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"Background: Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, both proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-β. TLR2 gene polymorphism is strongly determined by ethnicity and geography. Therefore it is necessary to uncovered the existence and association between Arg753Gln and Arg677Trp TLR2 gene polymorphism with TB susceptibility and its underlying mechanisms in Indonesian population in Bandung West Java. Methods: analytical observational study with cross-sectional design was conducted in Hasan Sadikin General Hospital Bandung from April 2011 to May 2012. Study population consisted of active pulmonary TB patient with positive AFB smear and Latent TB to ascertain previous MTb exposure. Polymorphism of gen Arg753Gln and Arg677Trp gene was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Plasma levels of IFN-γ, TNF-α, IL-10 and IL-12 were also compared between active and latent TB group. Results: heterozygote Arg753Gln TLR2 gene polymorphism was found in 9 of 86 pulmonary TB subjects (10.5%) but none in the latent TB group. The Arg677Trp polymorphism was not found in both groups. The odds ratio for Arg753Gln existence was 28.07 (p=0.022). No differences in the levels of IFN-γ, TNF-α, IL-10 and IL-12 between active pulmonary TB and latent TB subjects with and without Arg753Gln TLR2 gene polymorphism. Conlusion: Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not. The Increased risk is not mediated by the difference in IFN-γ, TNF-α, IL-10 and IL-12 serum levels."

"ABSTRAKBackground: diagnostic of pulmonary TB in HIV patients is a problem due to non specific clinical features, or radiological appearance. HIV patients with CD4≤200 cells/mL infected with M. tuberculosis have less capacity in containing M. tuberculosis, developing granulomas, casseous necrosis, or cavities. This condition is caused by weakend inflammatory which later reduced sputum production and may cause false negative result. This study aimed to assess differences in the positivity level of acid fast bacilli (AFB) and cultures of M. tuberculosis from non-bronchoscopic sputum (spontaneous and induced sputum) compared to bronchoscopic sputum (bronchoalveolar lavage) in HIV positive patients suspected pulmonary tuberculosis with CD4<200 cells/μL.Methods: this cross sectional study was conducted in adult HIV patients treated in Hasan Sadikin Hospital with CD4≤200 cells/μL suspected with pulmonary tuberculosis by using paired comparative analytic test. All patients expelled sputum spontaneously or with sputum induction on the first day. On the next day, bronchoalveolar lavage (BAL) was performed. The two samples obtained from two methods were examined by AFB examination with staining Ziehl Neelsen (ZN) and cultured of M. tuberculosis on solid media Ogawa on all patients. Positivity, sensitivity and increased sensitivity of AFB and culture of M. tuberculosis in the non bronchoscopic and bronchoscopic groups were compared.Results: there were differences in the positivity level of AFB with ZN staining between non-bronchoscopic and bronchoscopic groups which were 7/40 (17.5%) vs 20/40 (50.0%) (p<0.001). The differences between the cultures of non-bronchoscopic and bronchoscopic groups were 16/40 (40.0%) vs 23/40 (57.5%) (p=0.039). Bronchoscopic sputum increased the positivity level of the ZN AFB examination by 32.5% (from 17.5% to 50.0%) as well as on culture examination by 17.5% (from 40.0% to 57.5%).Conclusion: Bronchoalveolar lavage can improve the positivity level of smears and cultures in patients suspected of pulmonary TB in HIV patients with CD4<200 cells/μL."

"Background: Diabetic kidney disease (DKD), as a common cause of end-stage renal disease (ESRD), is a chronic complication of diabetes mellitus (DM). It has been established that vitamin D deficiency is one of DKD risk factors, which may be related to vitamin D receptor (VDR) polymorphisms. This study aimed to analyze the association between VDR polymorphisms and DKD in Indonesian population, also risk factors that influence it. Methods: a cross-sectional study was conducted in Type 2 DM patients who visited internal medicine outpatient clinic at Dr. Cipto Mangunkusumo Hospital, Jakarta, from November 2014 until March 2015. Data collection includes characteristics of subjects and laboratory examination, including BsmI polymorphisms in the vitamin D receptor gene. Patients with acute and severe disease were excluded from the study. Bivariate and multivariate analyses were done. Results: of 93 DM subjects, 42 (45.2%) subjects were without DKD and 51 (54.8%) subjects had DKD. Most of the subjects had the Bb genotype (89.2%), with no subject having the BB genotype. The proportions of the B and b alleles were 44.6% and 55.4%, respectively. There is no association between BsmI polymorphisms in the vitamin D receptor gene and DKD (OR = 1.243; CI 95% 0.334-4.621; p value = 0.751). Conclusion: the profile of BsmI polymorphisms in the vitamin D receptor gene in the Indonesian population were genotypes Bb (89.2%) and bb (10.8%). There was no association between BsmI polymorphisms in the vitamin D receptor gene and DKD. Duration of DM more than five years influenced the association between those variables."

"ABSTRAKBackground: diabetic nephropathy (DN) is the leading cause of blood dialysis worldwide and a major etiology of End-Stage Renal Disease cases in Indonesia. Previous studies showed a relevant link between A1166C polymorphism of Angiotensin II Type-1 Receptor (AT1R) gene and glomerular hyper-filtration as a part of pathogenesis of DN. The aim of this study was to elaborate the association between A1166C AT1R polymorphism and susceptibility of individual with type-2 diabetes to DN in Malay Indonesian population. Methods: a case-control study of 120 consecutive patients with type-2 diabetes mellitus (40 patients in each groups for macro-albuminuria, micro-albuminuria, and normo-albuminuria) was conducted for A1166C AT1R gene polymorphism. The A1166C polymorphism of the AT1R gene was determined based on PCR/RFLP. Results: the mutant C allele was found in 5%, 13.75%, and 12.5% in normo-, micro-, and macro-albuminuria patients respectively. The heterozygote AC genotype was found significantly higher in micro-albuminuria, compared to normo-albuminuria group. Heterozygote AC genotype (OR 3.2 [1.01-10.08], p=0.03) and C allele (OR 2.8[0.95-8.67], p=0.038) were significantly higher in DN, indicating A1166C AT1R gene polymorphism as a risk factor for DN in Malay Indonesian population with type-2 diabetes. Conclusion: there was positive association between A1166C AT1R polymorphism and susceptibility of type-2 diabetics to DN in Malay Indonesian Population. It also indicated that the A1166C AT1R polymorphism could play a role in early pathogenesis of DN."

"Infertilitas pria paling banyak disebabkan oleh gangguan proses spermatogenesis. Androgen merupakan hormon yang sangat penting pada proses spermatogenesis. Aksi biologis hormon androgen terjadi melalui interaksi dengan reseptor androgen (RA) yang merupakan protein regulator transkripsi di dalam nukleus. Ekson 1 gen RA mengandung pengulangan trinukleotida CAG yang bersifat polimorfik. Polimorfisme pengulangan trinukleotida CAG ini diduga mempengaruhi aktivitas reseptor androgen. Penelitian meliputi isolasi DNA dari darah tepi dan amplifikasi fragmen pengulangan trinukleotida CAG gen RA dengan teknik PCR. Penentuan panjang pengulangan CAG gen RA dilakukan dengan elektroforesis pada gel poliakrilamid 6% yang mengandung zat pendenaturasi. Dari penelitian ini didapatkan perbedaan jumlah pengulangan CAG gen reseptor androgen antara pria oligozoospermia/azoospermia (24,3 ± 3,4) dan pria normozoospermia (22,7 ± 2,7). Berdasarkan uji t untuk sampel tidak berpasangan, perbedaan jumlah pengulangan CAG pada gen reseptor androgen antara kedua kelompok tersebut bermakna secara statistik (p = 0,031). Namun tidak ditemukan hubungan antara jumlah pengulangan CAG gen RA dengan konsentrasi sperma (rs = - 0,038; p = 0,775). Ini menunjukkan bahwa peningkatan jumlah pengulangan CAG gen RA bukan merupakan penyebab utama gangguan spermatogenesis. (Med J Indones 2004; 13: 215-20)

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Spermatogenesis impairment is the main cause of infertility in men. Androgen is believed to play a critical role in regulating spermatogenesis. Androgen acts by binding to the androgen receptor (AR) which is a protein regulator of DNA transcription. Exon 1 of AR gene contains a CAG repeat length polymorphism and it is believed to interfere AR function. This study includes DNA isolation from peripheral blood and amplification of CAG repeat fragments by PCR method. CAG repeat lengths were determined by electrophoresis on 6% denaturing gel polyacrylamide. We found that the mean CAG repeat lengths were 24,3 ± 3,4 in oligozoospermic/azoospermic men and 22,7 ± 2,7 in normozoospermic men. The difference in CAG repeat length between the two groups was statistically significant (p = 0,031, t-test). Nevertheless, there was no correlation between CAG repeat lengths and sperms concentration (rs = -0,038; p = 0,775). This result suggest that the expansion of CAG repeat length was not the main cause of spermatogenesis impairment. (Med J Indones 2004; 13: 215-20)"

"ABSTRAKTuberkulosis Multidrug Resistant (TB MDR) merupakan suatu masalah dan menjadi tantangan yang paling besar terhadap program pencegahan dan pemberantasan TB dunia. Angka kesembuhan pada TB MDR relatif lebih rendah dengan terapi yang lebih sulit, mahal, dan lebih banyak efek samping. Konversi kultur sputum M. tuberculosis dalam 2 bulan pengobatan dapat digunakan sebagai indikator luaran terapi dan target pertama dalam terapi TB MDR. Penelitian ini bertujuan untuk mengetahui hubungan antara gabungan derajat positivita sputum basil tahan asam (BTA), adanya kavitas paru, malnutrisi, diabetes mellitus (DM), dan kebiasaan merokok dengan konversi kultur sputum M. tuberculosis dalam 2 bulan pengobatan. Metode penelitian ini adalah penelitian khusus-kontrol dengan mengambil data sekunder dari penderita yang didiagnosis TB MDR di Klinik TB MDR Rumah Sakit Umum Pusat Dokter Hasan Sadikin pada periode April 2012 sampai dengan desember 2014. Kelompok kontrol adalah data pasien TB MDR yang mengalami konversi dalam 2 bulan pengobatan dan kelompok kasus adalah data pasien yang tidak mengalami konversi dalam 2 bulan pengobatan. Data analis dengan analisis univariat diikuti analisis multivariat regresi logistik. Hasilnya subjek penelitian berjumlah 190 orang, terbagi dalam kelompok kasus dan kontrol masing-masing 95 orang. Variabel bermakna pada analisis univariat adalah derajat positivitas sputum BTA, adanya kavitas paru, DM, dan malnutrisi. Analisis dilanjutkan dengan analisis multivariat regresi logistik dasn diperoleh hasil bahwa variabel yang berhubungan paling kuat dengan konversi kultut sputum BTA dalam 2 bulan pengobatan adalah derajat positivitas sputum BTA (Sputum BTA +1 p = 0,000, OR = 5,46; IK 95%:2,510-11, sputum BTA +2 p = 0,045, OR = 2.253; IK 95%: 1,017 - 4,989) dan adanya kavitas (p = 0,000, OR = 3,22; IK 95%: 1,61 - 6,45). Kesimpulannya derajat positivitas sputum BTA dan adanya kavitas memiliki hubungan yang paling kuat dengan konversi kultur sputum M. tuberculosis dalam 2 bulan pengobatan pada pasien TB MDR. "

"Polimorfisme gen reseptor vitamin D (RVD) merupakan kandidat genetik yang dapat menjelaskan rentannya suatu populasi terhadap tuberkulosis. Namun, hingga kini, sejumlah penelitian yang mencoba membuktikan hal tersebut menunjukkan hasil bervariasi pada berbagai populasi. Studi ini merupakan studi kasus-kontrol yang mengikutsertakan 35 pasien pascatuberkulosis paru (14 laki-laki dan 21 perempuan, median usia 40) serta 35 kontrol serumah (14 laki-laki dan 21 perempuan, median usia 39) yang tinggal di Nusa Tenggara Timur, salah satu provinsi di Indonesia dengan prevalensi tuberkulosis paru yang tinggi. Polimorfisme genetik diperiksa melalui metode polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) dengan menggunakan enzim restriksi BsmI dari sampel darah yang diisolasi dan ditambahkan EDTA. Sebaran frekuensi genotipe BsmI RVD pada kelompok kasus adalah BB=9 (26%), Bb=24 (69%), dan bb=2 (5%) sementara pada kelompok kontrol adalah BB=5 (14%), Bb=25 (72%), dan bb=5 (14%) dengan p=0,232 (OR 2,07, IK 95% 0,62-6,98). Distribusi frekuensi alel pada kelompok kasus adalah B=42 (60%) dan b=28 (40%) sementara pada kelompok kontrol adalah B=35 (50%) dan b=35 (50%). Frekuensi alel varian (alel b) pada penelitian ini adalah 0,45. Distribusi genotipe pada penelitian ini tidak memenuhi persamaan Hardy-Weinberg. Sebagai kesimpulan, penelitian ini tidak menunjukkan adanya hubungan antara polimorfisme gen RVD terhadap kejadian tuberkulosis paru.

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Vitamin D receptor gene (VDR) polymorphism is a genetic candidate which may explain the susceptibility of tuberculosis (TB) in a single population. However, until now, some studies which had tried to prove this showed varied results in different populations. This is a case-control study involving 35 post pulmonary tuberculosis patients (14 males and 21 females, median age 40) and 35 healthy household controls (14 males and 21 females, median age 39) who dwelled in East Nusa Tenggara, one of the provinces in Indonesia with high prevalence of pulmonary tuberculosis. The genetic polymorphism was examined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method with BsmI restriction enzyme from EDTA added-isolated blood sample. The distribution of VDR BsmI genotype frequency in case group was BB=9 (26%), Bb=24 (69%), and bb=2 (5%) whereas in control group was BB=5 (14%), Bb=25 (72%), and bb=5 (14%) with p=0.232 (OR 2.07, 95% CI 0.62-6.98). Furthermore, the distribution frequency of allele in case group was B=42 (60%) and b=28 (40%) whereas in control group was B=35 (50%) and b=35 (50%). Frequency of variant allele in this study was 0.45. Genotype distribution in this study did not meet the Hardy-Weinberg equilibrium. As conclusion, this study did not show any association between VDR gene polymorphism and pulmonary tuberculosis."

"In general, many studies have shown the association between TB and malnutrition. However, the mechanism between nutritional status and host defense in TB remains unclear, particularly the role of antioxidant status. This study was undertaken to investigate the antioxidant level (vitamin C, β-carotene, α-tocopherol), food intake and nutritional status in active pulmonary TB patients and healthy subjects."

"Latar belakang: Antigen38 Mycobacterium tuberculosis merupakan agen serodiagnostik yang potensial karena mengandungdua epitop spesifik untuk sel B. Mahalnya agen diagnostik menyebabkan lambatnya realisasi diagnosis TB secara cepat dinegara berkembang. Kami memproduksi antigen 38 rekombinan yang berasal dari galur lokal yang kemungkinan dapatdigunakan untuk memproduksi alat serodiagnostik TB yang ekonomis.Metode: Gen pab diisolasi dari pasien TB paru di Malang, diklon ke plasmid pGEM-Teasy menjadi pMB38. Klon E.coliDH5α yang membawa pMB38 diseleksi di medium yang ditambah dengan X-Gal. Ekspresi pab dilakukan menggunakanpMBhis yang berasal dari pPRoExHTc dibawah kontrol promoter Trc dengan inang E.coli DH5αHasil: Pencocokan sekuen gen pab dari klon E.coli DH5α berwarna putih dengan gen pab dari M. tuberculosisH37Rvmemperlihatkan homologi sebesar 98%. Protein rekombinan yang sudah dihilangkan signal peptidanya ditemukan disitoplasma.Kesimpulan: Gen pab dari pasien TB dapat diekspresikan secara intraseluler dengan sistem heterolog

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AbstractBackground: Mycobacterium tuberculosis antigen38 is a potent serodiagnostic agent containing two M. tuberculosisspecificB-cell epitopes. The high price of imported diagnostic agents hinders realization of fast clinical TB diagnosis indeveloping countries. Therefore, we produced recombinant antigen38 (recAg38M) from M. tuberculosis local strain, whichmight be used to produce economical tuberculosis serodiagnostic kit.Methods: Pab gene that was isolated from pulmonary TB patient in Malang was cloned into a plasmid vector (pGEMTeasy)to construct pMB38. The E.coli DH5α clone carrying pMb38 was selected on X-gal medium. The expression of pabwas mediated using pPRoExHTc under the control of Trc promoter and E.coli DH5α as host.Results: Alignment of the pab sequence from the white E.coli DH5α clones with that of M. tuberculosis H37Rv showed98% homology. The recombinant protein in which the signal peptide has been deleted to prevent the protein being secretedinto medium was found in the cytoplasm.Conclusion: pab gene of M. tuberculosis isolated from a TB patient could be expressed in heterologous system in E.coliDH5α."

"Nikotin adalah senyawa utama di dalam tembakau yang menimbulkan ketergantungan pada rokok. Nikotin diinaktivasi oleh tubuh menjadi kotinin melalui kerja enzim CYP2A6. Polimorfisme genetik CYP2A6 memegang peranan penting pada kebiasaan merokok dan ketergantungan pada nikotin. Telah diketahui terdapat alel gen CYP2A6*1A (wild type) yang berhubungan dengan metabolisme nikotin normal/cepat, dan beberapa variasi genetik seperti alel CYP2A6*4, CYP2A6*7, CYP2A6*9, CYP2A6*10, yang berkaitan dengan penurunan aktivitas metabolisme nikotin. Variasi aktivitas metabolisme nikotin ini berpengaruh pada kadar nikotin plasma. Perokok memerlukan kadar nikotin tertentu pada otaknya, sehingga pada individu dengan metabolisme nikotin yang cepat diperlukan jumlah rokok yang lebih banyak. Sebaliknya, pada individu dengan metabolisme nikotin yang lambat, nikotin plasma lambat diinaktivasi dan akan mengakibatkan gejala toksik, sehingga ketergantungan pada rokok menjadi lebih rendah.

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AbstractNicotine is a major addictive compound in tobacco cigarette smoke. After being absorbed by the lung nicotine is rapidly metabolized and mainly inactivated to cotinine by hepatic cytochrome P450 2A6 (CYP2A6) enzyme. Genetic polymorphisms in CYP2A6 may play a role in smoking behavior and nicotine dependence. CYP2A6*1A is the wild type of the CYP2A6 gene which is associated with normal or extensive nicotine metabolism. In the CYP2A6 gene, several polymorphic alleles have been reported such as CYP2A6*4, CYP2A6*7, CYP2A6*9, and CYP2A6*10 which are related to decreasing nicotine metabolism activity. The variation of nicotine metabolism activity could alter nicotine plasma levels. Smokers need a certain level of nicotine in their brain and must smoke regularly because of nicotine?s short half-life; this increases the number of smoked cigarettes in extensive metabolizers. Meanwhile, in slow metabolizers, nicotine plasma level may increase and results in nicotine toxicity. This will eventually lower the risk of dependence."