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Acetic acid induces pH-independent cellular energy depletion in Salmonella enterica

Tan SM, Lee SM, Dykes GA

Foodborne Pathog Dis, 2015 Mar;12(3):183-9.
PMID: 25562466 DOI: 10.1089/fpd.2014.1853

Weak organic acids are widely used as preservatives and disinfectants in the food industry. Despite their widespread use, the antimicrobial mode of action of organic acids is still not fully understood. This study investigated the effect of acetic acid on the cell membranes and cellular energy generation of four Salmonella strains. Using a nucleic acid/protein assay, it was established that acetic acid did not cause leakage of intracellular components from the strains. A scanning electron microscopy study further confirmed that membrane disruption was not the antimicrobial mode of action of acetic acid. Some elongated Salmonella cells observed in the micrographs indicated a possibility that acetic acid may inhibit DNA synthesis in the bacterial cells. Using an ATP assay, it was found that at a neutral pH, acetic acid caused cellular energy depletion with an ADP/ATP ratio in the range between 0.48 and 2.63 (p<0.05) that was apparent for the four Salmonella strains. We suggest that this effect was probably due solely to the action of undissociated acid molecules. The antimicrobial effect of acetic acid was better under acidic conditions (ADP/ATP ratio of 5.56 ± 1.27; p<0.05), where the role of both pH and undissociated acid molecules can act together. We concluded that the inhibitory effect of acetic acid is not solely attributable to acidic pH but also to undissociated acid molecules. This finding has implication for the use of acetic acid as an antimicrobial against Salmonella on food products, such as chicken meat, which can buffer its pH.
A comparative study of physicochemical characteristics and functionalities of pinto bean protein isolate (PBPI) against the soybean protein isolate (SPI) after the extraction optimisation

Tan ES, Ying-Yuan N, Gan CY

Food Chem, 2014;152:447-55.
PMID: 24444960 DOI: 10.1016/j.foodchem.2013.12.008

Optimisation of protein extraction yield from pinto bean was investigated using response surface methodology. The maximum protein yield of 54.8 mg/g was obtained with the optimal conditions of: temperature=25 °C, time=1 h and buffer-to-sample ratio=20 ml/g. PBPI was found to obtain high amount of essential amino acids such as leucine, lysine, and phenylalanine compared to SPI. The predominant proteins of PBPI were vicilin and phytohemagglutinins whereas the predominant proteins of SPI were glycinin and conglycinins. Significantly higher emulsifying capacity was found in PBPI (84.8%) compared to SPI (61.9%). Different isoelectric points were found in both PBPI (4.0-5.5) and SPI (4.0-5.0). Also, it was found that PBPI obtained a much higher denaturation temperature of 110.2 °C compared to SPI (92.5 °C). Other properties such as structural information, gelling capacity, water- and oil-holding capacities, emulsion stability as well as digestibility were also reported.
Pulmonary manifestation as initial presentation for systemic lupus erythematosus

Khor CG, Kan SL, Tan BE

Int J Rheum Dis, 2018 Jun;21(6):1322-1325.
PMID: 24495523 DOI: 10.1111/1756-185X.12302

We report a 29-year-old Malay man who had pulmonary manifestations as an initial presentation for systemic lupus erythematosus. He had prolonged hospitalization and was treated with intensive care therapy with immunosuppressants.
In vitro differentiation of mesenchymal stem cells into mesangial cells when co-cultured with injured mesangial cells

Wong CY, Tan EL, Cheong SK

Cell Biol Int, 2014 Apr;38(4):497-501.
PMID: 24375917 DOI: 10.1002/cbin.10231

Mesangial cells are one of the three major cell types of the kidney glomerulus that provide physical support for the glomerular capillary lumen of the kidney. Loss of mesangial cells due to pathologic conditions, such as glomerulonephritis and diabetic nephropathy, can impair renal function. Mesenchymal stem cells (MSC) are attractive candidates for kidney repair therapy since they can enhance recovery and protect against kidney failure. MSC can differentiate into mesangial cells in vivo. We have investigated the ability of MSC to differentiate into mesangial cells in vitro; they were co-cultured with oxidant-injured mesangial cells before being analysed by flow cytometry and for contractility. MSC co-cultured with injured mesangial cells had a mesangial cell-like morphology and contracted in response to angiotensin II. They expressed CD54(-) CD62E(+) in direct contrast to the CD54(+) CD62E(-) of pure MSC. In conclusion, MSC can differentiate into mesangial cells in vitro when co-cultured with injured mesangial cells.
Attachment of bacterial pathogens to a bacterial cellulose-derived plant cell wall model: a proof of concept

Tan MS, Wang Y, Dykes GA

Foodborne Pathog Dis, 2013 Nov;10(11):992-4.
PMID: 23941519 DOI: 10.1089/fpd.2013.1536

This study aimed to establish, as a proof of concept, whether bacterial cellulose (BC)-derived plant cell wall models could be used to investigate foodborne bacterial pathogen attachment. Attachment of two strains each of Salmonella enterica and Listeria monocytogenes to four BC-derived plant cell wall models (namely, BC, BC-pectin [BCP], BC-xyloglucan [BCX], and BC-pectin-xyloglucan [BCPX]) was investigated. Chemical analysis indicated that the BCPX composite (31% cellulose, 45.6% pectin, 23.4% xyloglucan) had a composition typical of plant cell walls. The Salmonella strains attached in significantly (p<0.05) higher numbers (~6 log colony-forming units [CFU]/cm(2)) to the composites than the Listeria strains (~5 log CFU/cm(2)). Strain-specific differences were also apparent with one Salmonella strain, for example, attaching in significantly (p<0.05) higher numbers to the BCX composite than to the other composites. This study highlights the potential usefulness of these composites to understand attachment of foodborne bacteria to fresh produce.
Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents

Rehman K, Tan CM, Zulfakar MH

Drug Res (Stuttg), 2014 Mar;64(3):159-65.
PMID: 24026957 DOI: 10.1055/s-0033-1355351

Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA) are one of the common treatments for inflammatory skin diseases. However, the amount of drug delivery through the skin is limited due to the stratum corneum. The purposes of this study were to investigate the ability of fish oil to act as penetration enhancer for topical keratolytic agents and to determine the suitable gelator for formulating stable fish oil oleogels. 2 types of gelling agents, beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and comparative analysis was performed using Franz diffusion cell. Stability of oleogels was determined by physical assessments at 20°C and 40°C storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were considered as better formulations in terms of drug permeation and cumulative drug release. All the results were found to be statistically significant (p<0.05, ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can prove to be beneficial in terms of permeation across the skin and stability.
Molecular delivery of plasmids for genetic vaccination

Mazid R, Tan MX, Danquah MK

Curr Pharm Biotechnol, 2013;14(6):615-22.
PMID: 24016267

Plasmid vaccination is a smart gene delivery application mostly achieved through the utilisation of viral or copolymeric systems as surrogated carriers in micro or nano formulations. A common polymeric protocol for plasmid vaccine formulation, which as somewhat been successful, is via the complexation of the DNA molecules with a cationic polymer, and encapsulating in a vehicular carrier polymer. Even though plasmid vaccination research has not witnessed the much anticipated success, due a number of cellular and physicochemical reasons, application of copolymeric carriers with tight functionalities is a promising strategy to optimally deliver the DNA molecules; in view of the available chemistries and physical properties that could be tuned to enable enhanced targeted delivery, uptake and specific transfection. This also enables the targeting of specific epitopes and antigen presenting cells for the treatment of many pathogenic infections and cancer. This paper provides a brief critical review of the current state of plasmid vaccines formulation and molecular delivery with analysis of performance data obtained from clinical trials.
Fulltext Influence of astaxanthin, emulsifier and organic phase concentration on physicochemical properties of astaxanthin nanodispersions

Anarjan N, Nehdi IA, Tan CP

Chem Cent J, 2013;7(1):127.
PMID: 23875816 DOI: 10.1186/1752-153X-7-127

The emulsification-evaporation method was used to prepare astaxanthin nanodispersions using a three-component emulsifier system composed of Tween 20, sodium caseinate and gum Arabic. Using Response-surface methodology (RSM), we studied the main and interaction effects of the major emulsion components, namely, astaxanthin concentration (0.02-0.38 wt %, x1), emulsifier concentration (0.2-3.8 wt %, x2) and organic phase (dichloromethane) concentration (2-38 wt %, x3) on nanodispersion characteristics. The physicochemical properties considered as response variables were: average particle size (Y1), PDI (Y2) and astaxanthin loss (Y3).
Display of the VP1 epitope of foot-and-mouth disease virus on bacteriophage T7 and its application in diagnosis

Wong CL, Sieo CC, Tan WS

J Virol Methods, 2013 Nov;193(2):611-9.
PMID: 23933075 DOI: 10.1016/j.jviromet.2013.07.053

Foot-and-mouth disease (FMD) is a highly contagious epidemic disease threatening the cattle industry since the sixteenth century. In recent years, the development of diagnostic assays for FMD has benefited considerably from the advances of recombinant DNA technology. In this study, the immunodominant region of the capsid protein VP1 of the foot-and-mouth disease virus (FMDV) was fused to the T7 bacteriophage and expressed on the surface of the bacteriophage capsid protein. The recombinant protein of about 42 kDa was detected by the anti-T7 tag monoclonal antibody in Western blot analysis. Phage ELISA showed that both the vaccinated and positive infected bovine sera reacted significantly with the recombinant T7 particle. This study demonstrated the potential of the T7 phage displaying the VP1 epitope as a diagnostic reagent.
Fulltext Vitamin D and its relationship with markers of bone metabolism in healthy Asian women

Tan KM, Saw S, Sethi SK

J Clin Lab Anal, 2013 Jul;27(4):301-4.
PMID: 23852789 DOI: 10.1002/jcla.21602

BACKGROUND: In this study, we aimed to determine the normal ranges of 25-hydroxy-vitamin D(3) (25-OHD(3)), parathyroid hormone (PTH), and the markers of bone turnover, procollagen type 1 N propeptide (P1NP) and C-terminal cross-linked telopeptide of type 1 collagen (CTX), in normal healthy women in Singapore, and to explore the relationship between vitamin D, PTH, and these markers of bone turnover in the women.
METHODS: One hundred and ninety-seven healthy women, aged 25 to 60, were selected from a hospital staff health screening program; 68% were Chinese, 18% Malay, and 14% Indian. P1NP, CTX, and 25-OHD(3) were measured using the Roche Cobas® electrochemiluminescence immunoassay. Serum PTH was measured using the Siemens ADVIA Centaur® immunoassay.
RESULTS: Sixty-five percent had 25-OHD(3) concentrations <50 nmol/l. Vitamin D insufficiency (25-OHD(3) < 50 nmol/l) was more prevalent in Malays (89%) and Indians (82%) compared to Chinese (56%). There was no correlation between vitamin D and age. PTH positively correlated with age, and Malays and Indians had higher PTH concentrations than Chinese. There was an inverse correlation between PTH and 25-OHD(3), but no threshold of 25-OHD(3) concentrations at which PTH plateaued. The bone turnover markers P1NP and CTX inversely correlated with age but were not different between ethnic groups. CTX and P1NP exhibited good correlation, however, there was no significant correlation between 25-OHD(3) or PTH concentrations and the bone turnover markers P1NP and CTX.
CONCLUSIONS: Healthy women in Singapore have a high prevalence of vitamin D insufficiency. Vitamin D insufficiency was more prevalent in Malays and Indians compared to Chinese.
Fulltext Comparative effects of plant growth regulators on leaf and stem explants of Labisia pumila var. alata

Ling AP, Tan KP, Hussein S

J Zhejiang Univ Sci B, 2013 Jul;14(7):621-31.
PMID: 23825148 DOI: 10.1631/jzus.B1200135

OBJECTIVE: Labisia pumila var. alata, commonly known as 'Kacip Fatimah' or 'Selusuh Fatimah' in Southeast Asia, is traditionally used by members of the Malay community because of its post-partum medicinal properties. Its various pharmaceutical applications cause an excessive harvesting and lead to serious shortage in natural habitat. Thus, this in vitro propagation study investigated the effects of different plant growth regulators (PGRs) on in vitro leaf and stem explants of L. pumila.
METHODS: The capabilities of callus, shoot, and root formation were evaluated by culturing both explants on Murashige and Skoog (MS) medium supplemented with various PGRs at the concentrations of 0, 1, 3, 5, and 7 mg/L.
RESULTS: Medium supplemented with 3 mg/L indole-3-butyric acid (IBA) showed the optimal callogenesis from both leaf and stem explants with (72.34 ± 19.55)% and (70.40 ± 14.14)% efficacy, respectively. IBA was also found to be the most efficient PGR for root induction. A total of (50.00 ± 7.07)% and (77.78 ± 16.47)% of root formation were obtained from the in vitro stem and leaf explants after being cultured for (26.5 ± 5.0) and (30.0 ± 8.5) d in the medium supplemented with 1 and 3 mg/L of IBA, respectively. Shoot formation was only observed in stem explant, with the maximum percentage of formation ((100.00 ± 0.00)%) that was obtained in 1 mg/L zeatin after (11.0 ± 2.8) d of culture.
CONCLUSIONS: Callus, roots, and shoots can be induced from in vitro leaf and stem explants of L. pumila through the manipulation of types and concentrations of PGRs.
Fulltext Pilomatrixoma of left shoulder in an elderly female: a case report

Tan L, Ooi C, Chua H, Zulkiflee O

Malays Orthop J, 2013 Jul;7(2):48-50.
PMID: 25722828 MyJurnal DOI: 10.5704/MOJ.1307.005

We report a huge pilomatrixoma of the left shoulder in an elderly female, raising fear of malignancy. Magnetic Resonance Imaging delineated the swelling and wide surgical excision was performed. Post operative recovery was uneventful. Long term follow up is necessary in view of the possibility of recurrence and malignant transformation.
KEY WORDS: Pilomatrixoma, Pilomatricoma, Calcifying Epithelioma of Malherbe, Shoulder, Upper Limb, Elderly, Female.
Fulltext Primary lacrimal sac lymphoma with recurrence: a case report

Chai CK, Tang IP, Tan TY

Med J Malaysia, 2013 Jun;68(3):269-70.
PMID: 23749022 MyJurnal

Primary lacrimal sac lymphoma is rare. The common clinical features are epiphora and medial canthal swelling which mimic nasolacrimal duct obstruction. Histological examination is therefore important to avoid delay in diagnosis and treatment. We report a case of primary lacrimal sac lymphoma in a 72-year-old female who developed a metachronous tumour at the hard palate one year after excision of the lacrimal sac tumour.
Rate of decline of kidney function in patients with type 2 diabetes mellitus and the associated factors: a 10-year retrospective cohort study

Tan SF, Chia YC, Chinna K

Asia Pac J Public Health, 2015 Mar;27(2):NP640-9.
PMID: 23761589 DOI: 10.1177/1010539513490193

This study examines the rate of decline of estimated glomerular filtration rate (eGFR) over a 10-year period and the associated risk factors in type 2 diabetes mellitus (T2DM) patients. Medical records of T2DM patients were randomly selected. The rate of fall in eGFR (simplified modification of diet in renal disease formula) was used as a measure of decline. Univariate and multivariate analysis were performed to determine the factors associated with decline of kidney function. A total of 504 patients were selected. Mean age was 57.8 ± 9 years; 65.3% were females. The mean decline rate of eGFR was 0.89 ± 2.16 mL/min/1.73 m(2)/y. Baseline proteinuria, glycosylated hemoglobin level, duration of T2DM, and Malay race were associated with faster decline in eGFR. The expected greater deterioration in kidney function in this cohort was not seen. Treatment of proteinuria and glycemia should be optimized early to retard the decline in kidney function in patients with T2DM.
Study site: Primary care clinics, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Childhood drowning in Malaysia

Hss AS, Tan PS, Hashim L

Int J Inj Contr Saf Promot, 2014;21(1):75-80.
PMID: 23651461 DOI: 10.1080/17457300.2013.792284

This study aimed to collate data on childhood drowning in Malaysia and review existing drowning prevention measures. This study used secondary data from governmental and non-governmental agencies. All reported fatal drownings from 2000 to 2007 and all reported non-fatal drownings from 2000 to 2008 were included. Data were analysed to provide understanding of the epidemiology of drowning incidents, risk factors and available preventive efforts. On average 286 (range 248-344) children died yearly due to drowning with a death rate of 3.05 per 100,000 annually. An additional average of 207 children drowned but survived annually (1.99 per 100,000). The estimated burden of drowning in children (death and non-death) is 5 per 100,000. There was no reduction in annual drowning fatalities over time. Most drowning took place in east coast regions during the annual monsoon season. It was 3.52 (2.80-4.41) times more common in boys and most prevalent among 10-14 years. Most prevalent sites of all-age drowning were seas and rivers. Limited water safety regulations are currently available in the country. This is the first comprehensive national study in Malaysia on paediatric drowning and highlights the magnitude of the problem. It calls for concerted effort to devise effective national drowning prevention measures.
Response of exhaled nitric oxide to inhaled corticosteroids in patients with stable COPD: A systematic review and meta-analysis

Lim CS, Rani FA, Tan LE

Clin Respir J, 2018 Jan;12(1):218-226.
PMID: 27328740 DOI: 10.1111/crj.12518

INTRODUCTION: To our knowledge, no meta-analysis has investigated the response of FeNO levels to corticosteroid treatment in ex-smokers with chronic obstructive pulmonary disease (COPD).

OBJECTIVES: This meta-analysis assessed the potential role of fraction of exhaled nitric oxide (FeNO) as a biomarker for corticosteroid response in ex-smokers with stable COPD.

METHODS: Medline, Cochrane, EMBASE, Google Scholar databases were searched until November 5, 2014 using the following terms: corticosteroid, chronic obstructive pulmonary disease, COPD, nitric oxide, NO, exhaled nitric oxide. Only randomized controlled trials (RCT) or two-arm prospective studies were included. The primary outcome measure was FeNO before and after treatment with inhaled corticosteroids (ICS) in ex-smokers with COPD. Sensitivity analysis was also performed.

RESULTS: Five studies were included in the analysis with a total of 171 COPD patients. All five studies included 125 ex-smokers and two of these also included 46 current smokers. There was a significant decrease of FeNO in ex-smoking COPD patients following inhaled corticosteroid treatment (-7.51, 95% CI: -11.51 to -3.51; P =0.003); and in a population of subjects that included both smokers and ex-smokers (-1.99, 95% CI: -3.41 to -0.56; P =0.006).

CONCLUSION: Our findings indicate that FeNO levels significantly decreased with corticosteroid treatment in ex-smokers with COPD. Additional studies are required to evaluate whether concurrent smoking has significant effect on FeNO response to ICS.
Fulltext Unusual mediastinal lymph node uptake and peritoneopleural fistula demonstrated on Technetium-99m macro-aggregated human serum albumin (Tc-99m MAA) peritoneal scintigraphy in a patient with portal hypertension

Tan CJ, Thang SP, Lam WW

Med J Malaysia, 2016 04;71(2):69-71.
PMID: 27326945

Peritoneal radionuclide scan is an established imaging modality for evaluating peritoneopleural communications. In this case report, unusual mediastinal lymph node radiotracer uptake is seen in a patient with portal hypertension on peritoneal scintigraphy. This was suspected to be due to marked lymphatic enlargement from longstanding portal hypertension since childhood, permitting passage of the large Tc-99m MAA particle. The nodes were morphologically benign on CT. Mediastinal lymph node uptake on peritoneal scintigraphy is rare but should not raise undue clinical concern, particularly in a patient with chronic portal hypertension. Anatomic correlation with SPECT-CT can provide reassurance.
Simvastatin-loaded lyophilized wafers as a potential dressing for chronic wounds

Rezvanian M, Tan CK, Ng SF

Drug Dev Ind Pharm, 2016 Dec;42(12):2055-2062.
PMID: 27237190

Wafers are an established drug delivery system for application to suppurating wounds. They can absorb wound exudates and are converted into a gel, offering a moist environment that is vital for wound healing. Simvastatin-loaded lyophilized wafers were developed using sodium carboxymethyl cellulose (CMC) and methyl cellulose (MC) and evaluated for their potential in the management of chronic wounds. Simvastatin (SIM) was chosen as the model drug since it is known to accelerate wound healing by promoting angiogenesis and lymphangiogenesis. Pre-formulation studies were carried out with CMC, MC, and a mixture of CMC and MC. Wafers obtained from aqueous gels of 3% CMC and blend of CMC-MC in the % weight ratio of 2:1 and 1.5:1.5 were selected for further analysis. The formulated wafers were characterized by microscopic examination, texture analysis, hydration test, rheological studies, FTIR spectroscopy, water vapor transmission and drug release test. Among the selected formulations, simvastatin-loaded CMC-MC (2:1) wafers exhibited the most desired characteristics for wound dressing application, such as good flexibility, hardness, sponginess, and viscosity. It showed a sustained drug release, which is desirable in wound healing, and was more appropriate for suppurating wounds. In conclusion, simvastatin-loaded CMC-MC (2:1) wafers showing potential for wound dressing applications were successfully developed.
PNMA2 mediates heterodimeric interactions and antagonizes chemo-sensitizing activities mediated by members of PNMA family

Lee YH, Pang SW, Tan KO

Biochem Biophys Res Commun, 2016 Apr 22;473(1):224-229.
PMID: 27003254 DOI: 10.1016/j.bbrc.2016.03.083

PNMA2, a member of the Paraneoplastic Ma Family (PNMA), was identified through expression cloning by using anti-sera from patients with paraneoplastic disorder. Tissue expression studies showed that PNMA2 was predominantly expressed in normal human brain; however, the protein was shown to exhibit abnormal expression profile as it was found to be expressed in a number of tumour tissues obtained from paraneopalstic patients. The abnormal expression profile of PNMA2 suggests that it might play an important role in tumorigenesis; however, apart from protein expression and immunological studies, the physiological role of PNMA2 remains unclear. In order to determine potential role of PNMA2 in tumorigenesis, and its functional relationship with PNMA family members, MOAP-1 (PNMA4) and PNMA1, expression constructs encoding the respective proteins were generated for both in vitro and in vivo studies. Our investigations showed that over-expressed MOAP-1 and PNMA1 promoted apoptosis and chemo-sensitization in MCF-7 cells as evidenced by condensed nuclei and Annexin-V positive MCF-7 cells; however, the effects mediated by these proteins were significantly inhibited or abolished when co-expressed with PNMA2 in MCF-7 cells. Furthermore, co-immunoprecipitation study showed that PNMA1 and MOAP-1 failed to associate with each other but readily formed respective heterodimer with PNMA2, suggesting that PNMA2 functions as antagonist of MOAP-1 and PNMA1 through heterodimeric interaction.
Fulltext Myeloid sarcoma: An unusual and rare laryngeal presentation

Tan SN, Gendeh HS, Sani A, Mat-Baki M

Int J Surg Case Rep, 2016;21:99-103.
PMID: 26957189 DOI: 10.1016/j.ijscr.2016.02.012

Myeloid Sarcoma (MS) or Granulocytic Sarcoma is an uncommon laryngeal malignancy. It may arise from myelodysplastic syndromes, malignancy or de novo. Presentation in the larynx is rare and some may present with Acute Myeloid Leukaemia (AML) whereby the later may be asymptomatic.

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