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  1. Fulltext Biochemical characterization and 1H NMR based metabolomics revealed Melicope lunu-ankenda leaf extract a potent anti-diabetic agent in rats
    Al-Zuaidy MH, Mumtaz MW, Hamid AA, Ismail A, Mohamed S, Razis AFA
    BMC Complement Altern Med, 2017 Jul 10;17(1):359.
    PMID: 28693595 DOI: 10.1186/s12906-017-1849-2
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the use of medicinal plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one of the Melicope species belonging to the family Rutaceae. In traditional medicines, its leaves and flowers are known to exhibit prodigious health benefits. The present study aimed at investigating anti-diabetic effect of Melicope lunu-ankenda (ML) leaves extract.

    METHODS: In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways.

    RESULTS: The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism.

    CONCLUSION: ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.

    Matched MeSH terms: Liver/drug effects; Liver/enzymology
  2. Fulltext Glycyrrhizic acid can attenuate metabolic deviations caused by a high-sucrose diet without causing water retention in male Sprague-Dawley rats
    Fernando HA, Chandramouli C, Rosli D, Lam YL, Yong ST, Yaw HP, et al.
    Nutrients, 2014 Nov 04;6(11):4856-71.
    PMID: 25375630 DOI: 10.3390/nu6114856
    Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time.
    Matched MeSH terms: Liver/drug effects; Liver/metabolism
  3. Fulltext Protective effects of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone chalcone in indomethacin-induced gastric erosive damage in rats
    Dhiyaaldeen SM, Amin ZA, Darvish PH, Mustafa IF, Jamil MM, Rouhollahi E, et al.
    BMC Vet Res, 2014;10:961.
    PMID: 25551777 DOI: 10.1186/s12917-014-0303-7
    Non-steroidal anti-inflammatory drugs (NSAIDs) can result in peptic ulcer disease (PUD) which is a common condition worldwide. The aim of this study was to evaluate the antiulcer properties of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone) (HPTP) chalcone in rats using indomethacin as ulcerogenic agent.
    Matched MeSH terms: Liver/drug effects
  4. Increased risk of insulin resistance in rat offsprings exposed prenatally to white rice
    Imam MU, Ismail M, Ooi DJ, Sarega N, Ishaka A
    Mol Nutr Food Res, 2015 Jan;59(1):180-4.
    PMID: 25329877 DOI: 10.1002/mnfr.201400396
    White rice (WR) is a major staple food for people in developing countries and it may be responsible for the growing incidence of type 2 diabetes. Nonpregnant Female Sprague Dawley rats fed with WR or brown rice (BR) for 8 weeks were mated with age-matched male rats maintained on normal pellet over the same period. Offsprings were fed normal pellet after weaning until 8 weeks postdelivery. Rats fed with WR and their offsprings showed worsened oral glucose tolerance test, lower serum adiponectin levels, and higher weights, homeostatic model assessment of insulin resistance, serum retinol binding protein-4 levels, and leptin levels, compared with the normal and BR groups, suggesting an increased risk of insulin resistance. Furthermore, transcriptional levels of genes involved in insulin signaling showed different expression patterns in the liver, muscle, and adipose tissues of mothers and offsprings in both WR and BR groups. The results propose that the cycle of WR-induced insulin resistance in offsprings due to prenatal exposure, followed by their consumption of WR later in life may contribute to diabetes incidents. These findings are worth studying further.
    Matched MeSH terms: Liver/metabolism
  5. Fulltext Comparative study of the metal accumulation in Hysterothalycium reliquens (nematode) and Paraphilometroides nemipteri (nematode) as compared with their doubly infected host, Nemipterus peronii (Notched threadfin bream)
    Mazhar R, Shazili NA, Harrison FS
    Parasitol Res, 2014 Oct;113(10):3737-43.
    PMID: 25115732 DOI: 10.1007/s00436-014-4039-x
    In February 2013, forty-seven Notched threadfin bream, the Nemipterus peronii, were sampled from the eastern coastal waters of the South China Sea. The concentration of various elements, namely cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), strontium (Sr), manganese (Mn), selenium (Se), Lead (Pb), nickel (Ni), aluminum (Al), arsenic (As), iron (Fe), and Zinc (Zn) were analyzed in the liver, muscle, and kidney organs of the host, as well as in their parasites Hysterothalycium reliquens (nematode) and the Paraphilometroides nemipteri (nematode), using inductively coupled plasma mass spectrometry (ICP-MS). The former group of parasites showed highest accumulation capacity for Cr, Cu, Fe, Mn, Se, Ni, and Zn while the latter group had high accumulation potential of As, Hg, Cd, Al, Pb, and Sr. The divergence in heavy-metal accumulation profiles of both nematodes is linked with the specificity of microhabitats, cuticle morphology, and interspecific competition. The outcome of this study indicates that both parasite models can be used for biomonitoring of metal pollution in marine ecosystems.
    Matched MeSH terms: Liver/metabolism
  6. Fulltext Engineered silybin nanoparticles educe efficient control in experimental diabetes
    Das S, Roy P, Pal R, Auddy RG, Chakraborti AS, Mukherjee A
    PLoS One, 2014;9(7):e101818.
    PMID: 24991800 DOI: 10.1371/journal.pone.0101818
    Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17 ± 0.01 µg/lit to 0.57 ± 0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.
    Matched MeSH terms: Liver/metabolism
  7. Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors
    Takhi M, Sreenivas K, Reddy CK, Munikumar M, Praveena K, Sudheer P, et al.
    Eur J Med Chem, 2014 Sep 12;84:382-94.
    PMID: 25036796 DOI: 10.1016/j.ejmech.2014.07.036
    A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.
    Matched MeSH terms: Microsomes, Liver/metabolism
  8. Fulltext Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction
    Wu LE, Meoli CC, Mangiafico SP, Fazakerley DJ, Cogger VC, Mohamad M, et al.
    Diabetes, 2014 Aug;63(8):2656-67.
    PMID: 24696450 DOI: 10.2337/db13-1665
    The vascular endothelial growth factor (VEGF) family of cytokines are important regulators of angiogenesis that have emerged as important targets for the treatment of obesity. While serum VEGF levels rise during obesity, recent studies using genetic models provide conflicting evidence as to whether VEGF prevents or accelerates metabolic dysfunction during obesity. In the current study, we sought to identify the effects of VEGF-A neutralization on parameters of glucose metabolism and insulin action in a dietary mouse model of obesity. Within only 72 h of administration of the VEGF-A-neutralizing monoclonal antibody B.20-4.1, we observed almost complete reversal of high-fat diet-induced insulin resistance principally due to improved insulin sensitivity in the liver and in adipose tissue. These effects were independent of changes in whole-body adiposity or insulin signaling. These findings show an important and unexpected role for VEGF in liver insulin resistance, opening up a potentially novel therapeutic avenue for obesity-related metabolic disease.
    Matched MeSH terms: Liver/metabolism
  9. Fulltext Triplex PCR using new primers for the detection of Toxoplasma gondii
    Rahumatullah A, Khoo BY, Noordin R
    Exp Parasitol, 2012 Jun;131(2):231-8.
    PMID: 22561042 DOI: 10.1016/j.exppara.2012.04.009
    Molecular methods are used increasingly for the detection of Toxoplasma gondii infection. This study developed a rapid, sensitive, and specific conventional triplex PCR for the detection of the B1 gene and ITS1 region of T. gondii using newly designed primers and an internal control based on the Vibrio cholerae HemM gene. The annealing temperature and concentrations of the primers, MgCl(2), and dNTPs were optimized. Two sets of primers (set 1 and 2) were tested, which contained different segments of the T. gondii B1 gene, 529 repeat region and ITS1 region. A series of sensitivity tests were performed using parasite DNA, whole parasites, and spiked human body fluids. Specificity tests were performed using DNA from common protozoa and bacteria. The newly developed assay based on set 2 primers was found to be specific and sensitive. The test was capable of detecting as little as 10 pg T. gondii DNA, 10(4) tachyzoites in spiked body fluids, and T. gondii DNA in the organ tissues of experimentally infected mice. The assay developed in this study will be useful for the laboratory detection of T. gondii infection.
    Matched MeSH terms: Liver/parasitology
  10. Levels, temporal trends, and tissue distribution of perfluorinated surfactants in freshwater fish from Asian countries
    Murakami M, Adachi N, Saha M, Morita C, Takada H
    Arch Environ Contam Toxicol, 2011 Nov;61(4):631-41.
    PMID: 21424221 DOI: 10.1007/s00244-011-9660-4
    Perfluorinated surfactants (PFSs) in Asian freshwater fish species were analyzed to investigate tissue distribution, temporal trends, extent of pollution, and level of PFS exposure through food intake. Freshwater fish species, namely carp, snakehead, and catfish, were collected in Japan, Vietnam, India, Malaysia, and Thailand, and 10 PFSs, including perfluorooctanesulfonate (PFOS) and perfluorooctanoate, were analyzed by liquid chromatography-tandem mass spectrometry. PFSs in carp in Tokyo were more concentrated in kidneys (Σ10 PFSs = 257 ± 95 ng/g wet weight [ww]) and livers (119 ± 36 ng/g ww) than in ovaries (43 ± 2 ng/g ww) and muscles (24 ± 17 ng/g ww). Concentrations of PFOS and its precursor, perfluorooctane sulfonamide, in livers of carp and in waters in Tokyo showed a dramatic decrease during the last decade, probably because of 3 M's phasing-out of the manufacture of perfluorooctanesulfonyl-fluoride-based products in 2000. In contrast, continuing contamination by long-chain perfluorocarboxylates (PFCAs) with ≥ 9 fluorinated carbons was seen in multiple media, suggesting that these compounds continue to be emitted. PFS concentrations in freshwater fish species in tropical Asian countries were generally lower than those in developed countries, such as Japan, e.g., for PFOS in muscle, Vietnam < 0.05-0.3 ng/g ww; India < 0.05-0.2 ng/g ww; Malaysia < 0.05-0.2 ng/g ww; Thailand < 0.05 ng/g ww; and Japan (Tokyo) = 5.1-22 ng/g ww. Daily intake of short-chain PFCAs with ≤ 8 fluorinated carbons from freshwater fish species in Japan was approximately one order of magnitude lower than that from drinking water, whereas daily intake of PFOS and long-chain PFCAs with ≥ 9 fluorinated carbons from freshwater fish species was comparable with or greater than that from drinking water. Because the risk posed by exposure to these compounds through intake of fish species is a matter of concern, we recommend the continued monitoring of PFS levels in Asian developing countries.
    Matched MeSH terms: Liver/metabolism
  11. A case report: metastatic choriocarcinoma to the gum
    Shafiee MN, Ismail NM, Shan LP, Kampan N, Omar MH, Dali HM
    Sex Reprod Healthc, 2011 Apr;2(2):91-2.
    PMID: 21439527 DOI: 10.1016/j.srhc.2011.02.001
    Choriocarcinoma is a rare neoplasia with a tendency of distant metastasis although highly sensitive to chemotherapy renders a good prognosis and outcome. Lungs, liver and cerebral metastasis are commonly implicated with maxillofacial region rarely involved. We illustrate a case of overwhelming metastatic choriocarcinoma to lungs, liver, brain and to the extreme of gum metastasis. Decompressive craniectomy for intracranial bleeding, multiple transfusions to correct anaemia and coagulopathy were done before high-risk-regime chemotherapy. Despite this, due to fulminant multi-organs involvement she finally succumbed to death. In conclusion, gum bleeding in choriocarcinoma may suggest metastasis and poor prognosis.
    Matched MeSH terms: Liver Neoplasms/secondary
  12. Fulltext Preparation of hippurate-zinc layered hydroxide nanohybrid and its synergistic effect with tamoxifen on HepG2 cell lines
    Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Zainal Z, Hakim MN
    Int J Nanomedicine, 2011;6:3099-111.
    PMID: 22163163 DOI: 10.2147/IJN.S24510
    A new simple preparation method for a hippurate-intercalated zinc-layered hydroxide (ZLH) nanohybrid has been established, which does not need an anion-exchange procedure to intercalate the hippurate anion into ZLH interlayers.
    Matched MeSH terms: Liver Neoplasms/drug therapy
  13. Combined use of wild-type HBV precore and high serum iron marker as a potential tool for the prediction of cirrhosis in chronic hepatitis B infection
    Chook JB, Ngeow YF, Yap SF, Tan TC, Mohamed R
    J Med Virol, 2011 Apr;83(4):594-601.
    PMID: 21328372 DOI: 10.1002/jmv.22016
    Hepatitis B virus (HBV) and high liver iron deposits have both been associated with the development of cirrhosis. Among HBV factors, genotype and mutations in the basal core promoter (BCP) and precore regions have been most frequently studied but the evidence for a positive association with cirrhosis has been inconsistent. In this study, sera from persons with chronic HBV infection with and without cirrhosis were used for whole HBV genome analysis and for the estimation of serum iron marker (serum iron or ferritin) levels. Single codon analysis showed that the precore wild-type, TGG (nt 1,895-1,897), gave the highest accuracy (77.5%) for the identification of cirrhosis compared to other codons. When TGG was analyzed together with the precore start codon wild-type, ATG (nt 1,814-1,816), the accuracy was improved to 80.0% (odds ratio=35.29; 95% confidence interval=3.87-321.93; Phi=0.629; P<0.001). When the serum iron marker was included for analysis, it was clear that a combination of a precore wild-type and high serum iron marker gave a better accuracy (90.0%) (odds ratio=107.67; 95% confidence interval=10.21-1,135.59; Phi=0.804; P<0.001) for the identification of cirrhosis than either biomarker alone. It appeared that a combined use of both these biomarkers might help to predict the development of cirrhosis in a person with chronic HBV infection, but longitudinal studies are required to test this hypothesis.
    Matched MeSH terms: Liver Cirrhosis/diagnosis*
  14. Neonatal intrahepatic cholestasis associated with citrin deficiency (NICCD): a case series of 11 Malaysian patients
    Chew HB, Ngu LH, Zabedah MY, Keng WT, Balasubramaniam S, Hanifah MJ, et al.
    J Inherit Metab Dis, 2010 Dec;33 Suppl 3:S489-95.
    PMID: 21161389 DOI: 10.1007/s10545-010-9248-6
    Citrin deficiency, aetiologically linked to mutations of SLC25A13 gene, has two clinical phenotypes, namely adult-onset type II citrullinaemia (CTLN2) and neonatal/infantile intrahepatic cholestasis, caused by citrin deficiency (NICCD). Malaysian patients with NICCD, especially of Malay and East Malaysian indigenous descent, have never been reported in the literature. We present the clinical features, biochemical findings and results of molecular analysis in 11 Malaysian children with NICCD. In this case series, all patients manifested prolonged cholestatic jaundice and elevated citrulline levels. The other more variable features included failure to thrive, bleeding diathesis, hypoproteinaemia, abnormal liver enzymes, prolonged coagulation profile, hyperammonaemia, hypergalactosaemia, multiple aminoacidaemia, elevated α-feto protein and urinary orotic acid as well as liver biopsies showing hepatitis and steatosis. DNA analysis of SLC25A13 revealed combinations of 851del4(Ex9), IVS16ins3kb and 1638ins23. Most of our patients recovered completely by the age of 22 months. However, one patient had ongoing symptoms at the time of reporting and one had died of liver failure. Since a small percentage of children with NICCD will develop CTLN2 and the mechanisms leading to this is yet to be defined, ongoing health surveillance into adulthood is essential.
    Matched MeSH terms: Liver Failure/etiology
  15. Modulation of lipid metabolism by Centella asiatica in oxidative stress rats
    Hussin M, Hamid AA, Mohamad S, Saari N, Bakar F, Dek SP
    J Food Sci, 2009 Mar;74(2):H72-8.
    PMID: 19323754 DOI: 10.1111/j.1750-3841.2009.01045.x
    A study was carried out to investigate the effects of Centella asiatica leaf on lipid metabolism of oxidative stress rats. The rats were fed 0.1% hydrogen peroxide (H(2)O(2)) with either 0.3% (w/w) C. asiatica extract, 5%C. asiatica powder (w/w), or 0.3% (w/w) alpha-tocopherol for 25 wk. Results of the study showed that C. asiatica powder significantly (P < 0.05) lowered serum low-density lipoprotein compared to that of control rats (rats fed H(2)O(2) only). At the end of the study C. asiatica-fed rats were also found to have significantly (P < 0.05) higher high-density lipoprotein and lower triglyceride level compared to rats fed only normal diet. However, cholesterol level of rats fed both C. asiatica extract and powder was found to be significantly (P < 0.05) higher compared to that of control rats. It was interesting to note that consumption of C. asiatica significantly decreased body and liver weights of the rats. Histological examinations revealed no obvious changes in all rats studied. Quantitative analysis of C. asiatica leaf revealed high concentration of total phenolic compounds, in particular, catechin, quercetin, and rutin.
    Matched MeSH terms: Liver/drug effects
  16. Incidence of risk factors for developing hyperkalemia when using ACE inhibitors in cardiovascular diseases
    Amir O, Hassan Y, Sarriff A, Awaisu A, Abd Aziz N, Ismail O
    Pharm World Sci, 2009 Jun;31(3):387-93.
    PMID: 19255869 DOI: 10.1007/s11096-009-9288-x
    STUDY OBJECTIVE: To determine the incidence of and the risk factors associated with hyperkalemia, induced by ACEI-drug interactions among cardiac patients.

    SETTING: Five medical and cardiology wards of a tertiary care center in Malaysia.

    SUBJECTS: Five hundred cardiac inpatients, who received ACEIs concomitantly with other interacting drugs.

    METHOD: This was a prospective cohort study of 500 patients with cardiovascular diseases admitted to Penang Hospital between January to August 2006, who received ACEIs concomitantly with other interacting drugs. ACEI-drug interactions of clinical significance were identified using available drug information resources. Drug Interaction Probability Scale (DIPS) was used to assess the causality of association between ACEI-drug interactions and the adverse outcome (hyperkalemia).

    MAIN OUTCOME MEASURE: Hyperkalemia as an adverse clinical outcome of the interaction was identified from laboratory investigations.

    RESULTS: Of the 489 patients included in the analysis, 48 (9.8%) had hyperkalemia thought to be associated with ACEI-drug interactions. Univariate analysis using binary logistic regression revealed that advanced age (60 years or more), and taking more than 15 medications were independent risk factors significantly associated with hyperkalemia. However, current and previous smoking history appeared to be a protective factor. Risk factors identified as predictors of hyperkalemia secondary to ACEI-drug interactions by multi-logistic regression were: advanced age (adjusted OR 2.3, CI 1.07-5.01); renal disease (adjusted OR 4.7, CI 2.37-9.39); hepatic disease (adjusted OR 5.2, CI 1.08-25.03); taking 15-20 medications (adjusted OR 4.4, CI 2.08-9.19); and taking 21-26 medications (adjusted OR 9.0, CI 1.64-49.74).

    CONCLUSION: Cardiac patients receiving ACEIs concomitantly with potentially interacting drugs are at high risk of experiencing hyperkalemia. Old age, renal disease, hepatic disease, and receiving large number of medications are factors that may significantly increase their vulnerability towards this adverse outcome; thus, frequent monitoring is advocated.

    Matched MeSH terms: Liver Diseases/complications
  17. Strategies adopted by the mudskipper Boleophthalmus boddaerti to survive sulfide exposure in normoxia or hypoxia
    Ip YK, Kuah SS, Chew SF
    Physiol Biochem Zool, 2004 Sep-Oct;77(5):824-37.
    PMID: 15547800
    The effects of sulfide on the energy metabolism of Boleophthalmus boddaerti in normoxia and hypoxia were examined. The 24-, 48-, and 96-h LC50 values of sulfide for B. boddaerti with body weight ranging from 11.6 to 14.2 g were 0.786, 0.567, and 0.467 mM, respectively. The tolerance of B. boddaerti to sulfide was not due to the presence of a sulfide-insensitive cytochrome c oxidase. There was no accumulation of lactate in the muscle and liver of specimens exposed to sulfide in normoxia. In addition, the levels of ATP, AMP, and energy charge in both the muscle and the liver were unaffected. These results indicate that B. boddaerti was able to sustain the energy supply required for its metabolic needs via mainly aerobic respiration when exposed to sulfide (up to 0.4 mM) in normoxia. Exposure of B. boddaerti simultaneously to hypoxia and 0.2 mM sulfide for 48 h resulted in decreases in the ATP levels in the muscle and liver. However, the energy charge in both tissues remained unchanged, and the level of lactate accumulated in the muscle was too low to have any major contribution to the energy budget of the fish. Our results reveal that B. boddaerti possesses inducible mechanisms to detoxify sulfide in an ample supply or a lack of O2. In normoxia, it detoxified sulfide to sulfate, sulfite, and thiosulfate. There were significant increases in the activities of sulfide oxidase in the muscle and liver of specimens exposed to sulfide, with that in the liver being >13-fold higher than that in the muscle. However, in hypoxia, sulfide oxidase activity in the liver was suppressed in response to environmental sulfide. In such conditions, there were significant increases in the activities of sulfane sulfur-forming enzyme(s) in the muscle and liver that were not observed in specimens exposed to sulfide in normoxia. Correspondingly, there were no changes in the levels of sulfate or sulfite in the muscle or liver. Instead, B. boddaerti detoxified sulfide mainly to sulfane sulfur in hypoxia. In conclusion, B. boddaerti was able to activate different mechanisms to detoxify sulfide, producing different types of detoxification products in normoxia and hypoxia.
    Matched MeSH terms: Liver/metabolism
  18. Heterologous expression of human cytochrome P450 (CYP) 2C19 in Escherichia coli and establishment of RP-HPLC method to serve as activity marker
    Pan Y, Mak JW, Ong CE
    Biomed Chromatogr, 2013 Jul;27(7):859-65.
    PMID: 23386533 DOI: 10.1002/bmc.2872
    In this study, a simple and reliable reverse-phase high-performance liquid chromatography (RP-HPLC) method was established and validated to analyze S-mephenytoin 4-hydroxylase activity of a recombinant CYP2C19 system. This system was obtained by co-expressing CYP2C19 and NADPH-CYP oxidoreductase (OxR) proteins in Escherichia coli (E. coli) cells. In addition to RP-HPLC, the expressed proteins were evaluated by immunoblotting and reduced CO difference spectral scanning. The RP-HPLC assay showed good linearity (r(2) = 1.00) with 4-hydroxymephenytoin concentration from 0.100 to 50.0 μm and the limit of detection was 5.00 × 10(-2) μm. Intraday and interday precisions determined were from 1.90 to 8.19% and from 2.20 to 14.9%, respectively. Recovery and accuracy of the assay were from 83.5 to 85.8% and from 95.0 to 105%. Enzyme kinetic parameters (Km , Vmax and Ki ) were comparable to reported values. The presence of CYP2C19 in bacterial membranes was confirmed by immunoblotting and the characteristic absorbance peak at 450 nm was determined in the reduced CO difference spectral assay. Moreover, the activity level of co-expressed OxR was found to be comparable to that of the literature. As a conclusion, the procedures described here have generated catalytically active CYP2C19 and the RP-HPLC assay developed is able to serve as CYP2C19 activity marker for pharmacokinetic drug interaction study in vitro.
    Matched MeSH terms: Microsomes, Liver/metabolism
  19. Hepatitis B: review of development from the discovery of the "Australia Antigen" to end of the twentieth Century
    Yap SF
    Malays J Pathol, 2004 Jun;26(1):1-12.
    PMID: 16190102
    "Parenteral" or "serum" hepatitis is known to have afflicted man for centuries. However, it was not until the mid-1960s that the causative agent of this infection, the hepatitis B virus, was discovered. Since then, the biology and the replication strategy of the virus, and the clinical features and the epidemiology of the hepatitis B infection have been determined. Knowledge about the virus and the infection it causes led to the development of firstly, a plasma-derived vaccine and later a recombinant vaccine for the prevention of the infection. Integration of the hepatitis B vaccine into newborn vaccination programmes on a worldwide basis represents a major step in the effort to eliminate this infectious disease and its complications. Laboratory tests are available for the diagnosis and monitoring of the disease. Therapies have been developed to halt the progress of the chronic infection in affected individuals. While these developments have resulted in a decrease of the frequency of infection in many countries, particularly those that have implemented universal immunization of newborns, the chronic infection remains a significant global problem. Worldwide, over 300 million individuals are infected and each year, an estimated 1 million persons die from chronic complications of the disease including hepatocellular carcinoma and hepatic failure. The therapies currently available result in elimination of the virus in only a relatively small proportion of subjects and carry with it serious side effects. Geopolitical, economic and other factors hinder the vision of elimination of the infection through immunization programmes. Nevertheless, work continues to clarify further the underlying pathological mechanism of the infection, the host and viral factors that promote elimination or persistence of the virus in the human host. It is hoped that such investigations will reveal viral targets for the design of newer and potentially more effective drugs to treat the infection.
    Matched MeSH terms: Liver Neoplasms/virology
  20. Fulltext High fat diet-induced inflammation and oxidative stress are attenuated by N-acetylneuraminic acid in rats
    Yida Z, Imam MU, Ismail M, Ismail N, Ideris A, Abdullah MA
    J Biomed Sci, 2015;22:96.
    PMID: 26498218 DOI: 10.1186/s12929-015-0211-6
    Serum sialic acid levels are positively correlated with coronary artery disease and inflammation. Although sialic acid is a non-specific marker, it is considered sensitive likely due to its influence in sialylation of glycoprotein structures all over the body.
    Matched MeSH terms: Liver/metabolism
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