Browse publications by year: 2016

  1. Islam MA, Wong KK, Sasongko TH, Gan SH, Wong JS
    Eur J Rheumatol, 2016 Sep;3(3):139-141.
    PMID: 27733946 DOI: 10.5152/eurjrheum.2015.0068
    Here we present a case report of three familial primary antiphospholipid syndrome (PAPS) patients from Malaysia. The three familial patients comprised two females and one male with a mean age of 26.3 years. The first diagnosis was made between 2005 and 2009, and all patients demonstrated deep vein thrombosis, high levels of IgM and IgG anticardiolipin antibodies, and received warfarin treatment international normalized ratio (INR) 2.0-3.0. The patients ceased to show clinical symptoms after treatment. Recently (August 2014), we investigated whether the levels of antiphospholipid antibodies remained elevated, and we found that seronegativity occurred in the patients. We suspect that prolonged anticoagulant treatment might be one of the causes of reduced levels of antiphospholipid antibodies in these familial PAPS patients.
    MeSH terms: Adult; Anticoagulants; Female; Humans; Immunoglobulin G; Immunoglobulin M; Malaysia; Male; Warfarin; Antiphospholipid Syndrome*; Antibodies, Antiphospholipid; Antibodies, Anticardiolipin; International Normalized Ratio; Venous Thrombosis
  2. Lee CH, Sapuan SM, Lee JH, Hassan MR
    Springerplus, 2016;5(1):1680.
    PMID: 27733982
    A study of the melt volume flow rate (MVR) and the melt flow rate (MFR) of kenaf fibre (KF) reinforced Floreon (FLO) and magnesium hydroxide (MH) biocomposites under different temperatures (160-180 °C) and weight loadings (2.16, 5, 10 kg) is presented in this paper. FLO has the lowest values of MFR and MVR. The increment of the melt flow properties (MVR and MFR) has been found for KF or MH insertion due to the hydrolytic degradation of the polylactic acid in FLO. Deterioration of the entanglement density at high temperature, shear thinning and wall slip velocity were the possible causes for the higher melt flow properties. Increasing the KF loadings caused the higher melt flow properties while the higher MH contents created stronger bonding for higher macromolecular chain flow resistance, hence lower melt flow properties were recorded. However, the complicated melt flow behaviour of the KF reinforced FLO/MH biocomposites was found in this study. The high probability of KF-KF and KF-MH collisions was expected and there were more collisions for higher fibre and filler loading causing lower melt flow properties.
  3. Nor MR, Abdullah AT, Ali AK
    Springerplus, 2016;5(1):1683.
    PMID: 27733985
    Malaysia is a multicultural state comprising three main races: Malays, Chinese and Indians. The three main religions are Islam, Buddhism and Hinduism. Other religions such as Sikhism and Christianity are also practised. Muslims are the majority comprising 67 % of the population.
  4. Loke P, Lim YAL
    Cell Host Microbe, 2016 10 12;20(4):417-419.
    PMID: 27736641 DOI: 10.1016/j.chom.2016.09.016
    Gut commensals profoundly affect host immunity and intestinal homeostasis, but the impact of commensal eukaryotic protozoans is poorly understood. In a recent Cell paper, Chudnovskiy et al. (2016) identify a commensal protozoan, Tritrichomonas musculis, that can enhance anti-bacterial defenses, but at the cost of increasing intestinal inflammation.
    MeSH terms: Homeostasis/immunology; Humans; Inflammation/immunology*; Intestines/immunology*
  5. Abdul Ghani ZD, Husin JM, Rashid AH, Shaari K, Chik Z
    J Ethnopharmacol, 2016 Oct 7.
    PMID: 27725236 DOI: 10.1016/j.jep.2016.10.022
    Piper Betle L. (PB) belongs to the Piperaceae family. The presence of a fairly large quantity of diastase in the betel leaf is deemed to play an important role in starch digestion and calls for the study of weight loss activities and metabolite profile from PB leaf extracts using metabolomics approach to be performed. PB dried leaves were extracted with 70% ethanol and the extracts were subjected to five groups of rats fed with high fat (HF) and standard diet (SD). They were then fed with the extracts in two doses and compared with a negative control group given water only according to the study protocol. The body weights and food intakes were monitored every week. At the end of the study, blood serum of the experimental animal was analysed to determine the biochemical and metabolite changes. PB treated group demonstrated inhibition of body weight gain without showing an effect on the food intake. In serum bioassay, the PB treated group (HF/PB (100mg/kg and 500mg/kg) showed an increased in glucose and cholesterol levels compared to the Standard Diet (SD/WTR) group, a decrease in LDL level and increase in HDL level when compared with High Fat Diet (HF/WTR) group. For metabolite analysis, two separation models were made to determine the metabolite changes via group activities. The best separation of PCA serum in Model 1 and 2 was achieved in principle component 1 and principle component 2. SUS-Plot model showed that HF group was characterized by high-level of glucose, glycine and alanine. Increase in the β-hydroxybutyrate level similar with SD group animals was evident in the HF/PB(500mg/kg) group. This finding suggested that the administration of 500mg/kg PB extracts leads to increase in oxidation process in the body thus maintaining the body weight and without giving an effect on the appetite even though HF was continuously consumed by the animals until the end of the studies and also a reduction in food intake, thus maintaining their body weight although they were continuously consumed HF.
    MeSH terms: Alanine; Ethanol; Amylases; Animals; Appetite; Biological Assay; Body Weight; Cholesterol; Digestion; Eating; Glucose; Glycine; Starch; Water; Weight Gain; Weight Loss; 3-Hydroxybutyric Acid; Piper betle; Control Groups; Serum; Rats; Metabolomics; Diet, High-Fat
  6. Lim J, Razi ZR, Law J, Nawi AM, Idrus RB, Ng MH
    Cytotherapy, 2016 12;18(12):1493-1502.
    PMID: 27727016 DOI: 10.1016/j.jcyt.2016.08.003
    BACKGROUND AIMS: Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied. In this study, hWJMSCs derived from three anatomical segments of the UC are compared.

    METHODS: Three segments of the whole UC, each 3 cm in length, were identified anatomically as the maternal, middle and fetal segments. The hWJMSCs from the different segments were analyzed via trypan blue exclusion assay to determine the growth kinetics and cell viability, flow cytometry for immunophenotyping and immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of stromal cell transcriptional factors. Furthermore, the trilineage differentiation potential (osteogenic, adipogenic and chondrogenic) of these cells was also assessed.

    RESULTS: hWJMSCs isolated from the maternal and fetal segments displayed greater viability and possessed a significantly higher proliferation rate compared with cells from the middle segment. Immunophenotyping revealed that hWJMSCs derived from all three segments expressed the MSC markers CD105, CD73, CD90, CD44, CD13 and CD29, as well as HLA-ABC and HLA-DR, but were negative for hematopoietic markers CD14, CD34 and CD45. Analysis of the embryonic markers showed that all three segments expressed Nanog and Oct 3/4, but only the maternal and fetal segments expressed SSEA 4 and TRA-160. Cells from all three segments were able to differentiate into chondrogenic, osteogenic and adipogenic lineages with the middle segments showing much lower differentiation potential compared with the other two segments.

    CONCLUSIONS: hWJMSCs derived from the maternal and fetal segments of the UC are a good source of MSCs compared with cells from the middle segment because of their higher proliferation rate and viability. Fetal and maternal segments are the preferred cell source for bone regeneration.

    MeSH terms: Adult; Cell Differentiation; Cell Survival; Cells, Cultured; Flow Cytometry; Humans; Osteogenesis/physiology*; Umbilical Cord/cytology*; Biomarkers/metabolism; Immunophenotyping; Stromal Cells/cytology; Chondrogenesis/physiology*; Mesenchymal Stem Cell Transplantation/methods; Cell Proliferation; Adipogenesis/physiology*; Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/metabolism; Wharton Jelly/cytology*
  7. Thiry V, Stark DJ, Goossens B, Slachmuylder JL, Vercauteren Drubbel R, Vercauteren M
    Folia Primatol., 2016;87(3):180-196.
    PMID: 27728905
    The choice of a sleeping site is crucial for primates and may influence their survival. In this study, we investigated several tree characteristics influencing the sleeping site selection by proboscis monkeys (Nasalis larvatus) along Kinabatangan River, in Sabah, Malaysia. We identified 81 sleeping trees used by one-male and all-male social groups from November 2011 to January 2012. We recorded 15 variables for each tree. Within sleeping sites, sleeping trees were taller, had a larger trunk, with larger and higher first branches than surrounding trees. The crown contained more mature leaves, ripe and unripe fruits but had vines less often than surrounding trees. In addition, in this study, we also focused on a larger scale, considering sleeping and non-sleeping sites. Multivariate analyses highlighted a combination of 6 variables that revealed the significance of sleeping trees as well as surrounding trees in the selection process. During our boat surveys, we observed that adult females and young individuals stayed higher in the canopy than adult males. This pattern may be driven by their increased vulnerability to predation. Finally, we suggest that the selection of particular sleeping tree features (i.e. tall, high first branch) by proboscis monkeys is mostly influenced by antipredation strategies.
    MeSH terms: Animals; Behavior, Animal*; Female; Fruit; Malaysia; Male; Predatory Behavior; Sleep*; Social Behavior; Trees*; Colobinae/physiology*; Ecosystem
  8. Richardson JS, Sethi G, Lee GS, Malek SN
    BMC Complement Altern Med, 2016 Oct 12;16(1):389.
    PMID: 27729078
    Cancer has been one of the leading causes of mortality in this era. Ruta angustifolia L. Pers has been traditionally used as an abortifacient, antihelmintic, emmenagogue and ophthalmic. In Malaysia and Singapore, the local Chinese community used it for the treatment of cancer.
    MeSH terms: Humans; Lung Neoplasms*; Plant Extracts/chemistry*; Furocoumarins/isolation & purification; Furocoumarins/pharmacology*; Furocoumarins/chemistry; Signal Transduction/drug effects; Apoptosis/drug effects*; Caspases/metabolism; Ruta/chemistry*; Cell Line, Tumor; Membrane Potential, Mitochondrial/drug effects*
  9. Waziri PM, Abdullah R, Yeap SK, Omar AR, Abdul AB, Kassim NK, et al.
    J Ethnopharmacol, 2016 Dec 24;194:549-558.
    PMID: 27729282 DOI: 10.1016/j.jep.2016.10.030
    ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia.

    AIM OF THE STUDY: To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis.

    MATERIALS AND METHODS: Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using (1)H and (13)C NMR spectra. Clausenidin-induced cytotoxicity was determined by MTT assay. The morphology of hepG2 after treatment with clausenidin was determined by fluorescence and Scanning Electron Microscopy. The effect of clausenidin on the apoptotic genes and proteins were determined by real-time qPCR and protein array profiling, respectively. The involvement of the mitochondria in clausenidin-induced apoptosis was investigated using MMP, caspase 3 and 9 assays.

    RESULTS: Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells.

    CONCLUSION: Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound.

    MeSH terms: Humans; Microscopy, Electron, Scanning; Mitochondria/drug effects*; Mitochondria/metabolism; Plant Extracts/pharmacology*; Gene Expression; Apoptosis/drug effects*; Membrane Potential, Mitochondrial/drug effects; Caspase 3/metabolism; Caspase 9/metabolism; Clausena/chemistry*; Hep G2 Cells
  10. Cui Y, Song BK, Li LF, Li YL, Huang Z, Caicedo AL, et al.
    G3 (Bethesda), 2016 Dec 07;6(12):4105-4114.
    PMID: 27729434 DOI: 10.1534/g3.116.035881
    Weedy rice is a conspecific form of cultivated rice (Oryza sativa L.) that infests rice fields and results in severe crop losses. Weed strains in different world regions appear to have originated multiple times from different domesticated and/or wild rice progenitors. In the case of Malaysian weedy rice, a multiple-origin model has been proposed based on neutral markers and analyses of domestication genes for hull color and seed shattering. Here, we examined variation in pericarp (bran) color and its molecular basis to address how this trait evolved in Malaysian weeds and its possible role in weed adaptation. Functional alleles of the Rc gene confer proanthocyanidin pigmentation of the pericarp, a trait found in most wild and weedy Oryzas and associated with seed dormancy; nonfunctional rc alleles were strongly favored during rice domestication, and most cultivated varieties have nonpigmented pericarps. Phenotypic characterizations of 52 Malaysian weeds revealed that most strains are characterized by the pigmented pericarp; however, some weeds have white pericarps, suggesting close relationships to cultivated rice. Phylogenetic analyses indicate that the Rc haplotypes present in Malaysian weeds likely have at least three distinct origins: wild O. rufipogon, white-pericarp cultivated rice, and red-pericarp cultivated rice. These diverse origins contribute to high Rc nucleotide diversity in the Malaysian weeds. Comparison of Rc allelic distributions with other rice domestication genes suggests that functional Rc alleles may confer particular fitness benefits in weedy rice populations, for example, by conferring seed dormancy. This may promote functional Rc introgression from local wild Oryza populations.
    MeSH terms: Adaptation, Biological; Phenotype; Phylogeny; Pigmentation/genetics*; Oryza/classification; Oryza/genetics*; Genetic Variation; Genes, Plant; Sequence Analysis, DNA; Crops, Agricultural/genetics; Genome, Plant; Evolution, Molecular*; Genetic Association Studies*
  11. Khan Y, Pandy V
    Front Pharmacol, 2016;7:352.
    PMID: 27729866
    Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.
    MeSH terms: Administration, Oral; Ethanol; Methanol; Alcoholism; Animals; Chronic Disease; Compulsive Behavior; Fruit; Phytotherapy; Plant Extracts; Pyrazines; Morinda; Mice
  12. Kam MY, Chai LC, Chin CF
    Springerplus, 2016;5(1):1657.
    PMID: 27730019
    Aponogeton ulvaceus Baker (Aponogetonaceae) is a commercially important ornamental aquatic plant species with traditional medicinal uses. Due to the low survival rate of seedlings, propagation by conventional means has been met with many difficulties. In this study, botanical aspects of A. ulvaceus were examined with regards to the morphology, anatomy and physiology of the plant and an efficient protocol for its in vitro propagation using immature tuber explants has been established. The existence of glandular trichomes on the leaves was discovered and the occurrence of circumnutation in A. ulvaceus has been demonstrated. Immature tuber segments with meristems were cultured on MS medium supplemented with various combinations (0, 1, 2, and 3 mg/L) of BAP and NAA for callus induction. The highest percentage of callus production (100 %) was obtained in two different treatments: 1 mg/L BAP and 3 mg/L NAA, and 2 mg/L BAP and 3 mg/L NAA. For shoot and root organogenesis, the combination of 1 mg/L BAP and 1 mg/L NAA was shown to be significant for A. ulvaceus regeneration when compared to control, which yields a mean shoot and root number of 22.50 and 29.50 respectively. The current protocol is the first reported successful establishment of in vitro clonal propagation of A. ulvaceus.
  13. Ismail MD, Ahmad WA, Leschke M, Waliszewski M, Boxberger M, Abidin IZ, et al.
    Springerplus, 2016;5(1):1668.
    PMID: 27730026
    Percutaneous coronary interventions (PCI) in coronary artery disease (CAD) with very small vessel diameters remains controversial and challenging. These lesions are usually more diffuse, calcified and tortuous. The usage of thin strut bare metal stents (BMS) with excellent crossing profiles in a very small caliber coronary lesions has increased the likelihood of procedural success.
  14. Chong TM, Yin WF, Chen JW, Mondy S, Grandclément C, Faure D, et al.
    AMB Express, 2016 Dec;6(1):95.
    PMID: 27730570
    Trace metals are required in many cellular processes in bacteria but also induce toxic effects to cells when present in excess. As such, various forms of adaptive responses towards extracellular trace metal ions are essential for the survival and fitness of bacteria in their environment. A soil Pseudomonas putida, strain S13.1.2 has been isolated from French vineyard soil samples, and shown to confer resistance to copper ions. Further investigation revealed a high capacity to tolerate elevated concentrations of various heavy metals including nickel, cobalt, cadmium, zinc and arsenic. The complete genome analysis was conducted using single-molecule real-time (SMRT) sequencing and the genome consisted in a single chromosome at the size of 6.6 Mb. Presence of operons and gene clusters such as cop, cus, czc, nik, and asc systems were detected and accounted for the observed resistance phenotypes. The unique features in terms of specificity and arrangements of some genetic determinants were also highlighted in the study. Our findings has provided insights into the adaptation of this strain to accumulation and persistence of copper and other heavy metals in vineyard soil environment.
    MeSH terms: Arsenic; Cadmium; Chromosomes; Cobalt; Copper; Ions; Nickel; Operon; Soil; Trace Elements; Zinc; Pseudomonas putida; Metals, Heavy; Farms
  15. Mok PS, Ch'ng DH, Ong SP, Numata K, Sudesh K
    AMB Express, 2016 Dec;6(1):97.
    PMID: 27730572
    Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is one of the polyhydroxyalkanoate (PHA) copolymers which can be degraded by lipases. In this study, the depolymerizing activity of different known commercial lipases was investigated via microassay using P(3HB-co-92 mol % 4HB) thin film as substrate. Non-enzymatic hydrolysis occurred under conditions in which buffers with pH 12 and 13 were added or temperature of 50 °C and above. Different concentrations of metal ions or detergents alone did not cause the film hydrolysis. The depolymerizing activity of lipases on P(3HB-co-4HB) was optimum in the pH range of 6-8 and at temperatures between 30 and 50 °C. Addition of metal ions and detergents in different concentrations was also shown to cause variable effects on the depolymerizing activity of commercial lipases. Pancreatic extracts from both mouse and chicken showed similar depolymerizing activity as the commercial lipases on the P(3HB-co-4HB) film. The presence of lipolytic enzymes in the organ extracts was confirmed with another lipase activity assay, p-nitrophenyl laurate assay. For the first time this has produced a direct evidence for the involvement of lipase-like enzymes from animal in the degradation of this PHA. Lipase is most likely the enzyme from pancreas that was involved in the degradation.
    MeSH terms: Animals; Chickens; Detergents; Hydrolysis; Hydroxybutyrates; Ions; Laurates; Lipase; Metals; Pancreatic Extracts; Polyesters; Temperature; 3-Hydroxybutyric Acid; Mice; Polyhydroxyalkanoates
  16. Sukhlecha A
    Indian J Med Ethics, 2016 Oct-Dec;1(4):264.
    PMID: 27731301
    Incentives, pay hikes and timely promotions enhance the job performance of an employee. In medical institutes, too, satisfied teachers would train students in a better way leading to better equipped doctors and ultimately, greater patient satisfaction. A study in Malaysia links high levels of satisfaction of employees with good salary, promotions, and incentives.
    MeSH terms: Career Mobility*; Education, Medical*; Faculty, Medical*; Humans; Malaysia; Motivation; Salaries and Fringe Benefits; Schools, Medical*
  17. Osthoff M, Siegemund M, Balestra G, Abdul-Aziz MH, Roberts JA
    Swiss Med Wkly, 2016;146:w14368.
    PMID: 27731492 DOI: 10.4414/smw.2016.14368
    Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for "prime time", as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patient-centred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care.
    MeSH terms: Anti-Bacterial Agents/therapeutic use*; Humans; Infusions, Intravenous/methods*; Intensive Care Units; Microbial Sensitivity Tests; Critical Illness; Outcome Assessment (Health Care); beta-Lactams/pharmacokinetics; beta-Lactams/therapeutic use*
  18. Rehman A, Abbasi MA, Siddiqui SZ, Mohyuddin A, Nadeem S, Shah SA
    Pak J Pharm Sci, 2016 Sep;29(5):1489-1496.
    PMID: 27731801
    New potent organic compounds were synthesized with an aim of good biological activities such as antibacterial and anti-enzymatic. Three series of sulfonamide derivatives were synthesized by treating N-alkyl/aryl substituted amines (2a-f) with 4-chlorobenzensulfonyl chloride (1) to yield N-alkyl/aryl-4-chlorobenzenesulfonamide(3af) that was then derivatized by gearing up with ethyl iodide (4), benzyl chloride (5) and 4-chlorobenzyl chloride (6) using sodium hydride as base to initialize the reaction in a polar aprotic solvent (DMF) to synthesize the derivatives, 7a-f, 8af and 9a-f respectively. Structure elucidation was brought about by IR, 1H-NMR and EIMS spectra for all the synthesized molecules which were evaluated for their antibacterial activities and inhibitory potentials for certain enzymes.
    MeSH terms: Anti-Bacterial Agents/chemical synthesis*; Anti-Bacterial Agents/pharmacology*; Bacteria/drug effects*; Bacteria/growth & development; Chymotrypsin/antagonists & inhibitors; Enzyme Inhibitors/chemical synthesis*; Enzyme Inhibitors/pharmacology*; Spectrophotometry, Infrared; Mass Spectrometry; Structure-Activity Relationship; Sulfonamides/chemical synthesis*; Sulfonamides/pharmacology*; Drug Design*; Molecular Structure; Serine Proteinase Inhibitors/chemical synthesis; Serine Proteinase Inhibitors/pharmacology; Lipoxygenase Inhibitors/chemical synthesis; Lipoxygenase Inhibitors/pharmacology; Proton Magnetic Resonance Spectroscopy
  19. Ng RT, Lee WS, Ang HL, Teo KM, Yik YI, Lai NM
    Cochrane Database Syst Rev, 2016 Oct 12;10(10):CD010873.
    PMID: 27732736
    BACKGROUND: Childhood constipation is a common problem with substantial health, economic and emotional burdens. Existing therapeutic options, mainly pharmacological, are not consistently effective, and some are associated with adverse effects after prolonged use. Transcutaneous electrical stimulation (TES), a non-pharmacological approach, is postulated to facilitate bowel movement by modulating the nerves of the large bowel via the application of electrical current transmitted through the abdominal wall.

    OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.

    SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .

    SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.

    DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes.

    MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.There were no significant differences between TES and the sham control group for the following outcomes: i).number of children with > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53, one study, 42 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision ), ii). number of children with improved colonic transit assessed radiologically (RR 5.00, 95% CI 0.79 to 31.63; one study, 21 participants) (Quality of evidence: very low, due to high risk of bias, serious imprecision and indirectness of the outcome). However, mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was significantly higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants) (Quality of evidence: very low, due to high risk of bias , serious imprecision and indirectness of the outcome). There was no significant difference between the two groups in the number of children with improved soiling-related symptoms (RR 2.08, 95% CI 0.86 to 5.00; one study, 25 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision). There was no significant difference in the number of children with improved quality of life (QoL) (RR 4.00, 95% CI 0.56 to 28.40; one study, 16 participants) (Quality of evidence: very low, due to high risk of bias issues and serious imprecision ). There were also no significant differences in in self-perceived (MD 5.00, 95% CI -1.21 to 11.21) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants for both outcomes) (Quality of evidence for both outcomes: very low, due to high risk of bias and serious imprecision). No adverse effects were reported in the included study.

    AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.

    MeSH terms: Adolescent; Child; Chronic Disease; Constipation/therapy*; Transcutaneous Electric Nerve Stimulation*; Humans; Randomized Controlled Trials as Topic
  20. Mohamad Isa II, Abu Bakar S, Md Tohid SF, Mat Jais AM
    J Ethnopharmacol, 2016 Dec 24;194:469-474.
    PMID: 27732902 DOI: 10.1016/j.jep.2016.10.033
    ETHNOPHARMACOLOGICAL RELEVANCE: Haruan, Channa striatus, is a freshwater fish which has been well-known locally to accelerate wound healing during post-operative and post-partum periods. The fish extract also has potent anti-inflammatory and analgesic properties.

    AIM OF THE STUDY: To assess topical anti-inflammatory effect of Haruan cream on 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced chronic-like dermatitis in mice.

    MATERIALS AND METHODS: Male ICR mice were randomized into six groups of five mice each: acetone (vehicle), TPA alone (negative control), three Haruan treatment groups (Haruan 1%, Haruan 5% and Haruan 10%) and hydrocortisone 1% (positive control). Briefly, both surfaces of mouse ears were applied with TPA (2.5μg/20μl acetone) for five times on alternate days and with Haruan or hydrocortisone 1% cream for the last three days. Mouse ear thickness was measured 24h after final treatment with the cream and the ears were harvested for further histological analysis and gene expression studies of TNF-α by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR).

    RESULTS: Topical application of Haruan cream had reduced the mouse ear thickness 18.1-28%) with comparable effect to the positive control. In addition, histopathological comparison had shown evident reduction in various parameters of cutaneous inflammation including dermal oedema, inflammatory cells infiltration and proliferation of epidermal keratinocytes. Furthermore, TPA application had resulted in the up-regulation of TNF-α gene expression by 353-fold, which was subsequently down-regulated by the Haruan cream (34- to 112-fold).

    CONCLUSION: Haruan is an effective topical anti-inflammatory agent in this mouse model of chronic-like dermatitis, thus suggesting its potential as a non-steroidal treatment option for chronic inflammatory dermatoses.

    MeSH terms: Animals; Chronic Disease; Dermatitis/pathology; Dermatitis/prevention & control*; Disease Models, Animal*; Fishes*; Gene Expression Regulation; Male; Medicine, Traditional*; Mice, Inbred ICR; Tumor Necrosis Factor-alpha/genetics*; Down-Regulation; Cytokines/genetics; Inflammation Mediators/metabolism; Mice
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