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Identification of point mutations in Glucose-6-Phosphate Dehydrogenase gene in Timor Island people : A preliminary report Hardjowasito, Widanto; Pardjianto, Bambang; Fitri, Loeki E.; Ys, Mardhani; M., Loekito R.; Shirakawa, Taku; Nishiyama, Kaoru; Matsuo, Masafumi
Medical Journal of Indonesia Vol 10, No 4 (2001): October-December
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (493.394 KB) | DOI: 10.13181/mji.v10i4.35

Abstract

Glucose 6 phosphate dehydrogenase (G6PD) deficiency is common in malaria endemic region, however no molecular study has been performed on G6PD deficiency in Timor Island, Indonesia a malarial hyperendemic area which Proto Malay is the majority of the people in that island. To observe the frequency and molecular type of mutations in G6PD deficient Proto Malay people, 118 native people were screened using formazan ring test. Mutation in the G6PD gene were determined by MPTP (Multiple PCR using Multiple Tandem Forward Primers and a common Reserve Pimer) method and confirmed by automatic sequencer. This study shows that three males have lower G6PD activity. Using MPTP method, a point mutation could be indicated in the two cases. Sequencing of the amplified products in 2 G6PD patients disclosed mutations of T383C in exon 5 and C 592 T in exon 6 in respective case. Our result documents point mutations in exon 5 and exon 6 in the G6PD gene of two Proto Malay people in Timor. These mutations are common in Asia region. (Med J Indones 2001; 10: 210-3)Keywords: mutations, G6PD, Proto Malay.
Effect of N-Acetyl Cysteine administration to the degree of parasitemia and plasma interleukin-12 level of mice infected with plasmodium berghei and treated with artemisinin Fitri, Loeki E.; Rosyidah, Hannatur; Sari, Nur P.; Endarti, Agustina T.
Medical Journal of Indonesia Vol 18, No 1 (2009): January-March
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (435.717 KB) | DOI: 10.13181/mji.v18i1.332

Abstract

Introduction Protection against malaria requires a cell-mediated immune response which is initiated by releasing interleukin-12 (IL-12) from antigen presenting cells (APC). N-Acetyl Cysteine (NAC) is a precursor of glutathione, while glutathione itself increases IL-12 production. Treatment with NAC combined with artemisinin is supposed to increase cellular immunity of mice during Plasmodium berghei infection. The aim of this study was to measure the effects of NAC administration on the degree of parasitemia and plasma IL-12 level in mice infected with P. berghei and treated with artemisinin.Methods The research was done using post-test-control-only design using 5 groups: group A (negative control group), group B (positive control group, or mice infected with P.berghei without therapy), group C ( mice infected by P.berghei and received artemisinin 0.04 mg/g BW for 7 days), group D (mice infected with P.berghei and received artemisinin in combination with NAC 1 mg/g BW for 7 days) and group E (mice infected wirth P.berghei and received artemisinin in  combination with NAC 1 mg/g BW for 3 days and tapered into ½ mg/g BW for 4 days). Parasitemia was followed up every two days. Approximately six days post infection or when the degree of parasitemia reached ± 10% therapy was begun. On the 3rd, 5th, and 7th days post therapy, mice from each group were terminated and assayed for plasma IL-12 level (ELISA, Bender Medsystems GmbH, Vienna, cat. BMS6004).Results All mice treated with artemisinin mono-therapy and combined therapy had significantly decreased parasitemia (P=0.000). There was no significant difference (P>0.05) in decreasing parasitemia among treatment groups. The plasma IL-12 level increased significantly in both groups that received the combination of artemisinin and NAC constant dose and tapering dose compared with the group that received artemisinin mono-therapy (p < 0,05). Plasma IL-12p70 level in the combination of artemisinin and NAC tapering dose therapy group was higher than other groups on the 5th and 7th days post therapy.Conclusion The conclusion of this research is that artemisinin mono-therapy decreased parasitemia effectively as well as the combination therapy of artemisinin and NAC. Artemisinin and NAC therapy, constant and tapering dose, increase plasma IL-12p 70 level more than artemisinin mono-therapy does. The highest plasma IL-12p70 level was found in the artemisinin plus NAC tapering dose therapy group with seven days duration of therapy. (Med J Indones 2009; 18: 5-9)Keywords: N-acetyl Cysteine, Parasitemia, Interleukin-12, Plasmodium berghei
Expression of inducible nitric oxide synthase, caspase-3 and production of reactive oxygen intermediate on endothelial cells culture (HUVECs) treated with P. falciparum infected erythrocytes and tumour necrosis factor-α Fitri, Loeki E.
Medical Journal of Indonesia Vol 15, No 3 (2006): July-September
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (452.992 KB) | DOI: 10.13181/mji.v15i3.227

Abstract

Cytoadherence of P. falciparum infected erythrocytes on endothelial cells is a key factor in development of severe malaria. This process may associated with the activation of local immune that was enhanced by tumour necrosis factor-α (TNF-α). This study was conducted to see the influence of P.falciparum infected erythrocytes cytoadherence and TNF-α treatment in inducing endothelial cells activation in vitro. inducible nitric oxide synthase (iNOS) and caspase-3 expression, also reactive oxygen intermediate (ROI) production were used as parameters. An Experimental laboratory study had been done to observe endothelial cells activation (HUVECs) after treatment with TNF-α for 20 hours or P. falciparum infected erythrocytes for 1 hour or both of them. Normal endothelial cells culture had been used as a control. Using immunocytochemistry local immune activation of endothelial cells was determined by iNOS and caspase-3 expression. Nitro Blue Tetrazolium reduction-assay was conducted to see the ROI production semi quantitatively. inducible nitric oxide synthase expression only found on endothelial cells culture treated with P. falciparum infected erythrocytes or both P. falciparum infected erythrocytes and TNF-α. Caspase-3 expression found slightly on normal endothelial cells culture. This expression increased significantly on endothelial cells culture treated with both P.falciparum infected erythrocytes and TNF-α (p=0.000). The normal endothelial cells release low level of ROI in the presence of non-specific trigger, PMA. In the presence of P. falciparum infected erythrocytes or TNF-α or both of them, some cells showed medium to high levels of ROI. Cytoadherence of P. falciparum infected erythrocytes and TNF α treatment on endothelial cells can induce activation of local immune marked by increase inducible nitric oxide synthase and release of free radicals that cause cell damage. (Med J Indones 2006; 15:151-6) Keywords: P.falciparum ,HUVECs, TNF-α, iNOS, Caspase-3, ROI
Inhibition of B-cell activating factor activity using active compounds from Physalis angulata in the mechanism of nephrotic syndrome improvement: A computational approach Kardani, Astrid K.; Fitri, Loeki E.; Samsu , Nur; Subandiyah , Krisni; Endharti, Agustina T.; Nugrahenny, Dian; Wibowo, Syahputra
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.859

Abstract

Nephrotic syndrome, a multifaceted medical condition characterized by significant proteinuria, has recently prompted a reorientation of research efforts toward B-cell-mediated mechanisms. This shift underscores the pivotal role played by B-cells in its pathogenesis. The aim of this study was to explore potential therapeutic pathways, with specific attention given to compounds found in Physalis angulata, including withanolides, such as physalins, which constitute one of the five distinct withanolide subgroups identified in Physalis angulata. Furthermore, the study assessed the monoclonal antibody belimumab, designed to target B-cell activating factor (BAFF) and its associated receptors (TACI, BCMA, and BAFF-R). Various research techniques were employed, encompassing data mining, bioactivity analysis, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling, molecular modeling, and docking studies. Withanolide was demonstrated as a potential inhibitor for the protein BAFF, showing a binding energy of -7.1 kcal/mol. Physalin F emerged as the leading candidate inhibitor for the protein TACI, with a binding energy of -8.3 kcal/mol. Similarly, withanolide was identified as the top inhibitor candidate for the protein BCMA, exhibiting a binding energy of -7.0 kcal/mol. The most favorable interaction with BAFF-R was physalin F, which displayed a binding energy of -8.0 kcal/mol. Moreover, molecular dynamic simulation suggested that physalin F was able to maintain protein stability, hence being a good inhibitor candidate for BAFF-R and TACI proteins. The results of this investigation demonstrated substantial promise, indicating that these withanolides and withaphysalin A compounds derived from Physalis angulata offer alternative avenues for B-cell targeting. Consequently, this study presents opportunities for pioneering treatments in the management of nephrotic syndrome.