with duration of RA (month) (p=0.04, r=0.371), RF level (p=0.002, r=0.542) andSharp score (p=0.048, r=0.358), but was not significantly correlated with other clinical and laboratory parameters.Conclusion. Anti-CCP level was correlated with duration of disease, RF, and Sharp score.