Efek Suplemen L-Arginin Subakut Peroral Pada Kontraksi Aorta Tikus Diabetes

Penelitian ini bertujuan untuk mengetahui pengaruh suplemen L-arginin subakut peroral pada tikus diabetes-streptozotosin terhadap respons kontraksi aorta melalui mekanisme pencegahan peningkatan stress oksidatif. L-arginine diberikan selama 8 minggu pada tikus diabetes dengan dosis 10, 100 dan 1000 mg.kg-1 BB.hari-1. Parameter yang diukur adalah MDA-plasma untuk menilai oksidatif stress dan teknik bioassay dengan isolasi organ terpisah aorta ring untuk menilai respons reseptor adrenergik-a1 di otot polos aorta terhadap fenilefrin (PE). Dari respons kontraksi aorta dapat diketahui nilai Emaks dan pD2 PE. Hasil penelitian menunjukkan bahwa pemberian L-arginin 100, 1000 mg.kg-1 BB.hari-1 pada tikus diabetes dapat mencegah peningkatan MDA-plasma (p<0.001). Pemberian L-arginin dosis 100, 1000 mg.kg-1 BB.hari-1 dapat mencegah peningkatan respons kontraksi aorta terhadap PE melalui pencegahan peningkatan Emaks (p<0.000) dan menurunkan pD2 pada dosis 1000 mg.kg-1 BB.hari-1 (p<0.001). Hasil Jalur Hubungan menunjukkan pencegahan peningkatan Emaks melalui jalur pencegahan peningkatan MDA (p<0.012) dan penurunan pD2 melalui jalur langsung (p<0.016). Berdasarkan haasil penelitian dapat disimpulkan bahwa pemberian suplemen L-arginin pada tikus diabetes dapat mencegah peningkatan respons kontraksi aorta terhadap PE dengan cara: (1) mencegah peningkatan Emaks melalui pencegahan peningkatan MDA (jalur tidak langsung); dan (2) secara langsung menurunkan afinitas reseptor adrenergik-a1

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided. This article is protected by copyright. All rights reserved

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to alpha-aminoadipic semialdehyde dehydrogenase deficiency

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided. This article is protected by copyright. All rights reserved

Glycerol Hypersensitivity in a Drosophila Model for Glycerol Kinase Deficiency Is Affected by Mutations in Eye Pigmentation Genes

Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency

Efek Penambahan Laktulosa pada Susu Formula Bayi: Tinjauan Sistematik

Pendahuluan: Salah satu komponen terbesar dalam air susu ibu (ASI) adalah oligosakarida. Oligosakarida berperan penting pada saluran cerna bayi melalui efek prebiotiknya. Laktulosa sebagai salah satu oligosakarida sintetis, telah dikategorikan sebagai prebiotik dan memiliki efek menyerupai ASI dalam hal mengubah komposisi mikrobiota usus. Metode: Tinjauan sistematis efek penambahan laktulosa ke dalam susu formula bayi. Hasil: Laktulosa bisa memperbaiki konsistensi dan frekuensi tinja, hingga menyerupai tinja bayi yang mendapat ASI. Efek simpang campuran prebiotik yang sering ditemui adalah diare, kembung dan muntah. Simpulan: Masih diperlukan penelitian lebih lanjut untuk merekomendasikan penambahan laktulosa secara rutin pada susu formula bayi.Introduction. One of the largest components of breast milk is human milk oligosaccharides (HMO). These components play an important role in the infant gastrointestinal tract based on their prebiotic effect. Lactulose is one of synthetic oligosaccharides, categorized as prebiotic; its effect resembles breastmilk in altering intestinal microbiota composition. Method. A systematic review on the effects of lactulose addition to infant formula. Results. Our search indicates that lactulose can improve the consistency and frequency of feces to resemble the stools of breast-fed infants. Adverse effects of mixed prebiotics are diarrhea, bloating and vomiting. Conclusion. Further research is still needed. Routine addition of lactulose in infant formula is not yet recommended

Mutation identification of unreported and reported mutation profile in exon 7 of N-Acetylgalactosamine-6-Sulfates (GALNS) gene of mucopolysaccharidosis type IV A (MPS IVA) patients in Indonesia

Abstract Mucopolysaccharidosis type IVA (MPS IVA), is an autosomal recessive genetic disorder because of N-acetylgalactosamine-6-sulfate deficiency which causes keratan sulfate and chondroitin sulfate to not degrade in lysosome. MPS IVA was caused of GALNS gene which located in chromosome 16q24.3 with the most frequent mutation occurrence in exon 7. There are no report or publication about MPS IVA or GALNS gene mutation in Indonesia, therefore this research is aimed to analyze the mutation profile in exon 7 of the GALNS gene in MPS IVA patients in Indonesia. The DNA from blood samples of four patients and three control samples from RSUPN Cipto Mangunkusumo were analyzed. Amplification by polymerase chain reaction was done after designing the primer. Furthermore, electrophoresis and sequencing analysis has been performed. The result shows that there is silent mutation c.708C&gt;T and nonsense mutation c.751C&gt;T. The silent mutation is categorized as a benign variant, while the nonsense mutation is categorized as a pathogenic variant because it may affect protein features and cause neuromuscular disorder. The silent and nonsense mutation that were found were already reported by Laradi and Morrone, but has not been reported in Indonesia. Further experiment was needed to find other mutation in other genes.</jats:p

Isolated and contiguous glycerol kinase gene disorders: a review

Glycerol kinase deficiency (GKD) is an X-linked recessive disorder. There are two types. an isolated form and a complex form. We review the clinical, biochemical and molecular genetic features of GKD. The clinical and biochemical phenotype of isolated GKD may vary from a life-threatening childhood metabolic crisis to asymptomatic adult 'pseudohypertriglyceridaemia', resulting from hyperglycerolaemia. To date 38 patients from 24 families with isolated GKD have been reported. At least 7 of these patients had a metabolic crisis during a catabolic condition. The complex GKD is an Xp21 contiguous gene syndrome involving the glycerol kinase locus together with the adrenal hypoplasia congenita (AHC) or Duchenne muscular dystrophy (DMD) loci or both. Clinical features of a patient with complex GKD depend on the loci that are involved. Approximately 100 patients from 78 families with a complex GKD have been reported. Seventeen patients with complex GKD (AHC-GKD-DMD or AHC-GKD) died in the neonatal period or early childhood because of unrecognized or inappropriate management of adrenal dysfunction. Since the outcome of the crisis in GKD is highly dependent on the physicians' knowledge of the disease, we devised an algorithmic approach to the diagnosis. From molecular genetic investigations of isolated GKD, 7 missense mutations, 2 splice site mutations, I nonsense mutation, 1 Alu Sx insertion and 2 small deletions were reported for isolated GKD in 13 unrelated families. In 4 families consisting of more than one patient with the same biochemical and genetic defect, the phenotypic variability of the isolated GKD was remarkable. The clinical variability in isolated GKD cannot be explained by biochemical or by molecular heterogeneity. Isolated GKD patients showed a tendency towards hypoglycaemia with hyperketonaemia; whether the clinical symptoms of GKD are caused by dysfunction of gluconeogenesis and/or ketolysis needs to be investigated furthe