Ramdan Panigoro

HPV Genotyping Linear Assay Test Comparison in Cervical Cancer Patients: Implications for HPV Prevalence and Molecular Epidemiology in a Limited-resource Area in Bandung, Indonesia

BACKGROUND Persistent infection with high risk human papillomavirus (hrHPV) is strongly associated with cervical cancer. Normal cervical cells may also harbor hrHPV, and detection of early hrHPV infection may minimize risk of cervical cancer development. This study aimed to compare two commercial HPV genotyping assays that may affordable for early screening in a limited-resource setting in Bandung, Indonesia. MATERIALS AND METHODS DNA from cervical biopsies with histologically confirmed as squamous cell cervical cacinoma were HPV genotyped by Linear Assay 1 (Roche Diagnostics, Mannheim, Germany) or Linear Assay 2 (Digene HPV Genotyping RH Test, Qiagen Gaithersburg, MD). In a subset of samples of each group, HPV genotype results were then compared. RESULTS Of 28 samples genotyped by linear assay 1, 22 (78.6%) demonstrated multiple infections with HPV-16 and other hrHPV types 18, 45 and/or 52. In another set of 38 samples genotyped by linear assay 2, 28 (68.4%) were mostly single infections by hrHPV type 16 or 18. Interestingly, 4 samples that had been tested by both kits showed discordant results. CONCLUSIONS In a limited-resource area such as in Indonesia, country with a high prevalence of HPV infection a reliable cervical screening test in general population for early hrHPV detection is needed. Geographical variation in HPV genotyping result might have impacts for HPV prevalence and molecular epidemiology as the distribution in HPV genotypes should give clear information to assess the impact of HPV prophylactic vaccines.

Low Hemoglobin among Pregnant Women in Midwives Practice of Primary Health Care, Jatinangor, Indonesia: Iron Deficiency Anemia or β-Thalassemia Trait?

Low hemoglobin (Hb) or anemia is common among pregnant women in developing countries which may cause adverse pregnancy outcomes and maternal deaths. Our study aimed to assess Hb level measured by midwives in primary health care facility at rural area of Jatinangor, Indonesia, and to explore whether the anemia was due to iron deficiency (IDA) or β-thalassemia trait (β-TT). Pregnant women (n = 105) had finger prick test for Hb level during a regular antenatal care examination from October to November 2016. Hb level by finger prick test was compared with venous blood, measured by complete blood count (CBC). Indices including MCV and MCH and indices of Shine & Lal, Mentzer, Srivastava, Engels & Frase, Ehsani, and Sirdah were analyzed to differentiate anemia due to IDA and anemia due to suspect β-TT. HbA2 was measured to confirm β-TT. Anemic pregnant women were found in 86.7% by finger prick test compared to 21.9% (n = 23) by CBC. The prevalence of β-TT in our study was 5.7%. Hb measurement among pregnant women in low resource area is highly important; however, finger prick test in this study showed a high frequency of anemia which may lead to iron oversupplementation. A standard CBC is encouraged; MCV and MCH would help midwives to identify β-TT.

Iron chelating activity of Caesalpinia sappan L. extract on iron status in iron overload rats (Rattus norvegicus L.)

Sappanwood (Caesalpinia sappan L.) is already known as an anti chelating iron property by its flavonoids and brazilin compounds in iron overload rats (Rattus norvegicus L.) model. However, its optimal dosage need to be determine of optimizing its effect. The purpose of this study was to determine the dose of sappanwood extract as iron chelating agents. This study was conducted using a completely randomized design (CRD) of 27 Wistar rats. The rats were divided into nine groups: rats were given aquades as negative control 1 (KN1), CMC as a control 2 (KN2), iron dextran dose of 60 mg · kg−1 bw (body weight) (KP) as positive control, iron dextran with deferiprone dose of 75 mg · kg−1 bw (P1), iron dextran with sappanwood extract dose 100 mg · kg−1 bw (P2), 200 mg · kg−1 bw (P3), 300 mg · kg−1 bw (P4), and 400 mg · kg−1 bw (P5), iron dextran with a dose of 400 mg · kg−1 bw (satellite) (P6) and, administered orally for 28 days treatment. The iron status such as ferritin, transferrin, iron liver, serum iron, Total Iron Binding Capacity (TIBC), and transferrin saturation were measured. The data were analyzed using analysis of variance (ANOVA) with the level of confidence interval (CI) 95 % (α = 0.05) and difference then tested using Duncan multiple range test (MRT). The results showed that sappanwood extract at dose 200 mg · kg−1 bw can decrease ferritin, iron liver, and iron serum as 24.9 %, 54.08 %, 38.9 % and increased transferrin saturation, transferrin level, and TIBC as 78.22 %, 102.27 % respectively. This dose was evaluated as the most effective iron chelating propertiesSappanwood (Caesalpinia sappan L.) is already known as an anti chelating iron property by its flavonoids and brazilin compounds in iron overload rats (Rattus norvegicus L.) model. However, its optimal dosage need to be determine of optimizing its effect. The purpose of this study was to determine the dose of sappanwood extract as iron chelating agents. This study was conducted using a completely randomized design (CRD) of 27 Wistar rats. The rats were divided into nine groups: rats were given aquades as negative control 1 (KN1), CMC as a control 2 (KN2), iron dextran dose of 60 mg · kg−1 bw (body weight) (KP) as positive control, iron dextran with deferiprone dose of 75 mg · kg−1 bw (P1), iron dextran with sappanwood extract dose 100 mg · kg−1 bw (P2), 200 mg · kg−1 bw (P3), 300 mg · kg−1 bw (P4), and 400 mg · kg−1 bw (P5), iron dextran with a dose of 400 mg · kg−1 bw (satellite) (P6) and, administered orally for 28 days treatment. The iron status such as ferritin, transferrin, iron liver, serum iron, Tot...

Status Asetilator Gen NAT2 pada Pasien Tuberkulosis dan Tuberkulosis dengan Diabetes Melitus di Kupang, Nusa Tenggara Timur

Indonesia adalah negara dengan jumlah penderita tuberkulosis (TB) terbanyak kedua di dunia. Diabetes melitus (DM) merupakan salah satu komorbid TB. Arylamine N-acetyltransferase 2 (NAT2) adalah enzim yang berfungsi memetabolisir isoniazid (INH) yang disandi oleh gen NAT2 . Gen NAT2 memiliki sejumlah polimorfisme dan dapat menentukan kemampuan seseorang untuk memetabolisir obat yang disebut status asetilator. Pada individu dengan status asetilator lambat, INH dimetabolisir dengan lambat sehingga memungkinkan terjadi intoksikasi hati. Pada TB dengan DM (TBDM) status asetilator lambat dapat membuat pengobatan TB maupun DM menjadi kurang optimal. Penelitian ini bertujuan mengeksplorasi status asetilator pasien TBDM di RSUD Prof. WZ Johannes Kupang periode Juni–November 2011. Pada penelitian potong lintang ini DNA dari darah 122 pasien TB diisolasi dan gen NAT2 kemudian diamplifikasi dan disekuensing untuk diketahui status asetilatornya. Hasil penelitian menunjukkan terdapat 5 pasien yang memiliki glukosa serum >200 mg/dL yang dikategorikan sebagai pasien TBDM. Pada pasien TBDM didapatkan seorang dengan status asetilator cepat (NAT2*4/NAT2*4), 2 orang dengan status asetilator sedang (NAT2*13A/NAT2*6J), dan 2 orang dengan status asetilator lambat (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B). Pada pasien TB yang dipilih secara random berdasar usia dan jenis kelamin serupa dengan TBDM didapatkan 2 orang dengan status asetilator cepat (NAT2*4/NAT2*4) dan 3 orang dengan asetilator sedang (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J). TBDM yang memiliki status asetilator lambat berpotensi memiliki masalah ganda dalam terapi, selain dapat terjadi toksisitas hati akibat terapi dengan INH, juga dapat mengakibatkan pengobatan DM menjadi tidak optimal. Perlu dilakukan peneltian lebih lanjut terkait farmakogenetik pada TBDM. [ MKB. 2016;49(1):61–6] Kata kunci : Asetilator, isoniazid, NAT2 , farmakogenetik, tuberkulosis NAT2 Gene Acetylator Status of Tuberculosis and Tuberculosis with Diabetes Mellitus Patients in Kupang, Nusa Tenggara Timur Indonesia is the second highest country with TB patients in the world. Diabetes mellitus (DM) is a comorbid of TB. Arylamine N-acetyltransferase 2 (NAT2), encoded by the NAT2 gene, is an enzyme that metabolizes isoniazid (INH). NAT2 gene has some polimorphysims that may play a role in INH acetylating process. Those who are slow acetylators may develop liver intoxication as a consequence of slow INH metabolism process. Slow acetylator TBDM patients may complicate both TB and DM treatment, causing them to be less optimal. The aim of this study was to explore the acetylator status of TBDM patients in Kupang, Indonesia. A cross-sectional study was conducted by obtaining DNA of 122 TB patients in Kupang in June–November 2011. NAT2 gene was amplified and sequenced to determine the acetylator status. There were 5 TB patients who had a glucose serum level of >200mg/dL and was catagorized as TBDM. Result showed that there was 1 TBDM patient who was a rapid acetylator (NAT2*4/NAT2*4), 2 patients as intermediate acetylators (NAT2*13A/NAT2*6J), and 2 patients as slow acetylators (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B). Meanwhile, there were 2 TB patients who was rapid acetylators (NAT2*4/NAT2*4) and 3 patients as intermediate acetylators (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J). Slow NAT2 acetylator TBDM patients potentially face more problems during therapy. As INH may cause liver intoxication, these patients may also experience unoptimum DM treatment. Therefore, it is strongly recommended to do a study on the role of pharmacogenomics in TBDM. [ MKB. 2016;49(1):61–6] Key words: Acetylator, isoniazid, NAT2 , pharmacogenetics, tuberculosis