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  1. Fulltext Origin and evolution of European community-acquired methicillin-resistant Staphylococcus aureus
    Stegger M, Wirth T, Andersen PS, Skov RL, De Grassi A, Simões PM, et al.
    mBio, 2014 Aug 26;5(5):e01044-14.
    PMID: 25161186 DOI: 10.1128/mBio.01044-14
    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations.

    IMPORTANCE: With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.

    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  2. Fulltext Discovery of New Genes Involved in Curli Production by a Uropathogenic Escherichia coli Strain from the Highly Virulent O45:K1:H7 Lineage
    Nhu NTK, Phan MD, Peters KM, Lo AW, Forde BM, Min Chong T, et al.
    mBio, 2018 08 21;9(4).
    PMID: 30131362 DOI: 10.1128/mBio.01462-18
    Curli are bacterial surface-associated amyloid fibers that bind to the dye Congo red (CR) and facilitate uropathogenic Escherichia coli (UPEC) biofilm formation and protection against host innate defenses. Here we sequenced the genome of the curli-producing UPEC pyelonephritis strain MS7163 and showed it belongs to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. MS7163 produced curli at human physiological temperature, and this correlated with biofilm growth, resistance of sessile cells to the human cationic peptide cathelicidin, and enhanced colonization of the mouse bladder. We devised a forward genetic screen using CR staining as a proxy for curli production and identified 41 genes that were required for optimal CR binding, of which 19 genes were essential for curli synthesis. Ten of these genes were novel or poorly characterized with respect to curli synthesis and included genes involved in purine de novo biosynthesis, a regulator that controls the Rcs phosphorelay system, and a novel repressor of curli production (referred to as rcpA). The involvement of these genes in curli production was confirmed by the construction of defined mutants and their complementation. The mutants did not express the curli major subunit CsgA and failed to produce curli based on CR binding. Mutation of purF (the first gene in the purine biosynthesis pathway) and rcpA also led to attenuated colonization of the mouse bladder. Overall, this work has provided new insight into the regulation of curli and the role of these amyloid fibers in UPEC biofilm formation and pathogenesis.IMPORTANCE Uropathogenic Escherichia coli (UPEC) strains are the most common cause of urinary tract infection, a disease increasingly associated with escalating antibiotic resistance. UPEC strains possess multiple surface-associated factors that enable their colonization of the urinary tract, including fimbriae, curli, and autotransporters. Curli are extracellular amyloid fibers that enhance UPEC virulence and promote biofilm formation. Here we examined the function and regulation of curli in a UPEC pyelonephritis strain belonging to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. Curli expression at human physiological temperature led to increased biofilm formation, resistance of sessile cells to the human cationic peptide LL-37, and enhanced bladder colonization. Using a comprehensive genetic screen, we identified multiple genes involved in curli production, including several that were novel or poorly characterized with respect to curli synthesis. In total, this study demonstrates an important role for curli as a UPEC virulence factor that promotes biofilm formation, resistance, and pathogenesis.
    Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology
  3. Fulltext Novel Plasmid-Mediated Colistin Resistance Gene mcr-3 in Escherichia coli
    Yin W, Li H, Shen Y, Liu Z, Wang S, Shen Z, et al.
    mBio, 2017 06 27;8(3).
    PMID: 28655818 DOI: 10.1128/mBio.00543-17
    The mobile colistin resistance gene mcr-1 has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of mcr-1, and a second mobile colistin resistance gene, mcr-2, have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene, mcr-3 The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine Escherichia colimcr-3 showed 45.0% and 47.0% nucleotide sequence identity to mcr-1 and mcr-2, respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other Enterobacteriaceae species and in 10 Aeromonas species, respectively. pWJ1 was mobilized to an E. coli recipient by conjugation and contained a plasmid backbone similar to those of other mcr-1-carrying plasmids, such as pHNSHP45-2 from the original mcr-1-harboring E. coli strain. Moreover, a truncated transposon element, TnAs2, which was characterized only in Aeromonas salmonicida, was located upstream of mcr-3 in pWJ1. This ΔTnAs2-mcr-3 element was also identified in a shotgun genome sequence of a porcine E. coli isolate from Malaysia, a human Klebsiella pneumoniae isolate from Thailand, and a human Salmonella enterica serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene mcr-3 among Enterobacteriaceae and aeromonads; the latter may act as a potential reservoir for mcr-3IMPORTANCE The emergence of the plasmid-mediated colistin resistance gene mcr-1 has attracted substantial attention worldwide. Here, we examined a colistin-resistant Escherichia coli isolate that was negative for both mcr-1 and mcr-2 and discovered a novel mobile colistin resistance gene, mcr-3 The amino acid sequence of MCR-3 aligned closely with phosphoethanolamine transferases from Enterobacteriaceae and Aeromonas species originating from both clinical infections and environmental samples collected in 12 countries on four continents. Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of mcr-3 between Enterobacteriaceae and Aeromonas species, the wide spread of mcr-3 may be largely underestimated. As colistin has been and still is widely used in veterinary medicine and used at increasing frequencies in human medicine, the continuous monitoring of mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is imperative for understanding and tackling the dissemination of mcr genes in both the agricultural and health care sectors.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology*; Colistin/pharmacology*
  4. Fulltext The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci
    D'Aeth JC, van der Linden MP, McGee L, de Lencastre H, Turner P, Song JH, et al.
    Elife, 2021 Jul 14;10.
    PMID: 34259624 DOI: 10.7554/eLife.67113
    Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly sampled Tn1207.1-type insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence, selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology*; Macrolides/pharmacology
  5. Fertilization, hatching, and embryogenesis of diploid and triploid eggs of Anabas testudineus (Bloch, 1792)
    Hassan A, Okomoda VT, Sanusi FAB
    Zygote, 2018 Oct;26(5):343-349.
    PMID: 30296962 DOI: 10.1017/S0967199418000187
    SummaryThis study investigated the breeding parameters and embryogenic development of diploid and heat shock-induced triploid eggs of Anabas testudineus (Bloch, 1792). To this effect, broodstocks of A. testudineus were induced to spawn using the Ovaprim® hormone. After fertilization, the eggs were divided into two groups and one portion heat shocked at 41°C (for 3 min), at approximately 4 min after fertilization. Results of fertilization, hatchability, as well as the sequence and timing of embryogenic development were collated from three breeding trials. Fertilization percentages were similar in both treatments (≈90%) while hatchability was higher in the diploid eggs (79.56%) than the triploid induced eggs (50.04%). Both treatments had the same sequence of embryogenetic stages; however, the timing of development was significantly delayed in the triploids (i.e. beyond the 2-cell stages) as compared with the observations in the control group (diploid eggs). Consequently, hatching time was 5 h faster in the diploid eggs [i.e. 18 hours post fertilization (hpf)] compared with the triploid induced eggs (23 hpf). The most critical stage of embryonic development in which mass mortality occurred in the different treatments was the somite stage. The status of triploid hatchlings was affirmed using erythrocyte morphology in 2-month-old fingerlings.
    Matched MeSH terms: Domperidone/pharmacology; Gonadotropin-Releasing Hormone/pharmacology
  6. Public Knowledge and Attitudes Regarding the Use of Antibiotics and Resistance: Findings from a Cross-Sectional Study Among Palestinian Adults
    Abu Taha A, Abu-Zaydeh AH, Ardah RA, Al-Jabi SW, Sweileh WM, Awang R, et al.
    Zoonoses Public Health, 2016 09;63(6):449-57.
    PMID: 26752329 DOI: 10.1111/zph.12249
    Antibiotics are considered to be among the most commonly sold drug classes in Palestine. Resistance to antibiotics has increased for reasons relating to the use and misuse of antibiotics. The aim of this study was to evaluate the knowledge, and attitudes regarding antibiotic use and awareness about resistance among adults visiting the emergency departments at hospitals in North Palestine. A self-administered cross-sectional questionnaire survey involving participants aged 18 or over was conducted from June 2012 to February 2013. Adults who visited the emergency departments at hospitals in North Palestine were included. Demographic characteristics, knowledge and attitudes towards antibiotic use were included in the questionnaire. Poor and good knowledge were defined as a total knowledge score of 0-7 and 8-15 of 15 questions, respectively. Attitude scores of 0-3 and 4-7 of 7 questions were considered poor and good, respectively. A total of 375 questionnaires were included in the study. A response rate of 83.3% was attained. About 55.0% of the participants had a good knowledge and 56.5% had a good attitude towards rational antibiotic use. A significant positive correlation was shown between participants' knowledge scores and participants' attitude scores towards antibiotic use (R = 0.344, P = 0.001. Participants with a high family income were more likely to be aware of appropriate antibiotic use than participants with a low family income (P-value <0.001). Participants with a higher educational level (university) had a good attitude towards rational antibiotic use than those with a lower education level (P-value <0.001). This study has documented important knowledge and attitude gaps in antibiotic use. These findings will help health policymakers in Palestine to implement intervention programmes to rationalize antibiotic use. Continuing medical education, professional development and training workshops for healthcare professionals regarding rational use of antibiotics and health risks associated with the spread of antibiotic resistance are needed. In addition, minimizing non-prescription use of antibiotics and increasing the public awareness about the health and economic hazards of antibiotic resistance are also required.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology*
  7. Antibiotic resistance through the lens of One Health: A study from an urban and a rural area in Sri Lanka
    Gunasekara YD, Kottawatta SA, Nisansala T, Wijewickrama IJB, Basnayake YI, Silva-Fletcher A, et al.
    Zoonoses Public Health, 2024 Feb;71(1):84-97.
    PMID: 37880923 DOI: 10.1111/zph.13087
    This study aimed to investigate and compare the proportion of AMR Escherichia coli (E. coli) between urban (Dompe in the Western province) and rural (Dambana in the Sabaragamuwa province) areas in Sri Lanka. The overall hypothesis of the study is that there is a difference in the proportion of AMR E. coli between the urban and the rural areas. Faecal samples were collected from healthy humans (n = 109), dairy animals (n = 103), poultry (n = 35), wild mammals (n = 81), wild birds (n = 76), soil (n = 80) and water (n = 80) from both areas. A total of 908 E. coli isolates were tested for susceptibility to 12 antimicrobials. Overall, E. coli isolated from urban area was significantly more likely to be resistant than those isolated from rural area. The human domain of the area had a significantly higher prevalence of AMR E. coli, but it was not significantly different in urban (98%) and rural (97%) areas. AMR E. coli isolated from dairy animals, wild animals and water was significantly higher in the urban area compared with the rural area. There was no significant difference in the proportion of multidrug resistance (MDR) E. coli isolated from humans, wild animals and water between the two study sites. Resistant isolates found from water and wild animals suggest contamination of the environment. A multi-sectorial One Health approach is urgently needed to control the spread of AMR and prevent the occurrences of AMR in Sri Lanka.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  8. DPPH free radical scavenger components from the fruits of Alpinia rafflesiana Wall. ex. Bak. (Zingiberaceae)
    Mohamad H, Abas F, Permana D, Lajis NH, Ali AM, Sukari MA, et al.
    Z Naturforsch C J Biosci, 2005 1 26;59(11-12):811-5.
    PMID: 15666539
    The methanol extract of the dried ripe fruits of Alpinia rafflesiana was investigated for its DPPH free radical scavenger constituents. 2',3',4',6'-Tetrahydroxychalcone (7), which has never been isolated from natural sources was found to be most active as a DPPH free radical scavenger with the IC50 value of 55 microM. Other known compounds isolated from this species include 5,6-dehydrokawain (1), flavokawin B (2). 1,7-diphenyl-5-hydroxy-6-hepten-3-one (3), (-)-pinocembrin (4), cardamonin (5) and (-)-pinostrobin (6). The DPPH free radical scavenger compounds were detected using TLC autographic analysis. The percentage inhibition of DPPH free radical scavenging activity was measured on isolates (5-7) using colorimetric analysis.
    Matched MeSH terms: Biphenyl Compounds/pharmacology*; Hydrazines/pharmacology*; Free Radical Scavengers/pharmacology*
  9. Antifungal garcinia acid esters from the fruits of Garcinia atroviridis
    Mackeen MM, Ali AM, Lajis NH, Kawazu K, Kikuzaki H, Nakatani N
    Z Naturforsch C J Biosci, 2002 6 18;57(3-4):291-5.
    PMID: 12064729
    Two new garcinia acid derivatives, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2-hydroxy-3-propanolide and 1',1"-dibutyl methyl hydroxycitrate, were isolated from the fruits of Garcinia atroviridis guided by TLC bioautography against the fungus Cladosporium herbarum. The structures of these compounds were established by spectral analysis. The former compound represents a unique beta-lactone structure and the latter compound is most likely an artefact of garcinia acid (= hydroxycitric acid). Both compounds showed selective antifungal activity comparable to that of cycloheximide (MID: 0.5 microg/spot) only against C herbarum at the MIDs of 0.4 and 0.8 microg/spot but were inactive against bacteria (Bacillus subtilis, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli), other fungi (Alternaria sp., Fusarium moniliforme and Aspergillus ochraceous) including the yeast Candida albicans.
    Matched MeSH terms: Antifungal Agents/pharmacology; Citrates/pharmacology; Cycloheximide/pharmacology; Lactones/pharmacology
  10. Biological evaluation of curcumin and related diarylheptanoids
    Abas F, Hui LS, Ahmad S, Stanslas J, Israf DA, Shaari K, et al.
    Z Naturforsch C J Biosci, 2006 12 2;61(9-10):625-31.
    PMID: 17137104
    Nine derivatives of three natural diarylheptanoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin, were prepared. Their antioxidant, free radical scavenging, nitric oxide (NO) inhibitory and cytotoxic activities were evaluated and compared with those of the respective natural compounds. Curcumin (1), demethoxycurcumin (2), demethyldemethoxy-curcumin (C3), diacetyldemethoxycurcumin (AC2) and triacetyldemethylcurcumin (AC5) exhibited higher antioxidant activity than quercetin while products from demethylation of 1 and 2 exhibited higher free radical scavenging activity. Compounds AC2 and AC5 were found to be most active in inhibiting breast cancer cells (MCF-7) proliferation with IC50 values of 6.7 and 3.6 microM, respectively. The activity of AC2 is almost doubled and of AC5 almost tripled as compared to curcumin. Their selectivity towards different cell lines is also more noticeable. Compounds AC2 and AC5 also showed increased activity against a human prostate cancer cell line (DU-145) and non-small lung cancer cell line (NCI-H460) with IC50 values of 20.4, 16.3 and 18.3, 10.7 microM, respectively.
    Matched MeSH terms: Antioxidants/pharmacology
  11. Chemical composition and anticholinesterase inhibitory activity of Pavetta graciliflora Wall. ex Ridl. essential oil
    Salleh WMNHW, Khamis S
    Z Naturforsch C J Biosci, 2020 Nov 26;75(11-12):467-471.
    PMID: 32469335 DOI: 10.1515/znc-2020-0075
    Chemical composition and anticholinesterase activity of the essential oil of Pavetta graciliflora Wall. ex Ridl. (Rubiaceae) was examined for the first time. The essential oil was obtained by hydrodistillation and was fully characterized by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). A total of 20 components were identified in the essential oil, which made up 92.85% of the total oil. The essential oil is composed mainly of β-caryophyllene (42.52%), caryophyllene oxide (25.33%), β-pinene (8.67%), and α-pinene (6.52%). The essential oil showed weak inhibitory activity against acetylcholinesterase (AChE) (I%: 62.5%) and butyrylcholinesterase (BChE) (I%: 65.4%) assays. Our findings were shown to be very useful for the characterization, pharmaceutical, and therapeutic applications of the essential oil from P. graciliflora.
    Matched MeSH terms: Antioxidants/pharmacology; Cholinesterase Inhibitors/pharmacology*; Oils, Volatile/pharmacology
  12. High Melatonin Conditions by Constant Darkness and High Temperature Differently Affect Melatonin Receptor mt1 and TREK Channel trek2a in the Brain of Zebrafish
    Loganathan K, Moriya S, Parhar IS
    Zebrafish, 2018 10;15(5):473-483.
    PMID: 30102584 DOI: 10.1089/zeb.2018.1594
    Ambient light and temperature affect reproductive function by regulating kisspeptin and gonadotrophin-releasing hormone (GnRH) in vertebrates. Melatonin and melatonin receptors, as well as the two-pore domain K+ channel-related K+ (TREK) channels, are affected by light and/or temperature; therefore, these molecules could modulate kisspeptin and GnRH against ambient light and temperature. In this study, we investigated the effect of light and temperature, which affect melatonin levels in gene expression levels of TREK channels, kisspeptin, and GnRH. We first investigated the effects of different light and temperature conditions on brain melatonin concentrations by ELISA. Fish were exposed to either constant darkness, constant light, high temperature (35°C), or low temperature (20°C) for 72 h. Brain melatonin levels were significantly high under constant darkness and high temperature. We further investigated the effects of high brain melatonin levels by constant darkness and high temperature on gene expression levels of melatonin receptors (mt1, mt2, and mel1c), TREK channels (trek1b, trek2a, and trek2b), gnrh3, and kiss2 in the adult zebrafish brain by real-time polymerase chain reaction. Fish were exposed to constant darkness or elevated temperatures (35°C) for 72 h. trek2a, kiss2, and gnrh3 levels were increased under constant darkness. High temperature decreased gene expression levels of mt1, mt2, mel1c, and gnrh3 in the preoptic area, whereas other genes remained unchanged. Melatonin receptors, TREK channels, gnrh3, and kiss2 responded differently under high melatonin conditions. The melatonin receptors and the TREK channels could play roles in the regulation of reproduction by environmental cues, especially ambient light and temperature.
    Matched MeSH terms: Antioxidants/pharmacology; Melatonin/pharmacology*
  13. Fulltext Induction of apoptosis in yeast by L-amino acid oxidase from the Malayan pit viper Calloselasma rhodostoma
    Ande SR, Fussi H, Knauer H, Murkovic M, Ghisla S, Fröhlich KU, et al.
    Yeast, 2008 May;25(5):349-57.
    PMID: 18437704 DOI: 10.1002/yea.1592
    Here we report for the first time that L-amino acid oxidase (LAAO), a major component of snake venom, induces apoptosis in yeast. The causative agent for induction of apoptosis has been shown to be hydrogen peroxide, produced by the enzymatic activity of LAAO. However, the addition of catalase, a specific hydrogen peroxide scavenger, does not prevent cell demise completely. Intriguingly, depletion of leucine from the medium by LAAO and the interaction of LAAO with yeast cells are shown to be the major factors responsible for cell demise in the presence of catalase.
    Matched MeSH terms: Hydrogen Peroxide/pharmacology; L-Amino Acid Oxidase/pharmacology*
  14. Special focus on the role of α(1D)-adrenoreceptors in the assessment of renal tubular sodium re-absorptive responses in spontaneously hypertensive rats subjected to high sodium diet
    Kazi RN, Sattar MA, Abdullah NA, Khan MA, Rathore HA, Abdulla MH, et al.
    Yakugaku Zasshi, 2011 Mar;131(3):431-6.
    PMID: 21372540
    α(1D)-adrenoceptors are involved in the genesis/maintenance of hypertension in spontaneously hypertensive rats (SHR). This study aims to investigate the role of α(1D)-adrenoceptors in the antinatriuretic and antidiuretic responses in SHR subjected to high sodium (SHRHNa) and normal sodium (SHRNNa) intake for six weeks. Renal inulin clearance study was performed in which the antinatriuretic and antidiuretic responses to phenylephrine were examined in the presence and absence of α(₁D)-adrenoceptors blocker BMY7378. Data, mean±S.E.M. were subjected to ANOVA with significance at p<0.05. Results show that feeding SHR for six weeks with high salt did not cause any change in blood pressure. SHRHNa had higher (all p<0.05) urine flow rate (UFR), fractional and absolute excretion of sodium (FE(Na) and U(Na)V) compared to SHRNNa. Phenylephrine infusion produced significant reduction in UFR, FE(Na) and U(Na)V in both SHRHNa and SHRNNa. The antidiuretic and antinatriuretic responses to phenylephrine in both groups were attenuated in the presence of BMY7378. Moreover, the antidiuretic and antinatriuretic responses to phenylephrine and BMY7378 were independent on any significant changes in renal and glomerular hemodynamics in both groups. Thus we conclude that high sodium intake did not bring any further increase in blood pressure of SHR, however, it results in exaggerated natriuresis and diuresis in SHRHNa. Irrespective of dietary sodium changes, α₁-adrenoceptors are involved in mediating the antinatriuretic and antidiuretic responses to phenylephrine in SHR. Further, high sodium intake did not significantly influence the functionality of α(₁D)-adrenoceptors in mediating the adrenergically induced antinatriuresis and antidiuresis.
    Matched MeSH terms: Phenylephrine/pharmacology
  15. Fulltext Caprine pancreatic islet xenotransplantation into diabetic immunosuppressed BALB/c mice
    Hani H, Allaudin ZN, Mohd-Lila MA, Ibrahim TA, Othman AM
    Xenotransplantation, 2014 Mar-Apr;21(2):174-82.
    PMID: 24645790 DOI: 10.1111/xen.12087
    BACKGROUND: Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use of caprine (goat) islet cells as xenogeneic grafts in the treatment for diabetes in a mouse model.
    METHODS: Caprine pancreases were harvested and transported to the laboratory under conditions optimized to prevent ischemia. Islets were isolated, purified, and tested for functionality. Caprine islets (2000 islet equivalent) were transplanted beneath the kidney capsules of diabetic BALB/c mice under thalidomide-induced immunosuppression. Blood glucose and insulin levels of grafted mice were evaluated by glucometer and enzyme-linked immunosorbent assay kit, respectively. The functionality and quality of caprine pancreatic islet grafts were assessed by intraperitoneal glucose tolerance tests.
    RESULTS: The viability of purified islet cells exceeded 90%. Recipient mice exhibited normoglycemia (<11 mM glucose) for 30 days. In addition, weight gain negatively correlated with blood glucose level. The findings verified diabetes reversal in caprine islet recipient mice. A significant drop in non-fasting blood glucose level (from 23.3 ± 5.4 to 8.04 ± 0.44 mM) and simultaneous increase in serum insulin level (from 0.01 ± 0.001 to 0.56 ± 0.17 μg/l) and body weights (from 23.64 ± 0.31 to 25.85 ± 0.34 g) were observed (P < 0.05). Immunohistochemical analysis verified insulin production in the transplanted islets.
    CONCLUSIONS: Purified caprine islets were demonstrated to successfully sustain viability and functionality for controlling blood glucose levels in an immunosuppressed mouse model of diabetes. These results suggest the use of caprine islets as an addition to the supply of xenogeneic islets for diabetes research.
    KEYWORDS: caprine islets; streptozotocin‐injected mice; type 1 diabetes; xenotransplantation
    Matched MeSH terms: Immunosuppressive Agents/pharmacology*
  16. Improvement of isolated caprine islet survival and functionality in vitro by enhancing of PDX1 gene expression
    Hani H, Allaudin ZN, Mohd-Lila MA, Sarsaifi K, Rasouli M, Tam YJ, et al.
    Xenotransplantation, 2017 05;24(3).
    PMID: 28397308 DOI: 10.1111/xen.12302
    BACKGROUND: Dead islets replaced with viable islets are a promising offer to restore normal insulin production to a person with diabetes. The main reason for establishing a new islet source for transplantation is the insufficiency of human donor pancreas while using xenogeneic islets perhaps assists this problem. The expression of PDX1 is essential for the pancreas expansion. In mature β-cells, PDX1 has several critical roles such as glucose sensing, insulin synthesis, and insulin secretion. In this study, we aimed to evaluate the expression of pancreatic duodenal homeobox-1 (PDX1) in treated caprine islets in culture and to assess the protective effects of antioxidant factors on the PDX1 gene in cultured caprine islets.

    MATERIALS AND METHODS: Purified islets were treated with serum-free, serum, IBMX, tocopherol, or IBMX and tocopherol media. Quantitative polymerase chain reaction and Western blotting were carried out to compare the expression levels of PDX1 in treated purified islets cultured with different media.

    RESULTS: Islets treated with IBMX/tocopherol exhibited the highest fold change in the relative expression of PDX1 on day 5 post-treatment (relative expression: 6.80±2.08), whereas serum-treated islets showed the lowest fold changes in PDX1 expression on day 5 post-treatment (0.67±0.36), as compared with the expression on day 1 post-treatment. Insulin production and viability tests of purified islets showed superiority of islet at supplemented serum-free media with IBMX/tocopherol compared to other cultures (53.875%±1.59%).

    CONCLUSIONS: Our results indicated that supplemented serum-free medium with tocopherol and IBMX enhances viability and PDX1 gene expression compared to serum-added and serum-free media.

    Matched MeSH terms: Antioxidants/pharmacology; 1-Methyl-3-isobutylxanthine/pharmacology; Tocopherols/pharmacology
  17. In vitro modulation of naturally occurring flavonoids on cytochrome P450 2A6 (CYP2A6) activity
    Tiong KH, Yiap BC, Tan EL, Ismail R, Ong CE
    Xenobiotica, 2010 Jul;40(7):458-66.
    PMID: 20402563 DOI: 10.3109/00498251003786749
    1. The effect of flavonoids on coumarin 7-hydroxylation, an activity marker of an important human liver cytochrome P450 isoform, cytochrome P450 2A6 (CYP2A6), was investigated in this study. 2. Coumarin 7-hydroxylase activity was measured fluorometrically in reaction mixtures containing cDNA-expressed CYP2A6, nicotinamide adenine dinucleotide phosphate generating system and 10 uM coumarin, at various concentrations of flavonoids. 3. Among the 23 compounds tested, most of the active members were from flavonol group of hydroxylated flavonoids, with myricetin being the most potent inhibitor followed by quercetin, galangin, and kaempferol. 4. Further exploration of the inhibition mechanism of these compounds revealed that myricetin, galangin, and kaempferol exhibited mixed-type of inhibition pattern while quercetin was observed to exhibit competitive mode of inhibition. 5. Structure-function analyses revealed that degree of inhibition was closely related to the number and location of hydroxyl groups, glycosylation of the free hydroxyl groups, degree of saturation of the flavane nucleus as well as the presence of the alkoxylated function.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology; Flavonoids/pharmacology
  18. Isolation and identification of a new intracellular antimicrobial peptide produced by Paenibacillus alvei AN5
    Alkotaini B, Anuar N, Kadhum AA, Sani AA
    World J Microbiol Biotechnol, 2014 Apr;30(4):1377-85.
    PMID: 24272828 DOI: 10.1007/s11274-013-1558-z
    A wild-type, Gram-positive, rod-shaped, endospore-forming and motile bacteria has been isolated from palm oil mill sludge in Malaysia. Molecular identification using 16S rRNA gene sequence analysis indicated that the bacteria belonged to genus Paenibacillus. With 97 % similarity to P. alvei (AUG6), the isolate was designated as P. alvei AN5. An antimicrobial compound was extracted from P. alvei AN5-pelleted cells using 95 % methanol and was then lyophilized. Precipitates were re-suspended in phosphate buffered saline (PBS), producing an antimicrobial crude extract (ACE). The ACE showed antimicrobial activity against Salmonella enteritidis ATCC 13076, Escherichia coli ATCC 29522, Bacillus cereus ATCC 14579 and Lactobacillus plantarum ATCC 8014. By using SP-Sepharose cation exchange chromatography, Sephadex G-25 gel filtration and Tricine SDS-PAGE, the ACE was purified, which produced a ~2-kDa active band. SDS-PAGE and infrared (IR) spectroscopy indicated the proteinaceous nature of the antimicrobial compound in the ACE, and liquid chromatography electrospray ionization mass spectroscopy and de novo sequencing using an automatic, Q-TOF premier system detected a peptide with the amino acid sequence F-C-K-S-L-P-L-P-L-S-V-K (1,330.7789 Da). This novel peptide was designated as AN5-2. The antimicrobial peptide exhibited stability from pH 3 to 12 and maintained its activity after being heated to 90 °C. It also remained active after incubation with denaturants (urea, SDS and EDTA).
    Matched MeSH terms: Antimicrobial Cationic Peptides/pharmacology
  19. Antibiotic resistance and molecular typing among cockle (Anadara granosa) strains of Vibrio parahaemolyticus by polymerase chain reaction (PCR)-based analysis
    Sahilah AM, Laila RA, Sallehuddin HM, Osman H, Aminah A, Ahmad Azuhairi A
    World J Microbiol Biotechnol, 2014 Feb;30(2):649-59.
    PMID: 24068534 DOI: 10.1007/s11274-013-1494-y
    Genomic DNA of Vibrio parahaemolyticus were characterized by antibiotic resistance, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis. These isolates originated from 3 distantly locations of Selangor, Negeri Sembilan and Melaka (East coastal areas), Malaysia. A total of 44 (n = 44) of tentatively V. parahaemolyticus were also examined for the presence of toxR, tdh and trh gene. Of 44 isolates, 37 were positive towards toxR gene; while, none were positive to tdh and trh gene. Antibiotic resistance analysis showed the V. parahaemolyticus isolates were highly resistant to bacitracin (92%, 34/37) and penicillin (89%, 33/37) followed by resistance towards ampicillin (68%, 25/37), cefuroxime (38%, 14/37), amikacin (6%, 2/37) and ceftazidime (14%, 5/37). None of the V. parahaemolyticus isolates were resistant towards chloramphenicol, ciprofloxacin, ceftriaxone, enrofloxacin, norfloxacin, streptomycin and vancomycin. Antibiogram patterns exhibited, 9 patterns and phenotypically less heterogenous when compared to PCR-based techniques using ERIC- and RAPD-PCR. The results of the ERIC- and RAPD-PCR were analyzed using GelCompare software. ERIC-PCR with primers ERIC1R and ERIC2 discriminated the V. parahaemolyticus isolates into 6 clusters and 21 single isolates at a similarity level of 80%. While, RAPD-PCR with primer Gen8 discriminated the V. parahaemolyticus isolates into 11 clusters and 10 single isolates and Gen9 into 8 clusters and 16 single isolates at the same similarity level examined. Results in the presence study demonstrated combination of phenotypically and genotypically methods show a wide heterogeneity among cockle isolates of V. parahaemolyticus.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  20. Anti-amoebic properties of a Malaysian marine sponge Aaptos sp. on Acanthamoeba castellanii
    Nakisah MA, Ida Muryany MY, Fatimah H, Nor Fadilah R, Zalilawati MR, Khamsah S, et al.
    World J Microbiol Biotechnol, 2012 Mar;28(3):1237-44.
    PMID: 22805843 DOI: 10.1007/s11274-011-0927-8
    Crude methanol extracts of a marine sponge, Aaptos aaptos, collected from three different localities namely Kapas, Perhentian and Redang Islands, Terengganu, Malaysia, were tested in vitro on a pathogenic Acanthamoeba castellanii (IMR isolate) to examine their anti-amoebic potential. The examination of anti-Acanthamoebic activity of the extracts was conducted in 24 well plates for 72 h at 30 °C. All extracts possessed anti-amoebic activity with their IC(50) values ranging from 0.615 to 0.876 mg/mL. The effect of the methanol extracts on the surface morphology of A. castellanii was analysed under scanning electron microscopy. The ability of the extracts to disrupt the amoeba cell membrane was indicated by extensive cell's blebbing, changes in the surface morphology, reduced in cell size and with cystic appearance of extract-treated Acanthamoeba. Number of acanthapodia and food cup was also reduced in this Acanthamoeba. Morphological criteria of apoptosis in Acanthamoeba following treatment with the sponge's extracts was determined by acridine orange-propidium iodide staining and observed by fluorescence microscopy. By this technique, apoptotic and necrotic cells can be visualized and quantified. The genotoxic potential of the methanol extracts was performed by the alkaline comet assay. All methanol extracts used were significantly induced DNA damage compared to untreated Acanthamoeba by having high percentage of scores 1, 2, and 3 of the DNA damage. Results from cytotoxicity and genotoxicity studies carried out in the present study suggest that all methanol extracts of A. aaptos have anti-amoebic properties against A. castellanii.
    Matched MeSH terms: Antiprotozoal Agents/pharmacology*
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