1.Single mitochondrial DNA deletions in chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) patients from a multiethnic Asian population
Jia-Woei Chong ; Azlina Ahmad Annuar ; Kum-Thong Wong ; Meow-Keong Thong ; Khean-Jin Goh
Neurology Asia 2014;19(1):27-36
Mitochondrial DNA (mtDNA) deletions are a major cause of chronic progressive external ophthalmoplegia
(CPEO) and Kearns-Sayre syndrome (KSS). We analyzed single mtDNA deletions in 11 CPEO and
one KSS patients by means of Southern blot and long polymerase chain reaction (PCR) assays. The
deletion sizes ranged from 3.4 kb to 6.9 kb whereas the heteroplasmy level varied from 18.8% to
85.5%. Two unique deletions sized 4320 bp and 4717 bp were found. This study represents the first
genetic screen of mtDNA disorders in Malaysia, and it follows the data seen in other published reports
on CPEO and KSS genetic aetiology.
2.The frequency of common mitochondrial DNA mutations in a cohort of Malaysian patients with specifi c mitochondrial encephalomyopathy syndromes
Jia-Woei Chong ; Azlina Ahmad Annuar ; Kum-Thong Wong ; MeowKeong Thong ; Khean-Jin Goh
Neurology Asia 2011;16(4):321-327
A cohort of Malaysian patients with clinico-pathological diagnosis of three specifi c mitochondrial
encephalomyopathy syndromes comprising of mitochondrial encephalomyopathy, lactic acidosis
and stroke-like episodes (MELAS), myoclonus epilepsy with ragged-red fi bers (MERRF) and Leigh
syndrome were studied to determine the frequency of their common mitochondrial DNA mutations. The
‘hot-spot’ point mutations for MELAS, MERRF and Leigh syndrome were screened. In the absence
of common point mutations, screening of large-scale deletions as well as sequencing of tRNALeu and
tRNALys genes were performed. Of 22 patients studied, nine m.3243A>G mutations, four m.8344A>G
mutations, one m.8993T>G mutation and one deletion were identifi ed (65% detection rate). While the
m.3243A>G mutation was closely associated with MELAS, the m.8344A>G was more heterogenous,
being seen in one MERFF, two isolated mitochondrial myopathies and one Leigh syndrome patient.
Screening for m.8993T>G in Leigh syndrome has a low yield as unsurprisingly Leigh syndrome has
considerable genetic heterogeneity.
3.Bioequivalence and pharmacokinetic comparison of two fixed dose combination of Metformin/Glibenclamide formulations in healthy subjects under fed condition
Chang Chee Tao ; Ang Ju Ying ; Wong Jia Woei ; Tan Siew Siew ; Chin Siaw Kuen ; Lim Ai Beoy ; Tan Weng Hong ; Yuen Kah Hay
The Medical Journal of Malaysia 2020;75(3):286-291
Aim: This study is conducted to compare the
pharmacokinetic profiles of two fixed dose combination of
metformin/glibenclamide tablets (500mg/5 mg per tablet).
Materials and Methods: This is a single-center, single-dose,
open-label, randomized, 2-treatment, 2-sequence and 2-
period crossover study with a washout period of 7 days. All
28 adult male subjects were required to fast for at least 10
hours prior to drug administration and they were given
access to water ad libitum during this period. Thirty minutes
prior to dosing, all subjects were served with a standardized
high-fat and high-calorie breakfast with a total calorie of
1000 kcal which was in accordance to the EMA Guideline on
the Investigation of Bioequivalence. Subsequently, subjects
were administered either the test or reference preparation
with 240mL of plain water in the first trial period. During the
second trial period, they received the alternate preparation.
Plasma levels of glibenclamide and metformin were
analysed separately using two different high performance
liquid chromatography methods.
Results: The 90% confidence interval (CI) for the ratio of the
AUC0-t, AUC0-∞, and Cmax of the test preparation over
those of the reference preparation were 0.9693–1.0739,
0.9598– 1.0561 and 0.9220 – 1.0642 respectively. Throughout
the study period, no serious drug reaction was observed.
However, a total of 26 adverse events (AE)/side effects were
reported, including 24 that were definitely related to the
study drugs, namely giddiness (n=17), while diarrheoa (n=3),
headache (n=2) and excessive hunger (n=2) were less
commonly reported by the subjects.
Conclusion: It can be concluded that the test preparation is
bioequivalent to the reference preparation.