Ani Melani Maskoen

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...

UGT1A1 Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population

Neonatal hyperbilirubinemia (NH) is a common finding in newborn babies in Indonesia. Common and rare variants of UGT1A1 have been known to contribute to NH etiology. This study aims to identify UGT1A1 genetic variation and haplotype associated with NH in Indonesian population. DNA was isolated from 116 cases and 115 controls and a targeted-deep sequencing approach was performed on the promoter, UTRs, and exonic regions of UGT1A1. Determining association of common variants and haplotype analysis were performed using PLINK and Haploview. Ten and 4 rare variants were identified in cases and controls, respectively. The UGT1A1 rare variants frequency in cases (5.17%) was higher than that in controls (1.7%). Four of those rare variants in cases (p.Ala61Thr, p.His300Arg, p.Lys407Asn, and p.Tyr514Asn) and three in controls (p.Tyr79X, p.Ala346Val, and p.Thr412Ser) are novel variants. The frequencies of p.Gly71Arg, p.Pro229Gln, and TA7 common variants were not significantly different between cases and controls. A haplotype, consisting of 3 major alleles of 3′ UTRs common variants (rs8330C>G, rs10929303C>T, and rs1042640C>G), was associated with NH incidence (p = 0.025) in this population. Using targeted-deep sequencing and haplotype analysis, we identified novel UGT1A1 rare variants and disease-associated haplotype in NH in Indonesian population.

TGFß3 / SfaN1 gene variant and the risk factor of nonsyndromic cleft palate only among Indonesian patients

Non-syndromic cleft palate only (NS CPO) is one of the most common congenital malformations that affect between 1 in 1000 - 2500 live births worldwide. The etiopathogenesis of clefts including NS CPO has been widely studied but is still poorly understood. NS CPO is considered to be a genetically complex, multifactorial disease. Based on several studies, mutations of TGFβ3 gene emerged as the strong candidate gene associated with NS CPO. The purpose of this study was to analyze the relationship between the TGFβ3 / SfaN1 gene variant and the risk of NS CPO in Indonesian patients. This study was case control design using samples from 31 NS CPO subjects and 35 control subjects. DNA was extracted from venous blood and the segment of TGFβ3 gene/ SfaN1 were amplified by using polymerase chain reaction (PCR) technique, then digestion products by SfaN1 restriction enzyme which can detect locus of gene variant / polymorphism from restriction fragment length polymorphisms (RFLP) method were evaluated. The results indicated that the gene variant as substitution of base G into A was identified in TGFβ3 gene and the frequency of heterozygous mutant GA genotype was 63,6% in NS CPO subjects and 36,4% in control subjects. The frequency of heterozygous mutant GA genotype was associated with increased risk of NS CPO (odds ratio (OR) = 2,260, 95% CI = 0,592 - 8,625). In conclusion, TGFβ3 gene / SfaN1 polymorphism can be considered as the risk factor associated with NS CPO in Indonesian patients.

Cornelia de lange syndrome with thyroid agenesis of an indonesian patient

Cornelia de Lange syndrome (CdLs), which is also called Brachmann de Lange syndrome, is a congenital disorder characterized by distinctive facial features, prenatal and postnatal growth deficiency, feeding difficulties, psychomotor delay, behavioral problems, and associated malformations that mainly involve the upper extremities. The prevalence ranges from 1:100,000 to as high as 1:10,000. Most cases (50-60%) were carried mutation in NIPBL gene. To our knowledge this is the first CdLs Indonesian case that reported with molecular analysis study. We present an 11 months old female Indonesian patient with classic CdLs with congenital hypothyroid. Genetics studies were performed in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Thyroid studies (T3, T4, TSH and thyroid scan) were performed. Low level of T3 and T4, and high level of TSH were observed. Thyroid agenesis was found in thyroid scan examination. We detected thyroid agenesis which has been never reported in CdLs patients. We could not find any mutation in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Further genetics examinations were necessary whether there is mutation in other locus.