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Fulltext Cucurbit[n]uril-Based Microcapsules Self-Assembled within Microfluidic Droplets: A Versatile Approach for Supramolecular Architectures and Materials

Liu J, Lan Y, Yu Z, Tan CS, Parker RM, Abell C, et al.

Acc Chem Res, 2017 Feb 21;50(2):208-217.
PMID: 28075551 DOI: 10.1021/acs.accounts.6b00429

Microencapsulation is a fundamental concept behind a wide range of daily applications ranging from paints, adhesives, and pesticides to targeted drug delivery, transport of vaccines, and self-healing concretes. The beauty of microfluidics to generate microcapsules arises from the capability of fabricating monodisperse and micrometer-scale droplets, which can lead to microcapsules/particles with fine-tuned control over size, shape, and hierarchical structure, as well as high reproducibility, efficient material usage, and high-throughput manipulation. The introduction of supramolecular chemistry, such as host-guest interactions, endows the resultant microcapsules with stimuli-responsiveness and self-adjusting capabilities, and facilitates hierarchical microstructures with tunable stability and porosity, leading to the maturity of current microencapsulation industry. Supramolecular architectures and materials have attracted immense attention over the past decade, as they open the possibility to obtain a large variety of aesthetically pleasing structures, with myriad applications in biomedicine, energy, sensing, catalysis, and biomimicry, on account of the inherent reversible and adaptive nature of supramolecular interactions. As a subset of supramolecular interactions, host-guest molecular recognition involves the formation of inclusion complexes between two or more moieties, with specific three-dimensional structures and spatial arrangements, in a highly controllable and cooperative manner. Such highly selective, strong yet dynamic interactions could be exploited as an alternative methodology for programmable and controllable engineering of supramolecular architectures and materials, exploiting reversible interactions between complementary components. Through the engineering of molecular structures, assemblies can be readily functionalized based on host-guest interactions, with desirable physicochemical characteristics. In this Account, we summarize the current state of development in the field of monodisperse supramolecular microcapsules, fabricated through the integration of traditional microfluidic techniques and interfacial host-guest chemistry, specifically cucurbit[n]uril (CB[n])-mediated host-guest interactions. Three different strategies, colloidal particle-driven assembly, interfacial condensation-driven assembly and electrostatic interaction-driven assembly, are classified and discussed in detail, presenting the methodology involved in each microcapsule formation process. We highlight the state-of-the-art in design and control over structural complexity with desirable functionality, as well as promising applications, such as cargo delivery stemming from the assembled microcapsules. On account of its dynamic nature, the CB[n]-mediated host-guest complexation has demonstrated efficient response toward various external stimuli such as UV light, pH change, redox chemistry, and competitive guests. Herein, we also demonstrate different microcapsule modalities, which are engineered with CB[n] host-guest chemistry and also can be disrupted with the aid of external stimuli, for triggered release of payloads. In addition to the overview of recent achievements and current limitations of these microcapsules, we finally summarize several perspectives on tunable cargo loading and triggered release, directions, and challenges for this technology, as well as possible strategies for further improvement, which will lead to substainitial progress of host-guest chemistry in supramolecular architectures and materials.
Fulltext Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia

Hamdan NE, Ng YL, Lee WB, Tan CS, Khan FA, Chong YL

Trop Life Sci Res, 2017 Jan;28(1):151-159.
PMID: 28228923 MyJurnal DOI: 10.21315/tlsr2017.28.1.11

Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential (n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) (p < 0.001 of Zar-t test based on the Shannon index). Rattus rattus and Sundamys muelleri were present at high frequencies in both localities. An enzyme-linked immunosorbent assay (ELISA) showed that hantavirus-targeting antibodies were absent from 53 tested serum samples. This is the first report of hantavirus seroprevalence surveillance in rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.
Activated ADI pathway: the initiator of intermediate vancomycin resistance in Staphylococcus aureus

Tan XE, Neoh HM, Looi ML, Chin SF, Cui L, Hiramatsu K, et al.

Can J Microbiol, 2017 Mar;63(3):260-264.
PMID: 28059579 DOI: 10.1139/cjm-2016-0439

Comparative proteomic profiling between 2 vancomycin-intermediate Staphylococcus aureus (VISA) strains, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm, and vancomycin-susceptible S. aureus (VSSA) strain Mu50Ω revealed upregulated levels of catabolic ornithine carbamoyltransferase (ArcB) of the arginine catabolism pathway in VISA strains. Subsequent analyses showed that the VISA strains have higher levels of cellular ATP and ammonia, which are by-products of arginine catabolism, and displayed thicker cell walls. We postulate that elevated cytoplasmic ammonia and ATP molecules, resulting from activated arginine catabolism upon acquisition of vraS and graR mutations, are important requirements facilitating cell wall biosynthesis, thereby contributing to thickened cell wall and consequently reduced vancomycin susceptibility in VISA strains.
Tough Supramolecular Polymer Networks with Extreme Stretchability and Fast Room-Temperature Self-Healing

Liu J, Tan CSY, Yu Z, Li N, Abell C, Scherman OA

Adv Mater, 2017 Jun;29(22).
PMID: 28370560 DOI: 10.1002/adma.201605325

Recent progress on highly tough and stretchable polymer networks has highlighted the potential of wearable electronic devices and structural biomaterials such as cartilage. For some given applications, a combination of desirable mechanical properties including stiffness, strength, toughness, damping, fatigue resistance, and self-healing ability is required. However, integrating such a rigorous set of requirements imposes substantial complexity and difficulty in the design and fabrication of these polymer networks, and has rarely been realized. Here, we describe the construction of supramolecular polymer networks through an in situ copolymerization of acrylamide and functional monomers, which are dynamically complexed with the host molecule cucurbit[8]uril (CB[8]). High molecular weight, thus sufficient chain entanglement, combined with a small-amount dynamic CB[8]-mediated non-covalent crosslinking (2.5 mol%), yields extremely stretchable and tough supramolecular polymer networks, exhibiting remarkable self-healing capability at room temperature. These supramolecular polymer networks can be stretched more than 100× their original length and are able to lift objects 2000× their weight. The reversible association/dissociation of the host-guest complexes bestows the networks with remarkable energy dissipation capability, but also facile complete self-healing at room temperature. In addition to their outstanding mechanical properties, the networks are ionically conductive and transparent. The CB[8]-based supramolecular networks are synthetically accessible in large scale and exhibit outstanding mechanical properties. They could readily lead to the promising use as wearable and self-healable electronic devices, sensors and structural biomaterials.
Fulltext Endophytic Diaporthe sp. ED2 Produces a Novel Anti-Candidal Ketone Derivative

Tong WY, Leong CR, Tan WN, Khairuddean M, Zakaria L, Ibrahim D

J Microbiol Biotechnol, 2017 Jun 28;27(6):1065-1070.
PMID: 28297749 DOI: 10.4014/jmb.1612.12009

This study aimed to examine the anti-candidal efficacy of a novel ketone derivative isolated from Diaporthe sp. ED2, an endophytic fungus residing in medicinal herb Orthosiphon stamieus Benth. The ethyl acetate extract of the fungal culture was separated by open column and reverse phase high-performance liquid chromatography (HPLC). The eluent at retention time 5.64 min in the HPLC system was the only compound that exhibited anti-candidal activity on Kirby-Bauer assay. The structure of the compound was also elucidated by nuclear magnetic resonance and spectroscopy techniques. The purified anti-candidal compound was obtainedas a colorless solid and characterized as 3-hydroxy-5-methoxyhex-5-ene-2,4-dione. On broth microdilution assay, the compound also exhibited fungicidal activity on a clinical strain of Candida albicans at a minimal inhibitory concentration of 3.1 μg/ml. The killing kinetic analysis also revealed that the compound was fungicidal against C. albicans in a concentration- and time-dependent manner. The compound was heat-stable up to 70°C, but its anti-candidal activity was affected at pH 2.
Vasodilatory Effects of Combined Traditional Chinese Medicinal Herbs in Optimized Ratio

Loh YC, Tan CS, Ch'ng YS, Ahmad M, Asmawi MZ, Yam MF

J Med Food, 2017 Mar;20(3):265-278.
PMID: 28296594 DOI: 10.1089/jmf.2016.3836

Recently, a new syndromic disease combination theory of traditional Chinese medicine (TCM) for hypertensive treatment has been introduced. In the wake of this new concept, a new science-based TCM formula that counteracts various syndromes is needed. The objective of this study was to develop such a formula. Five of the most clinically prescribed TCM herbs that work on different syndromes, namely Gastrodia elata, Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale, were selected for this study. The fingerprints of these five herbs were analyzed by tri-step Fourier transform infrared spectroscopy. Three different solvents, 95% ethanol, 50% ethanol, and distilled water, were used for the maceration of the herbs and their vasodilatory effects were studied using in vitro precontracted aortic ring model. Among these, the 50% ethanolic extracts of G. elata (GE50) and A. orientale (AO50), and 95% ethanolic extracts of U. rhynchophylla (UR95), P. thomsonii (PT95), and P. notoginseng (PN95) were found to be the most effective for eliciting vasodilation. Thus, these five extracts were used for orthogonal stimulus-response compatibility group studies by using L25 (5(5)) formula. The best combination ratio for GE50, UR95, PT95, PN95, and AO50, which was assigned as Formula 1 (F1), was found at EC0, EC25, EC20, EC20, and EC10, respectively. The vasodilatory effect of the extracts prepared from different extraction methods using F1 ratio was also studied. From the results, the EC50 and Rmax of total 50% ethanolic extract of five herbs using F1 ratio (F1-2) were 0.028 ± 0.005 mg/mL and 101.71% ± 3.64%, with better values than F1 (0.104 ± 0.014 mg/mL and 97.80% ± 3.12%, respectively). In conclusion, the optimum ratio and appropriate extraction method (F1-2) for the new TCM formula were revealed.
Identification of Optimal Reference Genes for Normalization of RT-qPCR Data in Cancerous and Non-Cancerous Tissues of Human Uterine Cervix

Tan SC, Ismail MP, Duski DR, Othman NH, Bhavaraju VM, Ankathil R

Cancer Invest, 2017 Mar 16;35(3):163-173.
PMID: 28301252 DOI: 10.1080/07357907.2017.1278767

This study aimed to identify the most stably expressed reference genes from a panel of 32 candidate genes for normalization of reverse transcription-quantitative real-time polymerase chain reaction data in cancerous and non-cancerous tissues of human uterine cervix. Overall, PUM1, YWHAZ, and RPLP0 were identified as the most stably expressed genes in paired cancerous and non-cancerous tissues. The results were further stratified by the state of malignancy of the tissues, histopathological type of the cancer, and the human papillomavirus-type.
FAS c.-671A>G polymorphism and cervical cancer risk: a case-control study and meta-analysis

Tan SC, Ismail MP, Duski DR, Othman NH, Ankathil R

Cancer Genet, 2017 02;211:18-25.
PMID: 28279307 DOI: 10.1016/j.cancergen.2017.01.004

This study aimed to investigate the association between FAS c.-671A>G polymorphism and cervical cancer risk in a case-control setting, followed by a meta-analysis of the published literatures. The case-control study involved genotyping of the polymorphism in 185 histopathologically confirmed cervical cancer patients and 209 cancer-free female controls utilizing PCR-RFLP technique, followed by logistic regression analyses. Meta-analysis was then conducted under homozygous, heterozygous, dominant, recessive and allele contrast models to combine data from 12 studies which consisted of 2798 cases and 3039 controls. Our case-control analysis revealed a significant association of the variant allele (G) and the homozygous variant genotype (GG) of the FAS polymorphism with an increased risk of cervical cancer. Subgroup analysis by ethnicity further confirmed the risk association in Malays (P 0.05). However, results of meta-analysis suggested a lack of association between the polymorphism and cervical cancer risk in all the five genetic models analyzed. In conclusion, while the FAS c.-671A>G polymorphism may serve as a biomarker for cervical cancer risk prediction among the Malays, there is a limited usability of the polymorphism as a cervical cancer risk biomarker in other populations.
Biomimetic Supramolecular Polymer Networks Exhibiting both Toughness and Self-Recovery

Liu J, Tan CS, Yu Z, Lan Y, Abell C, Scherman OA

Adv Mater, 2017 Mar;29(10).
PMID: 28092128 DOI: 10.1002/adma.201604951

Biomimetic supramolecular dual networks: By mimicking the structure/function model of titin, integration of dynamic cucurbit[8]uril mediated host-guest interactions with a trace amount of covalent cross-linking leads to hierarchical dual networks with intriguing toughness, strength, elasticity, and energy dissipation properties. Dynamic host-guest interactions can be dissociated as sacrificial bonds and their facile reformation results in self-recovery of the dual network structure as well as its mechanical properties.
Biodiesel Production from Citrillus colocynthis Oil Using Enzymatic Based Catalytic Reaction and Characterization Studies

Nehdi IA, Sbihi HM, Blidi LE, Rashid U, Tan CP, Al-Resayes SI

Protein Pept Lett, 2018;25(2):164-170.
PMID: 28240158 DOI: 10.2174/0929866524666170223150839

BACKGROUND: Biodiesel is a green fuel consisting of long chain fatty acid monoalkyl esters, which can be blended with diesel or used alone which is usually produced from vegetable oils/fats by either lipasecatalyzed transesterification. In this investigation, an enzyme (Novozym 435) catalyzed process was optimized to prepare methyl esters from crude Citrullus colocynthis oil (CCO) by transesterification of CCO with methanol. However, as per our knowledge, lipase-catalyzed transesterification have not been used for biodiesel production from Citrullus colocynthis.
OBJECTIVE: The purpose of this work was to transesterify the CCO in the presence of Candida antarctica lipase as catalyst and methanol. Additionally, the physicochemical parameters/fuel properties of the Citrullus colocynthis methyl ester (CCME) were assessed and compared.
METHODS: Lipase-catalyzed reactions were carried out in three necked flask (50 mL) attached with reflux condenser and thermometer, immersed in oil bath at constant stirring speed (400 rpm). The reaction mixture was consisted of CCO and varying the calculated amount of methanol, tert-butyl alcohol, and Novozym 435. The experimental parameters reaction time, methanol/oil molar ratio, reaction temperature, tert-butanol content, Novozym 435 content and water content were optimized for the transesterification reaction. The CCME yield was measured using gas chromatograph. The fuel properties of the produced CCME were determined as per American Society for Testing and Materials (ASTM) and European (EN) biodiesel standard methods.
RESULTS: In this study, an enzymatic catalyst was employed to synthesize the CCME from CCO via transesterification. Several variables affecting the CCME yield were optimized as lipase quantity (4%), water content (0.5%), methanol/oil molar ratio (5:1), reaction temperature (43 °C), reaction medium composition (80% tertbutanol/ oil), and reaction time (3.7 h). A CCME yield of 97.8% was achieved using enzyme catalyzed transesterification of CCO under optimal conditions. The significant biodiesel fuel properties of CCME, i.e. cloud point (0.70 °C); cetane number (49.07); kinematic viscosity (2.27 mm2/s); flash point (143 °C); sulfur content (2 ppm) density (880 kg/m3) and acid value (0.076 mg KOH/g) were appraised. CCME also exhibited long-term storage stability (4.80 h) and all the biodiesel fuel properties were within the range of standards (ASTM D6751 and EN 14214).
CONCLUSION: The lipase-catalyzed transesterification produced better conversion than the base-catalyzed reaction. The fuel properties of CCME were within the limits of the ASTM D6751 and EN14214 standards. Furthermore, CCME showed good oxidative stability and a long shelf life due its high natural antioxidant content. CCME showed better fuel properties and long-term storage stability due to which it can be used as a potential alternative fuel.
Fulltext Digging deeper: new gene order rearrangements and distinct patterns of codons usage in mitochondrial genomes among shrimps from the Axiidea, Gebiidea and Caridea (Crustacea: Decapoda)

Tan MH, Gan HM, Lee YP, Poore GC, Austin CM

PeerJ, 2017;5:e2982.
PMID: 28265498 DOI: 10.7717/peerj.2982

BACKGROUND: Whole mitochondrial DNA is being increasingly utilized for comparative genomic and phylogenetic studies at deep and shallow evolutionary levels for a range of taxonomic groups. Although mitogenome sequences are deposited at an increasing rate into public databases, their taxonomic representation is unequal across major taxonomic groups. In the case of decapod crustaceans, several infraorders, including Axiidea (ghost shrimps, sponge shrimps, and mud lobsters) and Caridea (true shrimps) are still under-represented, limiting comprehensive phylogenetic studies that utilize mitogenomic information.
METHODS: Sequence reads from partial genome scans were generated using the Illumina MiSeq platform and mitogenome sequences were assembled from these low coverage reads. In addition to examining phylogenetic relationships within the three infraorders, Axiidea, Gebiidea, and Caridea, we also investigated the diversity and frequency of codon usage bias and mitogenome gene order rearrangements.
RESULTS: We present new mitogenome sequences for five shrimp species from Australia that includes two ghost shrimps, Callianassa ceramica and Trypaea australiensis, along with three caridean shrimps, Macrobrachium bullatum, Alpheus lobidens, and Caridina cf. nilotica. Strong differences in codon usage were discovered among the three infraorders and significant gene order rearrangements were observed. While the gene order rearrangements are congruent with the inferred phylogenetic relationships and consistent with taxonomic classification, they are unevenly distributed within and among the three infraorders.
DISCUSSION: Our findings suggest potential for mitogenome rearrangements to be useful phylogenetic markers for decapod crustaceans and at the same time raise important questions concerning the drivers of mitogenome evolution in different decapod crustacean lineages.
Ethyl nitrobenzoate: A novel scaffold for cholinesterase inhibition

Yeong KY, Liew WL, Murugaiyah V, Ang CW, Osman H, Tan SC

Bioorg Chem, 2017 02;70:27-33.
PMID: 27863748 DOI: 10.1016/j.bioorg.2016.11.005

A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease.
Two-dimensional bismuth oxybromide coupled with molybdenum disulphide for enhanced dye degradation using low power energy-saving light bulb

Lee WPC, Wong FH, Attenborough NK, Kong XY, Tan LL, Sumathi S, et al.

J Environ Manage, 2017 Jul 15;197:63-69.
PMID: 28324782 DOI: 10.1016/j.jenvman.2017.03.027

In the present work, two-dimensional bismuth oxybromide (BiOBr) was synthesized and coupled with co-catalyst molybdenum disulphide (MoS2) via a simple hydrothermal process. The photoactivity of the resulting hybrid photocatalyst (MoS2/BiOBr) was evaluated under the irradiation of 15 W energy-saving light bulb at ambient condition using Reactive Black 5 (RB5) as model dye solution. The photo-degradation of RB5 by BiOBr loaded with 0.2 wt% MoS2 (MoBi-2) exhibited more than 1.4 and 5.0 folds of enhancement over pristine BiOBr and titanium dioxide (Degussa, P25), respectively. The increased photocatalytic performance was a result of an efficient migration of excited electrons from BiOBr to MoS2, prolonging the electron-hole pairs recombination rate. A possible charge transfer diagram of this hybrid composite photocatalyst, and the reaction mechanism for the photodegradation of RB5 were proposed.
Sensitivity enhancement of graphene/zinc oxide nanocomposite-based electrochemical impedance genosensor for single stranded RNA detection

Low SS, Loh HS, Boey JS, Khiew PS, Chiu WS, Tan MTT

Biosens Bioelectron, 2017 Aug 15;94:365-373.
PMID: 28319904 DOI: 10.1016/j.bios.2017.02.038

An efficient electrochemical impedance genosensing platform has been constructed based on graphene/zinc oxide nanocomposite produced via a facile and green approach. Highly pristine graphene was synthesised from graphite through liquid phase sonication and then mixed with zinc acetate hexahydrate for the synthesis of graphene/zinc oxide nanocomposite by solvothermal growth. The as-synthesised graphene/zinc oxide nanocomposite was characterised with scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy and X-ray diffractometry (XRD) to evaluate its morphology, crystallinity, composition and purity. An amino-modified single stranded DNA oligonucleotide probe synthesised based on complementary Coconut Cadang-Cadang Viroid (CCCVd) RNA sequence, was covalently bonded onto the surface of graphene/zinc oxide nanocomposite by the bio-linker 1-pyrenebutyric acid N-hydroxysuccinimide ester. The hybridisation events were monitored by electrochemical impedance spectroscopy (EIS). Under optimised sensing conditions, the single stranded CCCVd RNA oligonucleotide target could be quantified in a wide range of 1.0×10-11M to 1.0×10-6 with good linearity (R =0.9927), high sensitivity with low detection limit of 4.3×10-12M. Differential pulse voltammetry (DPV) was also performed for the estimation of nucleic acid density on the graphene/zinc oxide nanocomposite-modified sensing platform. The current work demonstrates an important advancement towards the development of a sensitive detection assay for various diseases involving RNA agents such as CCCVd in the future.
Age estimation from structural changes of teeth and buccal alveolar bone level

Koh KK, Tan JS, Nambiar P, Ibrahim N, Mutalik S, Khan Asif M

J Forensic Leg Med, 2017 May;48:15-21.
PMID: 28407514 DOI: 10.1016/j.jflm.2017.03.004

Forensic odontology plays a vital role in the identification and age estimation of unknown deceased individuals. The purpose of this study is to estimate the chronological age from Cone-Beam Computed Tomography (CBCT) images by measuring the buccal alveolar bone level (ABL) to the cemento-enamel junction and to investigate the possibility of employing the age-related structural changes of teeth as studied by Gustafson. In addition, this study will determine the forensic reliability of employing CBCT images as a technique for dental age estimation. A total of 284 CBCT images of Malays and Chinese patients (150 females and 134 males), aged from 20 years and above were selected, measured and stages of age-related changes were recorded using the i-CAT Vision software. Lower first premolars of both left and right side of the jaw were chosen and the characteristics described by Gustafson, namely attrition, secondary dentine formation and periodontal recession were evaluated. Linear regression analysis was performed for the buccal bone level and the R values obtained were 0.85 and 0.82 for left and right side respectively. Gustafson's characteristics were analysed using multiple regression analysis with chronological age as the dependent variable. The results of the analysis showed R values ranged from 0.44 to 0.62. Therefore it can be safely concluded that the buccal bone level highly correlated with the chronological age and is consequently the most suitable age-related characteristic for forensic age estimation.
Fulltext Pernicious anaemia among Asians in Singapore

Jayaratnam FJ, Seah CS, Da Costa JL, Tan KK, O'Brien W

Br Med J, 1967 Jul 01;3(5556):18-20.
PMID: 6027375
Fulltext Carbimazole-induced aplastic anaemia - a case report

Vijay AP, Lim SS, Tan ATB, Rokiah P, Chan SP

JUMMEC, 2009;12(2):92-95.
MyJurnal

Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well, but some may develop rare life threatening side effects such as agranulocytosis and aplastic anaemia. Clinical experience with the latter condition is extremely limited. We report on a case of carbimazole-induced aplastic anaemia caused by hypocellular bone marrow and associated plasmacytosis in a thyrotoxic patient chronically treated with carbimazole. This resolved after substitution with propylthiouracil. The clinical course was complicated by neutropaenic septicaemia and atrial fibrillation.
Study site: University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Fulltext Cold allodynia as the presenting symptom in a case of acquired neuromyotonia (Isaacs syndrome) with multiple autoantibodies

Goh KJ, Abdullah S, Wong WF, Yeap SS, Shahrizaila N, Tan CT

Neurology Asia, 2014;19(4):409-412.
MyJurnal

We report a patient who presented with severe cold-induced allodynia and hyperhidrosis, and found to have acquired neuromyotonia (Isaacs syndrome) with high voltage-gated potassium channel (VGKC) antibody titre,positive contactin-associated protein 2 (CASPR2) and leucine-rich glioma-inactivated 1 (LGI1) antibodies. The patient also had positive anti-dsDNA and acetylcholine receptor (AChR) antibodies without clinical features of SLE or myasthenia gravis, suggesting a strong underlying autoimmune tendency. CT thorax showed no thymoma. Her symptoms improved with intravenous immunoglobulin infusion but recurred despite maintenance oral corticosteroids and carbamazepine. She has since been on regular IVIG infusions. Cold allodynia is an unusual presentation in acquired neuromyotonia.
Fulltext Neonatal conjunctivitis: a review

Mallika P.S., Asokumaran T, Faisal H. A., Aziz S, Tan A. K., Intan G

Malays Fam Physician, 2008;3(2):77-81.
MyJurnal

Ophthalmia neonatorum remains a significant cause of ocular morbidity, blindness and even death in underdeveloped countries. The organisms causing ophthalmia neonatorum are acquired mainly from the mother's birth canal during delivery and a small percentage of cases are acquired by other ways. Chlamydia and Neisseria are the most common pathogens responsible for the perinatal infection. Fortunately in most cases, laboratory studies can identify the causative organism and unlike other form of conjunctivitis, this perinatal ocular infection has to be treated with systemic antibiotics to prevent systemic colonization of the organism. Routine prophylaxis with 1% silver nitrate solution (credes method) has been discontinued in many developed nations for the fear of development of chemical conjunctivitis.
Fulltext Thyroid associated ophthalmopathy - a review

Mallika PS, Tan AK, Aziz S, Syed Alwi SAR, Chong MS, Vanitha R, et al.

Malays Fam Physician, 2009;4(1):8-14.
PMID: 25606151 MyJurnal

Thyroid associated ophthalmopathy is an autoimmune disorder affecting the orbital and periorbital tissues. Hyperthyroidism is commonly associated with thyroid associated ophthalmopathy, however in 5% to 10% of cases it is euthyroid. Genetic, environmental and endogenous factors play a role in the initiation of the thyroid ophthalmopathy. Smoking has been identified as the strongest risk factor for the development of the disorder. The pathogenesis involves activation of both humoral and cell mediated immunity with subsequent production of gycoaminoglycans, hyaluronic acid resulting in oedema formation, increase extraocular mass and adipogenesis in the orbit. The natural history of the disease progresses from active to inactive fibrotic stage over a period of years. Diagnosis is mainly clinical and almost all patients with ophthalmopathy exhibit some form of thyroid abnormality on further testing. Treatment is based on the clinical severity of the disease. Non-severe cases are managed by supportive measures to reduce the symptomatology and severe cases are treated by either medical or surgical decompression. Rehabilitative surgery is done for quiescent disease to reduce diplopia and improve cosmesis.

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