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Papers by Mariana Wahjudi

Direktorat PPI Ubaya, 2020

The governance of COVID-19 cases in Indonesia is carried out in accordance with the WHO direction... more The governance of COVID-19 cases in Indonesia is carried out in accordance with the WHO directions. Serological tests, often mentioned as rapid antibody tests, are used for mass screening testing while the polymerase-chain-reaction (PCR)-based tests are performed for routine confirmation of COVID-19 infection cases. PCR test is one of nucleic acid amplification tests (NAAT) for detection of viral RNA. The management of the COVID-19 detection caused controversies at the beginning of pandemic period. It seems that the controversies occurred due to misperception regarding the tests, as well as misunderstanding caused by differences in individual immune responses, viral dynamics in human bodies and clinical outcomes. In response to community opinion controversies, this paper discuss the following topics, i.e. a glimpse about COVID-19, the characteristics of SARS-CoV-2, viral dynamics in human body, the dynamics of human immune response to SARS-CoV-2, basic explanation about COVID-19 and SARS-CoV-2 testing, and the last part explained the occurred controversies.

Indonesian Journal of Clinical Pharmacy, 2016

Background: Uncontrolled asthma symptoms will exacerbate asthma. Aminofilin is now rarely used as... more Background: Uncontrolled asthma symptoms will exacerbate asthma. Aminofilin is now rarely used as asthma medication abroad because it shows major side effects, unlike in Indonesia, which is still widely used with relatively rare side effects events. Aminophylline have relatively more affordable price compared to salbutamol, the first-line option in the management of asthma exacerbations requirements. Both of these drugs have a risk of causing electrolyte disturbances, which could endanger the patients. Considering the individual drug side effects, so it important to study the safety of the medicine to ascertain whether there are differences in the incidence of electrolyte disturbances by both drugs. Objective: The main objective of this study was to determine differences in the incidence of electrolyte disturbances in patients with asthma exacerbations prescribed with aminophylline and salbutamol at a hospital in Surabaya. Method: This study design is a cross-sectional study of inpatient adult asthma exacerbations in emergency room (ER), using two groups, namely the group receiving intravenous aminophylline therapy (n = 22), and the group receiving nebulized salbutamol therapy (n = 21). Result: There is no significant difference between in intravenous aminophylline anda nebulized salbutamol group. And there is no significant difference in sodium (p>0,866) and potassium (p>0,470) level in blood as a respon to the asthma exacerbations treatment by intravenous aminophylline compared to nebulized salbutamol. Conclusion: Although there was no significant difference in the incidence of electrolyte disturbances in both drugs, but close monitoring is still needed to prevent any side effects incident.

Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi kada... more Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi kadar obat dalam darah serta berpengaruh terhadap kejadian adverse drug reaction (ADR) dan outcome klinis terapi asma. Frekuensi polimorfisme CYP1A2 diketahui bervariasi antar etnis. Diduga populasi Indonesia memiliki frekuensi varian gen CYP1A2*1F yang tinggi. Penelitian ini bertujuan untuk mengetahui profil polimorfisme gen CYP1A2*1F pada sampel nonasma dan asma di Indonesia dengan populasi lain berdasarkan literatur. Pengambilan data dilakukan pada Januari-Juni 2014. Sampel darah diperoleh dari 29 orang nonasma dan 16 pasien asma. Setelah dilakukan ekstraksi DNA genomik kemudian ditentukan polimorfisme gen CYP1A2*1F dengan metode PCR-RFLP. Hasil penelitian ini menunjukkan bahwa polimorfisme gen CYP1A2*1F pada sampel nonasma adalah 10,35% (3/29) untuk C/C, 37,93% (11/29) untuk C/A dan 51,72% (15/29) untuk A/A. Pada penderita asma frekuensi distribusi genotip C/A sebesar 81,25% (13/16) dan A/A sebesar 18,75% (3/16). Tidak terdapat perbedaan signifikan (p=0,276) frekuensi alel antara sampel nonasma dan pasien asma. Frekuensi gen CYP1A2*1F pada populasi Indonesia lebih besar dibandingkan dengan populasi Mesir, Jepang, dan Inggris akan tetapi lebih rendah dibandingkan dengan Malaysia. Oleh karena itu, dapat disimpulkan tidak terdapat perbedaan frekuensi.

Microbiology, 2011

The Pseudomonas aeruginosa PAO1 genome has at least two genes, pvdQ and quiP, encoding acylhomose... more The Pseudomonas aeruginosa PAO1 genome has at least two genes, pvdQ and quiP, encoding acylhomoserine lactone (AHL) acylases. Two additional genes, pa1893 and pa0305, have been predicted to encode penicillin acylase proteins, but have not been characterized. Initial studies on a pa0305 transposon insertion mutant suggested that the gene is not related to the AHL growth phenotype of P. aeruginosa. The close similarity (67 %) of pa0305 to HacB, an AHL acylase of Pseudomonas syringae, prompted us to investigate whether the PA0305 protein might also function as an AHL acylase. The pa0305 gene has been cloned and the protein (PA0305) has been overproduced, purified and subjected to functional characterization. Analysis of the purified protein showed that, like b-lactam acylases, PA0305 undergoes post-translational processing resulting in a-and b-subunits, with the catalytic serine as the first amino acid of the b-subunit, strongly suggesting that PA0305 is a member of the N-terminal nucleophile hydrolase superfamily. Using a biosensor assay, PA0305his was shown to degrade AHLs with acyl side chains ranging in length from 6 to 14 carbons. Kinetics studies using N-octanoyl-L-homoserine lactone (C 8 -HSL) and N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C 12 -HSL) as substrates showed that the enzyme has a robust activity towards these two AHLs, with apparent K cat /K m values of 0.14¾10 4 M "1 s "1 towards C 8 -HSL and 7.8¾10 4 M "1 s "1 towards 3-oxo-C 12 -HSL. Overexpression of the pa0305 gene in P. aeruginosa showed significant reductions in both accumulation of 3-oxo-C 12 -HSL and expression of virulence factors. A mutant P. aeruginosa strain with a deleted pa0305 gene showed a slightly increased capacity to kill Caenorhabditis elegans compared with the P. aeruginosa PAO1 wild-type strain and the PAO1 strain carrying a plasmid overexpressing pa0305. The harmful effects of the Dpa0305 strain on the animals were most visible at 5 days post-exposure and the mortality rate of the animals fed on the Dpa0305 strain was faster than for the animals fed on either the wild-type strain or the strain overexpressing pa0305. In conclusion, the pa0305 gene encodes an efficient acylase with activity towards longchain homoserine lactones, including 3-oxo-C 12 -HSL, the natural quorum sensing signal molecule in P. aeruginosa, and we propose to name this acylase HacB.

Microbiology, 2010

PvdQ, an acylase from Pseudomonas aeruginosa PAO1, has been shown to have at least two functions.... more PvdQ, an acylase from Pseudomonas aeruginosa PAO1, has been shown to have at least two functions. It can act as a quorum quencher due to its ability to degrade long-chain Nacylhomoserine lactones (AHLs), e.g. 3-oxo-C12-HSL, leading to a decrease in virulence factors. In addition, PvdQ is involved in iron homeostasis by playing a role in the biosynthesis of pyoverdine, the major siderophore of P. aeruginosa. In accordance with earlier studies on RNA level, we could show at the protein level that PvdQ is only expressed when iron is present at very low concentrations. We therefore set out to investigate the two functions of PvdQ under ironlimiting conditions. Gene deletion of pvdQ does not affect growth of P. aeruginosa but abrogates pyoverdine production, and results in an accumulation of 3-oxo-C12-HSL. Phenotypic analyses of our DpvdQ mutant at low iron concentrations revealed that this mutant is impaired in swarming motility and biofilm formation. Additionally, a plant and a Caenorhabditis elegans infection model demonstrated that the deletion of pvdQ resulted in reduced virulence. None of the phenotypes in the present study could be linked to the presence or absence of AHLs. These results clearly indicate that under iron-limiting conditions PvdQ plays a major role in swarming motility, in biofilm development and in infection that is more likely to be linked to the pyoverdine pathway rather than the LasI/LasR/3-oxo-C12-HSL quorum-sensing circuit.

European Journal of Pharmaceutical Sciences, 2013

In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic inf... more In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl-homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20°C and 55°C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55°C for at least 4 weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of ∼1.8 μm implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation.

Antimicrobial Agents and Chemotherapy, 2009

The Pseudomonas aeruginosa PAO1 gene pvdQ encodes an acyl-homoserine lactone (AHL) acylase capabl... more The Pseudomonas aeruginosa PAO1 gene pvdQ encodes an acyl-homoserine lactone (AHL) acylase capable of degrading N-(3-oxododecanoyl)-L-homoserine lactone by cleaving the AHL amide. PvdQ has been proven to function as a quorum quencher in vitro in a number of phenotypic assays. To address the question of whether PvdQ also shows quorum-quenching properties in vivo, an infection model based on the nematode Caenorhabditis elegans was explored. In a fast-acting paralysis assay, strain PAO1(pMEpvdQ), which overproduces PvdQ, was shown to be less virulent than the wild-type strain. More than 75% of the nematodes exposed to PAO1(pMEpvdQ) survived and continued to grow when using this strain as a food source. Interestingly, in a slow-killing assay monitoring the survival of the nematodes throughout a 4-day course, strain PAO1-⌬pvdQ was shown to be more virulent than the wild-type strain, confirming the role of PvdQ as a virulence-reducing agent. It was observed that larval stage 1 (L1) to L3-stage larvae benefit much more from protection by PvdQ than L4 worms. Finally, purified PvdQ protein was added to C. elegans worms infected with wild-type PAO1, and this resulted in reduced pathogenicity and increased the life span of the nematodes. From our observations we can conclude that PvdQ might be a strong candidate for antibacterial therapy against Pseudomonas infections.

Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi kada... more Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi
kadar obat dalam darah serta berpengaruh terhadap kejadian adverse drug reaction (ADR) dan outcome
klinis terapi asma. Frekuensi polimorfisme CYP1A2 diketahui bervariasi antar etnis. Diduga populasi
Indonesia memiliki frekuensi varian gen CYP1A2*1F yang tinggi. Penelitian ini bertujuan untuk
mengetahui profil polimorfisme gen CYP1A2*1F pada sampel nonasma dan asma di Indonesia dengan
populasi lain berdasarkan literatur. Pengambilan data dilakukan pada Januari–Juni 2014. Sampel darah
diperoleh dari 29 orang nonasma dan 16 pasien asma. Setelah dilakukan ekstraksi DNA genomik kemudian
ditentukan polimorfisme gen CYP1A2*1F dengan metode PCR-RFLP. Hasil penelitian ini menunjukkan
bahwa polimorfisme gen CYP1A2*1F pada sampel nonasma adalah 10,35% (3/29) untuk C/C, 37,93%
(11/29) untuk C/A dan 51,72% (15/29) untuk A/A. Pada penderita asma frekuensi distribusi genotip C/A
sebesar 81,25% (13/16) dan A/A sebesar 18,75% (3/16). Tidak terdapat perbedaan signifikan (p=0,276)
frekuensi alel antara sampel nonasma dan pasien asma. Frekuensi gen CYP1A2*1F pada populasi
Indonesia lebih besar dibandingkan dengan populasi Mesir, Jepang, dan Inggris akan tetapi lebih rendah
dibandingkan dengan Malaysia. Oleh karena itu, dapat disimpulkan tidak terdapat perbedaan frekuensi.

Direktorat PPI Ubaya, 2020

The governance of COVID-19 cases in Indonesia is carried out in accordance with the WHO direction... more The governance of COVID-19 cases in Indonesia is carried out in accordance with the WHO directions. Serological tests, often mentioned as rapid antibody tests, are used for mass screening testing while the polymerase-chain-reaction (PCR)-based tests are performed for routine confirmation of COVID-19 infection cases. PCR test is one of nucleic acid amplification tests (NAAT) for detection of viral RNA. The management of the COVID-19 detection caused controversies at the beginning of pandemic period. It seems that the controversies occurred due to misperception regarding the tests, as well as misunderstanding caused by differences in individual immune responses, viral dynamics in human bodies and clinical outcomes. In response to community opinion controversies, this paper discuss the following topics, i.e. a glimpse about COVID-19, the characteristics of SARS-CoV-2, viral dynamics in human body, the dynamics of human immune response to SARS-CoV-2, basic explanation about COVID-19 and SARS-CoV-2 testing, and the last part explained the occurred controversies.

Indonesian Journal of Clinical Pharmacy, 2016

Background: Uncontrolled asthma symptoms will exacerbate asthma. Aminofilin is now rarely used as... more Background: Uncontrolled asthma symptoms will exacerbate asthma. Aminofilin is now rarely used as asthma medication abroad because it shows major side effects, unlike in Indonesia, which is still widely used with relatively rare side effects events. Aminophylline have relatively more affordable price compared to salbutamol, the first-line option in the management of asthma exacerbations requirements. Both of these drugs have a risk of causing electrolyte disturbances, which could endanger the patients. Considering the individual drug side effects, so it important to study the safety of the medicine to ascertain whether there are differences in the incidence of electrolyte disturbances by both drugs. Objective: The main objective of this study was to determine differences in the incidence of electrolyte disturbances in patients with asthma exacerbations prescribed with aminophylline and salbutamol at a hospital in Surabaya. Method: This study design is a cross-sectional study of inpatient adult asthma exacerbations in emergency room (ER), using two groups, namely the group receiving intravenous aminophylline therapy (n = 22), and the group receiving nebulized salbutamol therapy (n = 21). Result: There is no significant difference between in intravenous aminophylline anda nebulized salbutamol group. And there is no significant difference in sodium (p>0,866) and potassium (p>0,470) level in blood as a respon to the asthma exacerbations treatment by intravenous aminophylline compared to nebulized salbutamol. Conclusion: Although there was no significant difference in the incidence of electrolyte disturbances in both drugs, but close monitoring is still needed to prevent any side effects incident.

Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi kada... more Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi kadar obat dalam darah serta berpengaruh terhadap kejadian adverse drug reaction (ADR) dan outcome klinis terapi asma. Frekuensi polimorfisme CYP1A2 diketahui bervariasi antar etnis. Diduga populasi Indonesia memiliki frekuensi varian gen CYP1A2*1F yang tinggi. Penelitian ini bertujuan untuk mengetahui profil polimorfisme gen CYP1A2*1F pada sampel nonasma dan asma di Indonesia dengan populasi lain berdasarkan literatur. Pengambilan data dilakukan pada Januari-Juni 2014. Sampel darah diperoleh dari 29 orang nonasma dan 16 pasien asma. Setelah dilakukan ekstraksi DNA genomik kemudian ditentukan polimorfisme gen CYP1A2*1F dengan metode PCR-RFLP. Hasil penelitian ini menunjukkan bahwa polimorfisme gen CYP1A2*1F pada sampel nonasma adalah 10,35% (3/29) untuk C/C, 37,93% (11/29) untuk C/A dan 51,72% (15/29) untuk A/A. Pada penderita asma frekuensi distribusi genotip C/A sebesar 81,25% (13/16) dan A/A sebesar 18,75% (3/16). Tidak terdapat perbedaan signifikan (p=0,276) frekuensi alel antara sampel nonasma dan pasien asma. Frekuensi gen CYP1A2*1F pada populasi Indonesia lebih besar dibandingkan dengan populasi Mesir, Jepang, dan Inggris akan tetapi lebih rendah dibandingkan dengan Malaysia. Oleh karena itu, dapat disimpulkan tidak terdapat perbedaan frekuensi.

Microbiology, 2011

The Pseudomonas aeruginosa PAO1 genome has at least two genes, pvdQ and quiP, encoding acylhomose... more The Pseudomonas aeruginosa PAO1 genome has at least two genes, pvdQ and quiP, encoding acylhomoserine lactone (AHL) acylases. Two additional genes, pa1893 and pa0305, have been predicted to encode penicillin acylase proteins, but have not been characterized. Initial studies on a pa0305 transposon insertion mutant suggested that the gene is not related to the AHL growth phenotype of P. aeruginosa. The close similarity (67 %) of pa0305 to HacB, an AHL acylase of Pseudomonas syringae, prompted us to investigate whether the PA0305 protein might also function as an AHL acylase. The pa0305 gene has been cloned and the protein (PA0305) has been overproduced, purified and subjected to functional characterization. Analysis of the purified protein showed that, like b-lactam acylases, PA0305 undergoes post-translational processing resulting in a-and b-subunits, with the catalytic serine as the first amino acid of the b-subunit, strongly suggesting that PA0305 is a member of the N-terminal nucleophile hydrolase superfamily. Using a biosensor assay, PA0305his was shown to degrade AHLs with acyl side chains ranging in length from 6 to 14 carbons. Kinetics studies using N-octanoyl-L-homoserine lactone (C 8 -HSL) and N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C 12 -HSL) as substrates showed that the enzyme has a robust activity towards these two AHLs, with apparent K cat /K m values of 0.14¾10 4 M "1 s "1 towards C 8 -HSL and 7.8¾10 4 M "1 s "1 towards 3-oxo-C 12 -HSL. Overexpression of the pa0305 gene in P. aeruginosa showed significant reductions in both accumulation of 3-oxo-C 12 -HSL and expression of virulence factors. A mutant P. aeruginosa strain with a deleted pa0305 gene showed a slightly increased capacity to kill Caenorhabditis elegans compared with the P. aeruginosa PAO1 wild-type strain and the PAO1 strain carrying a plasmid overexpressing pa0305. The harmful effects of the Dpa0305 strain on the animals were most visible at 5 days post-exposure and the mortality rate of the animals fed on the Dpa0305 strain was faster than for the animals fed on either the wild-type strain or the strain overexpressing pa0305. In conclusion, the pa0305 gene encodes an efficient acylase with activity towards longchain homoserine lactones, including 3-oxo-C 12 -HSL, the natural quorum sensing signal molecule in P. aeruginosa, and we propose to name this acylase HacB.

Microbiology, 2010

PvdQ, an acylase from Pseudomonas aeruginosa PAO1, has been shown to have at least two functions.... more PvdQ, an acylase from Pseudomonas aeruginosa PAO1, has been shown to have at least two functions. It can act as a quorum quencher due to its ability to degrade long-chain Nacylhomoserine lactones (AHLs), e.g. 3-oxo-C12-HSL, leading to a decrease in virulence factors. In addition, PvdQ is involved in iron homeostasis by playing a role in the biosynthesis of pyoverdine, the major siderophore of P. aeruginosa. In accordance with earlier studies on RNA level, we could show at the protein level that PvdQ is only expressed when iron is present at very low concentrations. We therefore set out to investigate the two functions of PvdQ under ironlimiting conditions. Gene deletion of pvdQ does not affect growth of P. aeruginosa but abrogates pyoverdine production, and results in an accumulation of 3-oxo-C12-HSL. Phenotypic analyses of our DpvdQ mutant at low iron concentrations revealed that this mutant is impaired in swarming motility and biofilm formation. Additionally, a plant and a Caenorhabditis elegans infection model demonstrated that the deletion of pvdQ resulted in reduced virulence. None of the phenotypes in the present study could be linked to the presence or absence of AHLs. These results clearly indicate that under iron-limiting conditions PvdQ plays a major role in swarming motility, in biofilm development and in infection that is more likely to be linked to the pyoverdine pathway rather than the LasI/LasR/3-oxo-C12-HSL quorum-sensing circuit.

European Journal of Pharmaceutical Sciences, 2013

In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic inf... more In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl-homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20°C and 55°C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55°C for at least 4 weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of ∼1.8 μm implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation.

Antimicrobial Agents and Chemotherapy, 2009

The Pseudomonas aeruginosa PAO1 gene pvdQ encodes an acyl-homoserine lactone (AHL) acylase capabl... more The Pseudomonas aeruginosa PAO1 gene pvdQ encodes an acyl-homoserine lactone (AHL) acylase capable of degrading N-(3-oxododecanoyl)-L-homoserine lactone by cleaving the AHL amide. PvdQ has been proven to function as a quorum quencher in vitro in a number of phenotypic assays. To address the question of whether PvdQ also shows quorum-quenching properties in vivo, an infection model based on the nematode Caenorhabditis elegans was explored. In a fast-acting paralysis assay, strain PAO1(pMEpvdQ), which overproduces PvdQ, was shown to be less virulent than the wild-type strain. More than 75% of the nematodes exposed to PAO1(pMEpvdQ) survived and continued to grow when using this strain as a food source. Interestingly, in a slow-killing assay monitoring the survival of the nematodes throughout a 4-day course, strain PAO1-⌬pvdQ was shown to be more virulent than the wild-type strain, confirming the role of PvdQ as a virulence-reducing agent. It was observed that larval stage 1 (L1) to L3-stage larvae benefit much more from protection by PvdQ than L4 worms. Finally, purified PvdQ protein was added to C. elegans worms infected with wild-type PAO1, and this resulted in reduced pathogenicity and increased the life span of the nematodes. From our observations we can conclude that PvdQ might be a strong candidate for antibacterial therapy against Pseudomonas infections.

Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi kada... more Polimorfisme genetik CYP1A2 berkaitan dengan metabolisme teofilin sehingga dapat memengaruhi
kadar obat dalam darah serta berpengaruh terhadap kejadian adverse drug reaction (ADR) dan outcome
klinis terapi asma. Frekuensi polimorfisme CYP1A2 diketahui bervariasi antar etnis. Diduga populasi
Indonesia memiliki frekuensi varian gen CYP1A2*1F yang tinggi. Penelitian ini bertujuan untuk
mengetahui profil polimorfisme gen CYP1A2*1F pada sampel nonasma dan asma di Indonesia dengan
populasi lain berdasarkan literatur. Pengambilan data dilakukan pada Januari–Juni 2014. Sampel darah
diperoleh dari 29 orang nonasma dan 16 pasien asma. Setelah dilakukan ekstraksi DNA genomik kemudian
ditentukan polimorfisme gen CYP1A2*1F dengan metode PCR-RFLP. Hasil penelitian ini menunjukkan
bahwa polimorfisme gen CYP1A2*1F pada sampel nonasma adalah 10,35% (3/29) untuk C/C, 37,93%
(11/29) untuk C/A dan 51,72% (15/29) untuk A/A. Pada penderita asma frekuensi distribusi genotip C/A
sebesar 81,25% (13/16) dan A/A sebesar 18,75% (3/16). Tidak terdapat perbedaan signifikan (p=0,276)
frekuensi alel antara sampel nonasma dan pasien asma. Frekuensi gen CYP1A2*1F pada populasi
Indonesia lebih besar dibandingkan dengan populasi Mesir, Jepang, dan Inggris akan tetapi lebih rendah
dibandingkan dengan Malaysia. Oleh karena itu, dapat disimpulkan tidak terdapat perbedaan frekuensi.