Syakib Bakri
Postgraduate Program in Biomedics, Hasanuddin University Jl. Perintis Kemerdekaan Km.10, Makassar

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Altered Level of Soluble fms-like Tyrosine Kinase 1 (sFlt1) and Hypoxia Inducible Factor-1alpha (HIF-1alpha) in Normotensive Pregnancy and Preeclampsia John Wantania; Syakib Bakri; Karel Pandelaki; Maisuri Chalid
The Indonesian Biomedical Journal Vol 5, No 2 (2013)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v5i2.61

Abstract

BACKGROUND: Preeclampsia is still a significant problem worldwide. Of the many suggested mechanisms of its pathogenesis, the latest one is the balance of angiogenic factor and its relationship with hypoxia factors. The objective of this study was to observe changes or dynamic process of soluble fms-like tyrosine kinase 1 (sFlt1) as anti-angiogenic factor and hypoxia inducible factor 1-alpha (HIF-1α) as hypoxia marker in normotensive pregnancy and preeclampsia in mid-term and full-term pregnancies.METHODS: A cohort study was conducted on 36 normotensive subjects, first examination was conducted at 20-28 weeks of gestation. Then second examination was conducted at the time of preeclampsia diagnosed or full-term pregnancy. Preeclampsia was characterized by hypertension of systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, with two readings separated in 4-6 hours period, and/or proteinuria with urine dipstick of ≥1+ or ≥300 mg per 24 hours. Examinations of sFlt-1 and HIF-1α were done by enzyme-linked immunosorbent assay method. Statistical analysis was done using a significance level of p<0.05.RESULTS: Concentration of sFlt-1 was elevated in normotensive pregnancy and preeclampsia. Higher sFlt-1 concentration elevation was seen in preeclamptic group comparing to normotensive group, although not significant. This finding was related to the fact that investigated subjects were mostly developing mild preeclampsia merely. Comparing to normotensive group, preeclamptic group had higher HIF-1α concentration-per-week elevation, but not significant. There was a positive correlation between concentrations of sFlt-1 and HIF-1α, but not significant.CONCLUSION: sFlt-1 concentration elevation was correlated with preeclampsia. Therefore comparing to averages, changes of sFlt-1 concentrations were more important. Concentrations of HIF-1α and sFlt-1 were positively correlated.KEYWORDS: sFlt-1, HIF-1α, preeclampsia, normotension
Role of 8-isoprostane, Matrix Gla Protein (MGP) and Bone Morphogenetic Protein-2 (BMP-2) in Vascular Calcification in Chronic Kidney Disease Wiwik Rositawati; Syakib Bakri; Gatot Susilo Lawrence; Andi Wijaya
The Indonesian Biomedical Journal Vol 5, No 2 (2013)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v5i2.71

Abstract

BACKGROUND: Vascular calcification may be an important risk factor of cardiovascular disease in Chronic Kidney Disease (CKD). The pathobiology of vascular calcification in CKD is complex and involves some factors including inflammation, oxidative stress and balancing of calcification regulators. The aim of the study was to investigate the interaction between 8-isoprostane with calcification regulators such as matrix gla protein (MGP) and bone morphogenetic protein (BMP)-2 with vascular calciication in CKD.METHODS: A cross-sectional study was performed on 63 subjects undergoing haemodialysis maintenance for more than 3 months. Abdominal aortic calcification (AAC) was measured using a lateral abdominal X-ray for calcification in abdominal aorta, which is related to severity of calcific deposits at lumbar vertebral segment (L)1-L4. Serum levels of 8-isoprostane, MGP and BMP-2 were measured by enzyme-linked immunosorbent assay method.RESULTS: Results showed that 8-isoprostane levels were correlated with BMP-2 (r=0.266, p=0.018) and MGP levels (r=0.410, p≤0.001). MGP/BMP-2 levels ratio was correlated with AAC score (r=0.279, p=0.013). Subjects were then stratified into 3 groups based on AAC score: 0, 1-6 and ≥7. The highest mean of MGP levels was in AAC score 1-6 group, and the highest mean of 8-isoprostane levels was in AAC score ≥7. In the group of AAC score 0, 8-isoprostane levels were correlated with MGP levels (r=0.499, p=0.001) and MGP/BMP-2 levels ratio (r=0.291, p=0.034). In AAC score 1-6 group, 8-isoprostane levels were correlated with BMP-2 (r=0.661, p=0.005) and MGP levels (r=0.569, p=0.017). In AAC score ≥7 group, MGP levels were positively correlated with AAC score (r=0.608, p=0.041). With multivariate logistic regression analyses, we identified that increased MGP/BMP-2 levels ratio (OR=12.436; 95% CI=1.595-96.971) was an independent predictor in aortic calcification event.CONCLUSION: We concluded that regulators of calcification including calcification inhibitor and promoter related to oxidative stress, were associated with vascular calcification in CKD. MGP levels were increased in the early of calcification and MGP/BMP-2 levels ratio was a strong predictor for vascular calcification in CKD.KEYWORDS: vascular calcification, CKD, oxidative stress, 8-isoprostane, MGP, BMP-2