Browse publications by year: 2017

  1. Saw MH, Hishamuddin E, Chong CL, Yeoh CB, Lim WH
    Food Chem, 2017 Jan 1;214:277-84.
    PMID: 27507476 DOI: 10.1016/j.foodchem.2016.07.084
    The effect of 0.1-0.7% (w/w) of polyglycerol esters (PGEmix-8) on palm oil crystallization was studied using focused beam reflectance measurement (FBRM) to analyze the in-line changes of crystal size distribution during the crystallization. FBRM results show that 0.1-0.5% (w/w) of PGEmix-8 did not significantly affect nucleation but slightly retarded crystal growth. The use of 0.7% (w/w) additive showed greater heterogeneous nucleation compared to those with lower dosages of additive. Crystal growth was also greatly reduced when using 0.7% (w/w) dosage. The morphological study indicated that the palm oil crystals were smaller and more even in size than when more additive was added. Isothermal crystallization studies using differential scanning calorimetry (DSC) showed increased inhibitory effects on palm oil crystal growth with increasing concentration of PGEmix-8. These results imply that PGEmix-8 is a nucleation enhancing and crystal growth retarding additive in palm oil crystallization at 0.7% (w/w) dosage.
  2. Erfanian A, Rasti B, Manap Y
    Food Chem, 2017 Jan 1;214:606-13.
    PMID: 27507516 DOI: 10.1016/j.foodchem.2016.07.116
    Calcium bioavailability from two types of enriched (calcium citrate and calcium carbonate) milks homogenized to a nano-sized particle distribution has been studied among 48 female Sprauge-dawley rats. Skim milk powder was enriched with some essential nutrients (Inulin, DHA & EPA, vitamins B6, K1, and D3) as enhancers of calcium bioavailability according to recommended dietary allowances of the West European and North American. Ovariectomized and ovariectomized-osteoporosis rats were used as a menopause and menopause-osteoporosis model, respectively. Although, nano-sized enriched milk powders had the greatest calcium bioavailability among the groups, but bioavailability of nano-sized calcium carbonate-enriched-milk was significantly (P<0.05) better than nano-sized calcium citrate-enriched-milk. Moreover, the trends were similar for bone calcium, strength and morphology. Therefore, based on the current results the calcium carbonate nano-sized enriched milk could be an effective enriched milk powder in ovariectomized-osteoporosis and ovariectomized rats as a model of menopause-osteoporosis and menopause women.
  3. Swamy SG, Kameshwar VH, Shubha PB, Looi CY, Shanmugam MK, Arfuso F, et al.
    Target Oncol, 2017 02;12(1):1-10.
    PMID: 27510230 DOI: 10.1007/s11523-016-0452-7
    Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotoxic molecules with significant side effects. Sorafenib, a multi-targeted tyrosine kinase inhibitor, is the only approved targeted drug for HCC patients. However, due to adverse side effects and limited efficacy, there is a need for the identification of novel pharmacological drugs beyond sorafenib. Several agents that target and inhibit various signaling pathways involved in HCC are currently being assessed for HCC treatment. In the present review article, we summarize the diverse signal transduction pathways responsible for initiation as well as progression of HCC and also the potential anticancer effects of selected targeted therapies that can be employed for HCC therapy.
    MeSH terms: Antineoplastic Agents/therapeutic use*; Carcinoma, Hepatocellular/drug therapy*; Carcinoma, Hepatocellular/pathology; Humans; Liver Neoplasms/drug therapy*; Liver Neoplasms/pathology; Signal Transduction; Carcinogenesis
  4. Langdon R, Docherty PD, Chiew YS, Chase JG
    Math Biosci, 2017 02;284:32-39.
    PMID: 27513728 DOI: 10.1016/j.mbs.2016.08.001
    For patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) is an essential therapy in the intensive care unit (ICU). Suboptimal PEEP levels in MV can cause ventilator induced lung injury, which is associated with increased mortality, extended ICU stay, and high cost. The ability to predict the outcome of respiratory mechanics in response to changes in PEEP would thus provide a critical advantage in personalising and improving care. Testing the potentially dangerous high pressures would not be required to assess their impact. A nonlinear autoregressive (NARX) model was used to predict airway pressure in 19 data sets from 10 mechanically ventilated ARDS patients. Patient-specific NARX models were identified from pressure and flow data over one, two, three, or four adjacent PEEP levels in a recruitment manoeuvre. Extrapolation of NARX model elastance functions allowed prediction of patient responses to PEEP changes to higher or lower pressures. NARX model predictions were more successful than those using a well validated first order model (FOM). The most clinically important results were for extrapolation up one PEEP step of 2cmH2O from the highest PEEP in the training data. When the NARX model was trained on one PEEP level, the mean RMS residual for the extrapolation PEEP level was 0.52 (90% CI: 0.47-0.57) cmH2O, compared to 1.50 (90% CI: 1.38-1.62) cmH2O for the FOM. When trained on four PEEP levels, the NARX result was 0.50 (90% CI: 0.42-0.58) cmH2O, and was 1.95 (90% CI: 1.71-2.19) cmH2O for the FOM. The results suggest that a full recruitment manoeuvre may not be required for the NARX model to obtain a useful estimate of the pressure waveform at higher PEEP levels. The methodology could thus allow clinicians to make informed decisions about ventilator PEEP settings while reducing the risk associated with high PEEP, and subsequent high peak airway pressures.
    MeSH terms: Humans; Models, Theoretical*; Respiration, Artificial*; Respiratory Distress Syndrome, Adult*
  5. Veettil SK, Lim KG, Chaiyakunapruk N, Ching SM, Abu Hassan MR
    Asian J Surg, 2017 Nov;40(6):481-489.
    PMID: 27492344 DOI: 10.1016/j.asjsur.2016.07.005
    BACKGROUND: This study aims to provide an analytical overview of the changing burden of colorectal cancer and highlight the implementable control measures that can help reduce the future burden of colorectal cancer in Malaysia.

    METHODS: We performed a MEDLINE search via OVID with the ​Medical Subject Headings (MeSH) terms "Colorectal Neoplasms"[Mesh] and "Malaysia"[Mesh], and PubMed with the key words "colorectal cancer" and "Malaysia" from 1990 to 2015 for studies reporting any clinical, societal, and economical findings associated with colorectal cancer in Malaysia. Incidence and mortality data were retrieved from population-based cancer registries/databases.

    RESULTS: In Malaysia, colorectal cancer is the second most common cancer in males and the third most common cancer in females. The economic burden of colorectal cancer is substantial and is likely to increase over time in Malaysia owing to the current trend in colorectal cancer incidence. In Malaysia, most patients with colorectal cancer have been diagnosed at a late stage, with the 5-year relative survival by stage being lower than that in developed Asian countries. Public awareness of the rising incidence of colorectal cancer and the participation rates for colorectal cancer screening are low.

    CONCLUSION: The efficiency of different screening approaches must be assessed, and an organized national screening program should be developed in a phased manner. It is essential to maintain a balanced investment in awareness programs targeting general population and primary care providers, focused on increasing the knowledge on symptoms and risk factors of colorectal cancer, awareness on benefits of screening, and promotion of healthy life styles to prevent this important disease.

    MeSH terms: Adult; Developing Countries; Ethnic Groups/statistics & numerical data*; Female; Humans; Malaysia/epidemiology; Male; Middle Aged; Socioeconomic Factors; Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/ethnology*; Colorectal Neoplasms/surgery; Incidence; Survival Analysis; Risk Assessment; Needs Assessment*; Early Detection of Cancer*
  6. Balan S, Hassali MA, Mak VSL
    Res Social Adm Pharm, 2017 May-Jun;13(3):653-655.
    PMID: 27493130 DOI: 10.1016/j.sapharm.2016.06.014
    The pediatric population is an enormously diverse segment of population varying both in size and age. The diversity caused pharmacists face various challenges primarily related to procuring, provision as well as use of drugs in this group of patients. Pediatric dose calculation is particularly a concern for pharmacists. Another challenge faced by pharmacists is unavailability of suitable formulations for pediatric use. This has also led many pharmacists to prepare extemporaneous liquid preparations, even though stability data on such preparations are scarce. Some extemporaneous preparations contain excipients which are potentially harmful in children. Besides that, inadequate labeling and drug information for pediatric drug use had not only challenged pharmacists in recommending and optimizing drug use in children, but also inadvertently caused many drugs used outside the approved terms of the product license (off-label use). Pharmacists are striving to stay connected to overcome the common and comparable challenges faced in their day to day duties and strive to maximize the safe and effective use of medicines for children.
    MeSH terms: Age Factors; Chemistry, Pharmaceutical/methods; Child; Drug Compounding/methods*; Drug Labeling; Drug Stability; Pharmaceutical Preparations/administration & dosage*; Pharmaceutical Preparations/chemistry; Excipients/chemistry; Humans; Pediatrics; Pharmaceutical Services/organization & administration*; Pharmacists/organization & administration*; Professional Role; Drug Dosage Calculations; Off-Label Use
  7. Onilude OM, Mohd Yusoff S, Emikpe BO, Tanko P, Shahrom SM, Effendy M
    J Immunoassay Immunochem, 2017;38(1):82-99.
    PMID: 27494045 DOI: 10.1080/15321819.2016.1220395
    Early and accurate diagnosis of Brucella melitensis is essential for the treatment and control of brucellosis both in animals and humans. The thrust for the development of a rapid diagnostic technique to overcome the limitations of conventional microbiological and serological tests brought about this investigation on the development and application of dot-ELISA for antigen and antibody detection in infected goats. Fifteen apparently healthy Boer aged 2-3 years which tested negative for brucellosis using PCR and ELISA, were grouped into A (10 goats infected intraocularly with 10(7) CFU of B. melitensis) and B (5 goats) as control. Discharges (ocular, nasal, and vaginal) and blood were collected at days 3, 7, 10, 14, weekly until 42 post-infection (pi) for dot-ELISA, PCR, and RBPT. Dot-ELISA detected B. melitensis antigen and antibody in group A at day 3 and 7 pi, respectively with adequate sensitivity and specificity relative to PCR and RBPT. The bacteria shedding detected from discharges at day 3 pi in the nasal and ocular route with dot-ELISA. Group B were consistently negative. Values such as speed, simplicity, field adaptability, high sensitivity, and specificity make dot-ELISA a rapid and adequate technique for diagnosis of brucellosis in B. melitensis infected goats within few hours.
    MeSH terms: Animals; Brucellosis/diagnosis; Brucellosis/immunology*; Brucellosis/veterinary; Enzyme-Linked Immunosorbent Assay/methods*; Goats/microbiology*; Immunosorbents/chemistry*; Brucella melitensis/immunology; Brucella melitensis/isolation & purification*
  8. Neoh CF, Long CM, Lim SM, Ramasamy K, Shahar S, Majeed ABA
    Geriatr Gerontol Int, 2017 Aug;17(8):1214-1220.
    PMID: 27489036 DOI: 10.1111/ggi.12849
    AIM: The present study assessed adherence, barriers, belief and awareness towards the use of medications among multi-ethnic community-dwelling older adults in Malaysia. Medication accessibility, expenditure and perceptions towards medicine labeling among older adults were also evaluated.

    METHODS: A cross-sectional study was carried out in the central region of Malaysia from January to August 2015. The older adults enrolled in an ongoing prospective community-based geriatric cohort study and prescribed with medicines were interviewed using a 50-item validated questionnaire.

    RESULTS: Of the 79 older adults interviewed, 39.2% had ≥4 prescribed medications. Most obtained their medications free-of-charge from government hospitals (66, 83.5%). Nearly half (35, 44.3%) had trouble reading labels for medicines that they had received. Chinese older adults (P = 0.001) and those with lower monthly household income (P 

    MeSH terms: Age Factors; Aged; Aged, 80 and over; Attitude to Health/ethnology*; Cross-Sectional Studies; Ethnic Groups*; Female; Humans; Malaysia; Male; Surveys and Questionnaires*; Sex Factors; Geriatric Assessment; Risk Assessment; Polypharmacy*; Medication Adherence/ethnology*; Independent Living
  9. Al-Quraishi MS, Ishak AJ, Ahmad SA, Hasan MK, Al-Qurishi M, Ghapanchizadeh H, et al.
    Med Biol Eng Comput, 2017 May;55(5):747-758.
    PMID: 27484411 DOI: 10.1007/s11517-016-1551-4
    Electromyography (EMG)-based control is the core of prostheses, orthoses, and other rehabilitation devices in recent research. Nonetheless, EMG is difficult to use as a control signal given the complex nature of the signal. To overcome this problem, the researchers employed a pattern recognition technique. EMG pattern recognition mainly involves four stages: signal detection, preprocessing feature extraction, dimensionality reduction, and classification. In particular, the success of any pattern recognition technique depends on the feature extraction stage. In this study, a modified time-domain features set and logarithmic transferred time-domain features (LTD) were evaluated and compared with other traditional time-domain features set (TTD). Three classifiers were employed to assess the two feature sets, namely linear discriminant analysis (LDA), k nearest neighborhood, and Naïve Bayes. Results indicated the superiority of the new time-domain feature set LTD, on conventional time-domain features TTD with the average classification accuracy of 97.23 %. In addition, the LDA classifier outperformed the other two classifiers considered in this study.
    MeSH terms: Adult; Algorithms; Ankle Joint/physiology*; Bayes Theorem; Electromyography/methods; Female; Humans; Male; Movement/physiology*; Pattern Recognition, Automated/methods; Robotics/methods; Signal Processing, Computer-Assisted; Discriminant Analysis; Prostheses and Implants
  10. Etti CJ, Yusof YA, Chin NL, Mohd Tahir S
    J Diet Suppl, 2017 Mar 04;14(2):132-145.
    PMID: 27487244
    The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.
    MeSH terms: Drug Compounding/methods*; Powders/chemistry*; Tablets/chemistry*; Porosity; Compressive Strength; Primulaceae/chemistry*
  11. Khodari SNK, Noordin MI, Chan L, Chik Z
    Curr Drug Deliv, 2017;14(5):690-695.
    PMID: 27480118 DOI: 10.2174/1567201813666160801113302
    BACKGROUND: Topical local anaesthetic cream was reported to be useful for pain relief for cutaneous procedures such as minor surgery and venipuncture.

    OBJECTIVE: The aim of this study was to evaluate the effectiveness of new formulation of lidocaine topical anaesthetic using palm oil base, HAMIN® and to determine how fast this new formulation produces adequate numbness compared to the currently used EMLA cream, in the University of Malaya Medical Centre (UMMC) set-up.

    METHOD: The skin permeation test was conducted by using Franz type diffusion cell and pain assessment was carried out in healthy subject by using Verbal Rating Score (VRS) and Visual Analogue Score (VAS) evaluation.

    RESULT: Result of permeation test demonstrated that the cumulative amount of lidocaine released from HAMIN® cream was increased with time and slightly higher than EMLA cream. The clinical study showed that HAMIN® single lidocaine cream can produces numbness through venepuncture procedure and comparable with EMLA cream which is a combination therapy for local anaesthetic (lidocaine and prilocaine).

    CONCLUSION: It can be concluded that HAMIN® Lidocaine cream is suitable for cream preparation especially for topical application and it can be regarded as an achievement in palm oil and medical industries.

    MeSH terms: Anesthesia, Local; Anesthetics, Local; Hypesthesia; Lidocaine; Ointments; Pain; Pain Measurement; Prilocaine; Minor Surgical Procedures; Phlebotomy; Pain Management; Healthy Volunteers
  12. Escobar MA, Tehranchi R, Karim FA, Caliskan U, Chowdary P, Colberg T, et al.
    Haemophilia, 2017 Jan;23(1):67-76.
    PMID: 27480487 DOI: 10.1111/hae.13041
    INTRODUCTION: Surgery in patients with haemophilia B carries a high risk of excessive bleeding and requires adequate haemostatic control until wound healing. Nonacog beta pegol, a long-acting recombinant glycoPEGylated factor IX (FIX), was used in the perioperative management of patients undergoing major surgery.
    AIM: To evaluate the efficacy and safety of nonacog beta pegol in patients with haemophilia B who undergo major surgery.
    METHODS: This was an open-label, multicentre, non-controlled surgery trial aimed at assessing peri- and postoperative efficacy and safety of nonacog beta pegol in 13 previously treated patients with haemophilia B. All patients received a preoperative nonacog beta pegol bolus injection of 80 IU kg-1 . Postoperatively, the patients received fixed nonacog beta pegol doses of 40 IU kg-1 , repeated at the investigator's discretion. Safety assessments included monitoring of immunogenicity and adverse events.
    RESULTS: Intraoperative haemostatic effect was rated 'excellent' or 'good' in all 13 cases. Apart from the preoperative injection, none of the patients needed additional doses of nonacog beta pegol on the day of surgery. The median number of postoperative doses of nonacog beta pegol was 2.0 from days 1 to 6 and 1.5 from days 7 to 13. No unexpected intra- or postoperative complications were observed including deaths or thromboembolic events. No patients developed inhibitors.
    CONCLUSIONS: These results indicated that nonacog beta pegol was safe and effective in the perioperative setting, allowing major surgical interventions in patients with haemophilia B with minimal peri- and postoperative concentrate consumption and infrequent injections as reported with standard FIX products.
    KEYWORDS: Phase III; factor IX; haemophilia B; long-acting recombinant factor IX; nonacog beta pegol; surgery
    MeSH terms: Hemophilia B; Factor IX; Hemostasis; Hemostatics; Humans; Polyethylene Glycols; Postoperative Complications; Recombinant Proteins; Research Personnel; Wound Healing
  13. Too CL, Murad S, Hansson M, Alm LM, Dhaliwal JS, Holmdahl R, et al.
    Arthritis Rheumatol, 2017 01;69(1):58-69.
    PMID: 27483449 DOI: 10.1002/art.39827
    OBJECTIVE: Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects.

    METHODS: A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fibα563-583, Fibα580-600, Fibβ36-52, Fibβ62-81a, Fibβ62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%.

    RESULTS: Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibβ62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [Pcorr ] = 1.06 × 10-8 ) and CitCII355-378 (17% versus 13%, Pcorr  = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, Pcorr  = 1.91 × 10-4 ), Fibβ62-81b (15% versus 30%, Pcorr  = 2.47 × 10-22 ), and Eno5-21 (23% versus 50%, Pcorr  = 3.64 × 10-57 ) were significantly lower.

    CONCLUSION: Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.

    MeSH terms: Adolescent; Adult; Aged; Antibody Specificity*; Arthritis, Rheumatoid/immunology*; Autoantibodies/immunology*; Female; Humans; Malaysia; Male; Middle Aged; Peptides, Cyclic/immunology*; Sweden; Case-Control Studies; Young Adult
  14. Ooi SS, Mak JW, Chen DK, Ambu S
    Ind Health, 2017 Feb 07;55(1):35-45.
    PMID: 27476379 DOI: 10.2486/indhealth.2015-0218
    The free-living protozoan Acanthamoeba is an opportunistic pathogen that is ubiquitous in our environment. However, its role in affecting indoor air quality and ill-health of indoor occupants is relatively unknown. The present study investigated the presence of Acanthamoeba from the ventilation system and its correlation with other indoor air quality parameters, used in the industry code of practice and its potential as an indicator for indoor air quality. Indoor air quality assessments were carried out in nine commercial buildings with approval from the building management, and the parameters assessed were as recommended by the Department of Occupational Safety and Health. The presence of Acanthamoeba was determined through dust swabs from the ventilation system and indoor furniture. Logistic regression was performed to study the correlation between assessed parameters and occupants' complaints. A total of 107 sampling points were assessed and 40.2% of the supplying air diffuser and blowing fan and 15% of the furniture were positive for cysts. There was a significant correlation between Acanthamoeba detected from the ventilation system with ambient total fungus count (r=0.327; p=0.01) and respirable particulates (r=0.276; p=0.01). Occupants' sick building syndrome experience also correlated with the presence of Acanthamoeba in the ventilation system (r=0.361; p=0.01) and those detected on the furniture (r=0.290; p=0.01). Logistic regression showed that there was a five-fold probability of sick building syndrome among occupants when Acanthamoeba was detected in the ventilation system.
    MeSH terms: Acanthamoeba/isolation & purification*; Amebiasis/epidemiology*; Humans; Opportunistic Infections; Ventilation*; Logistic Models; Air Pollution, Indoor/analysis*; Sick Building Syndrome*
  15. Rayegan S, Dehpour AR, Sharifi AM
    Metab Brain Dis, 2017 02;32(1):41-49.
    PMID: 27476541 DOI: 10.1007/s11011-016-9883-1
    Overproduction of reactive oxygen species (ROS) by NADPH oxidase (NOX) activation has been considered the essential mechanism induced by hyperglycemia in various tissues. However, there is no comprehensive study on the role of NOXs in high glucose (HG)-induced toxic effect in neural tissues. Recently, a therapeutic strategy in oxidative related pathologies has been introduced by blocking the undesirable actions of NOX enzymes by small molecules. The protective roles of Statins in ameliorating oxidative stress by NOX inhibition have been shown in some tissues except neural. We hypothesized then, that different NOXs may have role in HG-induced neural cell injury. Furthermore, we postulate that Atorvastatin as a small molecule may modulate this NOXs activity to protect neural cells. Undifferentiated PC12 cells were treated with HG (140 mM/24 h) in the presence and absence of Atorvastatin (1 μM/96 h). The cell viability was measured by MTT assay and the gene and protein expressions profile of NOX (1-4) were determined by RT-PCR and western blotting, respectively. Levels of ROS and malondialdehyde (MDA) were also evaluated. Gene and protein expression levels of NOX (1-4) and consequently ROS and MDA levels were elevated in HG-treated PC12 cells. Atorvastatin could significantly decrease HG-induced NOXs, ROS and MDA elevation and improve impaired cell viability. It can be concluded that HG could elevate NOXs activity, ROS and MDA levels in neural tissues and Atorvastatin as a small molecule NOX inhibitor drug may prevent and delay diabetic complications, particularly neuropathy.
    MeSH terms: Atorvastatin Calcium/pharmacology*; Animals; Cell Survival/drug effects; Glucose/pharmacology*; Malondialdehyde/metabolism; Neurons/drug effects*; Neurons/metabolism; Lipid Peroxidation/drug effects; PC12 Cells; Reactive Oxygen Species/metabolism; Oxidative Stress/drug effects*; Neuroprotective Agents/pharmacology*; NADPH Oxidase/metabolism*; Rats
  16. Yahaya N, Sanagi MM, Abd Aziz N, Wan Ibrahim WA, Nur H, Loh SH, et al.
    Biomed Chromatogr, 2017 Feb;31(2).
    PMID: 27474795 DOI: 10.1002/bmc.3803
    A rapid dispersive micro-solid phase extraction (D-μ-SPE) combined with LC/MS/MS method was developed and validated for the determination of ketoconazole and voriconazole in human urine and plasma samples. Synthesized mesoporous silica MCM-41 was used as sorbent in d-μ-SPE of the azole compounds from biological fluids. Important D-μ-SPE parameters, namely type desorption solvent, extraction time, sample pH, salt addition, desorption time, amount of sorbent and sample volume were optimized. Liquid chromatographic separations were carried out on a Zorbax SB-C18 column (2.1 × 100 mm, 3.5 μm), using a mobile phase of acetonitrile-0.05% formic acid in 5 mm ammonium acetate buffer (70:30, v/v). A triple quadrupole mass spectrometer with positive ionization mode was used for the determination of target analytes. Under the optimized conditions, the calibration curves showed good linearity in the range of 0.1-10,000 μg/L with satisfactory limit of detection (≤0.06 μg/L) and limit of quantitation (≤0.3 μg/L). The proposed method also showed acceptable intra- and inter-day precisions for ketoconazole and voriconazole from urine and human plasma with RSD ≤16.5% and good relative recoveries in the range 84.3-114.8%. The MCM-41-D-μ-SPE method proved to be rapid and simple and requires a small volume of organic solvent (200 μL); thus it is advantageous for routine drug analysis.
    MeSH terms: Antifungal Agents/blood*; Antifungal Agents/urine*; Chromatography, High Pressure Liquid/economics; Chromatography, High Pressure Liquid/methods; Humans; Ketoconazole/blood*; Ketoconazole/urine*; Silicon Dioxide/chemistry; Solid Phase Microextraction/economics; Solid Phase Microextraction/methods*; Tandem Mass Spectrometry/economics; Tandem Mass Spectrometry/methods; Limit of Detection; Voriconazole/blood*; Voriconazole/urine*
  17. Kuan YH, Nafchi AM, Huda N, Ariffin F, Karim AA
    J Sci Food Agric, 2017 Mar;97(5):1663-1671.
    PMID: 27465360 DOI: 10.1002/jsfa.7970
    BACKGROUND: Previous studies have indicated that duck feet are a rich source of gelatin extractable from avian sources. In this study, the physicochemical and functional properties of avian gelatin extracted from duck feet (DFG) with acetic acid were compared with those of commercial bovine gelatin (BG).

    RESULTS: The yield of DFG obtained in this study was 7.01 ± 0.31%. High-performance liquid chromatography analysis indicated that the imino acid content was slightly lower for DFG compared with BG (P < 0.05). Differences in molecular size and amino acids between DFG and BG were also observed. The isoelectric points of DFG and BG were at pH 8 and 5 respectively, and the overall protein solubility of BG was higher than that of DFG. Gels prepared from BG exhibited higher bloom strength, viscosity and clarity and were darker in colour compared with DFG gels (P < 0.05). The gelling and melting points of BG were 21.8 and 29.47 °C respectively, while those of DFG were 20.5 and 27.8 °C respectively. BG exhibited slightly better emulsifying and foaming properties compared with DFG.

    CONCLUSION: Although some differences between DFG and BG were observed, the disparities were small, which indicates that DFG could be exploited commercially as an alternative source of gelatin. © 2016 Society of Chemical Industry.

    MeSH terms: Amino Acids/analysis; Animals; Cattle*; Ducks*; Foot; Gelatin/chemistry*; Imino Acids/analysis; Rheology; Solubility; Acetic Acid; Food Quality
  18. Mohd Fauzi F, John CM, Karunanidhi A, Mussa HY, Ramasamy R, Adam A, et al.
    J Ethnopharmacol, 2017 Feb 02;197:61-72.
    PMID: 27452659 DOI: 10.1016/j.jep.2016.07.058
    ETHNOPHARMACOLOGICAL RELEVANCE: Cassia auriculata (CA) is used as an antidiabetic therapy in Ayurvedic and Siddha practice. This study aimed to understand the mode-of-action of CA via combined cheminformatics and in vivo biological analysis. In particular, the effect of 10 polyphenolic constituents of CA in modulating insulin and immunoprotective pathways were studied.

    MATERIALS AND METHODS: In silico target prediction was first employed to predict the probability of the polyphenols interacting with key protein targets related to insulin signalling, based on a model trained on known bioactivity data and chemical similarity considerations. Next, CA was investigated in in vivo studies where induced type 2 diabetic rats were treated with CA for 28 days and the expression levels of genes regulating insulin signalling pathway, glucose transporters of hepatic (GLUT2) and muscular (GLUT4) tissue, insulin receptor substrate (IRS), phosphorylated insulin receptor (AKT), gluconeogenesis (G6PC and PCK-1), along with inflammatory mediators genes (NF-κB, IL-6, IFN-γ and TNF-α) and peroxisome proliferators-activated receptor gamma (PPAR-γ) were determined by qPCR.

    RESULTS: In silico analysis shows that several of the top 20 enriched targets predicted for the constituents of CA are involved in insulin signalling pathways e.g. PTPN1, PCK-α, AKT2, PI3K-γ. Some of the predictions were supported by scientific literature such as the prediction of PI3K for epigallocatechin gallate. Based on the in silico and in vivo findings, we hypothesized that CA may enhance glucose uptake and glucose transporter expressions via the IRS signalling pathway. This is based on AKT2 and PI3K-γ being listed in the top 20 enriched targets. In vivo analysis shows significant increase in the expression of IRS, AKT, GLUT2 and GLUT4. CA may also affect the PPAR-γ signalling pathway. This is based on the CA-treated groups showing significant activation of PPAR-γ in the liver compared to control. PPAR-γ was predicted by the in silico target prediction with high normalisation rate although it was not in the top 20 most enriched targets. CA may also be involved in the gluconeogenesis and glycogenolysis in the liver based on the downregulation of G6PC and PCK-1 genes seen in CA-treated groups. In addition, CA-treated groups also showed decreased cholesterol, triglyceride, glucose, CRP and Hb1Ac levels, and increased insulin and C-peptide levels. These findings demonstrate the insulin secretagogue and sensitizer effect of CA.

    CONCLUSION: Based on both an in silico and in vivo analysis, we propose here that CA mediates glucose/lipid metabolism via the PI3K signalling pathway, and influence AKT thereby causing insulin secretion and insulin sensitivity in peripheral tissues. CA enhances glucose uptake and expression of glucose transporters in particular via the upregulation of GLUT2 and GLUT4. Thus, based on its ability to modulate immunometabolic pathways, CA appears as an attractive long term therapy for T2DM even at relatively low doses.

    MeSH terms: Animals; Cassia/chemistry*; Diabetes Mellitus, Experimental/drug therapy; Diabetes Mellitus, Experimental/metabolism; Diabetes Mellitus, Type 2/drug therapy*; Diabetes Mellitus, Type 2/metabolism; Insulin/metabolism; Liver/drug effects; Liver/metabolism; Plant Extracts/pharmacology*; Signal Transduction/drug effects; Rats, Sprague-Dawley; Phosphatidylinositol 3-Kinases/metabolism; PPAR gamma/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Glucose Transporter Type 2/metabolism; Glucose Transporter Type 4/metabolism; Rats; Insulin Receptor Substrate Proteins/metabolism
  19. Yeap SK, Abu N, Akthar N, Ho WY, Ky H, Tan SW, et al.
    Integr Cancer Ther, 2017 09;16(3):373-384.
    PMID: 27458249 DOI: 10.1177/1534735416660383
    Flavokawain B (FKB) is known to possess promising anticancer abilities. This is demonstrated in various cancer cell lines including HeLa cells. Cervical cancer is among the most widely diagnosed cancer among women today. Though FKB has been shown to be effective in treating cancer cells, the exact molecular mechanism is still unknown. This study is aimed at understanding the effects of FKB on HeLa cells using a microarray-based mRNA expression profiling and proteome profiling of stress-related proteins. The results of this study suggest that FKB induced cell death through p21-mediated cell cycle arrest and activation of p38. However, concurrent activation of antioxidant-related pathways and iron sequestration pathway followed by activation of ER-resident stress proteins clearly indicate that FKB failed to induce apoptosis in HeLa cells via oxidative stress. This effect implies that the protection of HeLa cells by FKB from H2O2-induced cell death is via neutralization of reactive oxygen species.
    MeSH terms: Antioxidants/metabolism*; Uterine Cervical Neoplasms/drug therapy*; Uterine Cervical Neoplasms/metabolism; Female; Flavonoids/pharmacology*; HeLa Cells; Humans; Hydrogen Peroxide/pharmacology; RNA, Messenger/metabolism; Gene Expression/drug effects*; Apoptosis/drug effects*; Reactive Oxygen Species/metabolism; Oxidative Stress/drug effects; Cell Line, Tumor; p38 Mitogen-Activated Protein Kinases/metabolism; Cyclin-Dependent Kinase Inhibitor p21/metabolism; Cell Cycle Checkpoints/drug effects
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