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Muthu Dharmasena, Xiuping Jiang
This study was to optimize the detection methods for Clostridium difficile from the animal manure-based composts. Both autoclaved and unautoclaved dairy composts were inoculated with a 12-h old suspension of a non-toxigenic C. difficile strain (ATCC 43593) and then plated on selected agar for vegetative cells and endospores. Six types of enrichment broths supplemented with taurocholate and L-cysteine were assessed for detecting a low level of artificially inoculated C. difficile (ca. 5 spores/g) from dairy composts...
March 5, 2018: Anaerobe
Majda Biasizzo, Stanka Vadnjal, Urska Henigman, Manja Krizman, Andrej Kirbis, Urska Jamnikar-Ciglenecki
There is no recommended protocol for detecting and isolating Clostridium difficile present in food samples. Here, we have evaluated the recovery of C. difficile in meat samples after incubating them in various enrichment broths. The media were as follows: cycloserine-cefoxitin fructose broth supplemented with taurocholic acid, d-cycloserine, cefoxitin, and lysozyme; cycloserine-cefoxitin mannitol broth with taurocholate and lysozyme; and cycloserine-cefoxitin fructose broth supplemented with taurocholic acid, C...
March 8, 2018: Journal of Food Protection
Marta Portero-Tresserra, Margarita Martí-Nicolovius, Mireia Tarrés-Gatius, Ana Candalija, Gemma Guillazo-Blanch, Anna Vale-Martínez
RATIONALE: Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. OBJECTIVES AND METHODS: The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats...
February 28, 2018: Psychopharmacology
Jun An, Xuejuan Bai, Mengqiu Gao, Naihui Chu, Hairong Huang, Hongyin Xu, Xiuping Zhang, Baoxia Li, Cailiu Huang, Haixia Cai, Fengqin Zhang, Yu Pang, Liang Li
OBJECTIVE: Our objective was to describe trends in anti-tuberculosis (TB) drug prescribing of inpatients from 2011 to 2015 in a National TB Hospital. METHODS: We carried out this study in March 2016, which retrospectively reviewed the medical records of all inpatients diagnosed as tuberculosis between 2011 and 2015. We recorded the medication used for the treatment of TB during the inpatient period. RESULTS: A total of 11465 inpatients from Beijing Chest Hospital were enrolled in this analysis...
February 21, 2018: Journal of Global Antimicrobial Resistance
Emiliano Merlo, Amy L Milton, Barry J Everitt
Fully consolidated fear memories can be maintained or inhibited by retrieval-dependent mechanisms depending on the degree of re-exposure to fear cues. Short exposures promote memory maintenance through reconsolidation and long exposures promote inhibition through extinction. Little is known about the neural mechanisms by which increasing cue exposure overrides reconsolidation and instead triggers extinction. Using auditory fear conditioning in male rats, we analysed the role of a molecular mechanism common to reconsolidation and extinction of fear, ERK1/2 activation within the basolateral amygdala (BLA), after intermediate CS exposure events...
February 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Y-M Fan, S-P Ding, Z-J Bao, L-M Wu, L-B Zhen, Q Xia, M Zhu
OBJECTIVE: To examine the clinical outcomes and associated prognostic factors among patients with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: This retrospective study involved 243 patients with MDR-TB. All patients received standard regimens containing para-amino salicylic acid (PAS) and/or cycloserine (CS). The demographic, social and clinical characteristics of patients were recorded and the patients were followed up for 24 months. RESULTS: Treatment success was closely associated with young age, non-farming occupations, shorter history or smoking, normal urine results, initial MDR-TB treatment regimen, increased haemoglobin, direct bilirubin, uric acid and thyroid stimulating hormone (TSH) levels, and lower white blood cell, neutrophil and blood platelet counts (all P < 0...
March 1, 2018: International Journal of Tuberculosis and Lung Disease
Ioline D Henter, Rafael Teixeira de Sousa, Carlos A Zarate
Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies...
February 20, 2018: Harvard Review of Psychiatry
Agibothu Kupparam Hemanth Kumar, Alok Kumar, Thiruvengadam Kannan, Rakesh Bhatia, Dipti Agarwal, Santosh Kumar, Rajeshwar Dayal, Sheo Pratap Singh, Geetha Ramachandran
We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH) and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR TB) being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR TB at the Sarojini Naidu Medical College, Agra, India who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Marcella L Woud, Simon E Blackwell, Susann Steudte-Schmiedgen, Michael Browning, Emily A Holmes, Catherine J Harmer, Jürgen Margraf, Andrea Reinecke
The partial N-methyl-D-aspartate receptor agonist d-cycloserine may enhance psychological therapies. However, its exact mechanism of action is still being investigated. Cognitive bias modification techniques allow isolation of cognitive processes and thus investigation of how they may be affected by d-cycloserine. We used a cognitive bias modification paradigm targeting appraisals of a stressful event, Cognitive Bias Modification-Appraisal, to investigate whether d-cycloserine enhanced the modification of appraisal, and whether it caused greater reduction in indices of psychopathology...
February 1, 2018: Journal of Psychopharmacology
Yong Wang, Yahui Liu, Jianshuai Jiang, Hanbin Cui
The existence of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) is regarded as the cause of tumor formation and recurrence. Matrine has been reported to exhibit antitumor effects in cancer cells. In the present study, a preliminary study was performed on the mechanisms of matrine on hepatocellular carcinoma (HCC) stem-like cells. The HCC SMMC-7721 cell line was cultured in tumor stem cell-specific medium to form spheres, and different concentrations (1, 2 and 5 mg/kg) of cisplatin were then used in order to purify the most drug-resistant cells, which were used as CSLCs...
February 2018: Oncology Letters
Gabrielle King, Bronwyn M Graham, Rick Richardson
The major weakness of psychological and pharmacological interventions for anxiety disorders is that the fear often returns. We examined whether DCS, which has attracted considerable attention as a potential pharmacological adjunct to therapy, reduces relapse, and whether individual differences in the rate of extinction modulates its effectiveness in reducing relapse. Experimentally-naïve adult male rats received pairings of a white noise CS with a shock US, extinction to a criterion immediately followed by an injection of DCS or Saline, and then were tested for relapse of fear (renewal, spontaneous recovery, or reinstatement; in four separate experiments)...
February 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Joseph T Coyle, Darrick T Balu
The N-methyl-d-aspartate receptor (NMDAR) is unique in requiring two agonists to bind simultaneously to open its cation channel: the neurotransmitter, glutamate, and the coagonists, glycine, or d-serine. The Snyder laboratory was the first to clone serine racemase (SR), the enzyme that synthesizes d-serine, and to localize it immunocytochemically. Our laboratory has focused on the role of d-serine in brain disorders. Silencing the expression of SR, a risk gene for schizophrenia (SCZ), in mice (SR-/-), results in a phenotype that closely resembles SCZ including: cortical atrophy, reduced dendritic spine density and complexity, downregulation of parvalbumin-positive cortical GABAergic neurons, and cognitive impairments...
2018: Advances in Pharmacology
Qi Deng, Jianzhou Meng, Yan Guan, Yishuang Liu, Chunling Xiao
The generation of conditional mutants has been an effective approach to studying bacteria and validating drug targets, and mutants of Mycobacteria are no exception. However unlike other bacteria, there is still a paucity of available tools for Mycobacteria. We constructed a new plasmid containing tetracycline-repressive expression system (TetRr1.7) and Xer Site-Specific recombinase system to generate label-free controllable expression strains. The plasmid was subsequently used to construct a strain of M. tuberculosis expressing the only copy of D-alanine:D-alanine ligase under the control of the tetracycline-repressive promoter...
February 1, 2018: AMB Express
Elisa S Na, Héctor De Jesús-Cortés, Arlene Martinez-Rivera, Zeeba D Kabir, Jieqi Wang, Vijayashree Ramesh, Yasemin Onder, Anjali M Rajadhyaksha, Lisa M Monteggia, Andrew A Pieper
[This corrects the article DOI: 10.1371/journal.pone.0183026.].
2018: PloS One
Yeong-Chan Ahn, Conrad Fischer, Marco J van Belkum, John C Vederas
O-Ureidoserine racemase (DcsC) is a PLP-independent enzyme in the biosynthetic route to the antibiotic d-cycloserine. Here we present the recombinant expression and characterization of a significantly more active DcsC variant featuring an N-terminal SUMO-tag. Synthesis of enantiomeric pure inhibitors in combination with site-specific mutation of active site cysteines to serines of this enzyme offers closer insights into the mechanism of this transformation. Homology modelling with a close relative (diaminopimelate epimerase, DapF) inspired C- and N-terminal truncation of DcsC to produce a more compact yet still active enzyme variant...
January 24, 2018: Organic & Biomolecular Chemistry
Francesc Coll, Jody Phelan, Grant A Hill-Cawthorne, Mridul B Nair, Kim Mallard, Shahjahan Ali, Abdallah M Abdallah, Saad Alghamdi, Mona Alsomali, Abdallah O Ahmed, Stephanie Portelli, Yaa Oppong, Adriana Alves, Theolis Barbosa Bessa, Susana Campino, Maxine Caws, Anirvan Chatterjee, Amelia C Crampin, Keertan Dheda, Nicholas Furnham, Judith R Glynn, Louis Grandjean, Dang Minh Ha, Rumina Hasan, Zahra Hasan, Martin L Hibberd, Moses Joloba, Edward C Jones-López, Tomoshige Matsumoto, Anabela Miranda, David J Moore, Nora Mocillo, Stefan Panaiotov, Julian Parkhill, Carlos Penha, João Perdigão, Isabel Portugal, Zineb Rchiad, Jaime Robledo, Patricia Sheen, Nashwa Talaat Shesha, Frik A Sirgel, Christophe Sola, Erivelton Oliveira Sousa, Elizabeth M Streicher, Paul Van Helden, Miguel Viveiros, Robert M Warren, Ruth McNerney, Arnab Pain, Taane G Clark
To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid...
January 22, 2018: Nature Genetics
Michelle G Craske, Dirk Hermans, Bram Vervliet
Through advances in both basic and clinical scientific research, Pavlovian fear conditioning and extinction have become an exemplary translational model for understanding and treating anxiety disorders. Discoveries in associative and neurobiological mechanisms underlying extinction have informed techniques for optimizing exposure therapy that enhance the formation of inhibitory associations and their consolidation and retrieval over time and context. Strategies that enhance formation include maximizing prediction-error correction by violating expectancies, deepened extinction, occasional reinforced extinction, attentional control and removal of safety signals/behaviours...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Artun Yibar, Ece Cetin, Zafer Ata, Evren Erkose, Mustafa Tayar
This study examined the incidence of Clostridium perfringens in raw, ready-to-cook (RTC), and ready-to-eat (RTE) meat and meat-based products (N = 306) collected from restaurants, supermarkets, and butcher shops in Bursa, Turkey. In addition, we investigated the presence of the C. perfringens enterotoxin (CPE), as well as cpe genes and their source (chromosomal or plasmid borne). In this study, tryptose sulfite cycloserine (TSC) agar for classic culture isolation and API and real-time polymerase chain reaction (RT-PCR) techniques were used to identify C...
January 9, 2018: Foodborne Pathogens and Disease
Wenjing Zhang, Sihui Wan, Lizhi Chen, Xuebing Wang, Zhuo Wang, Yi Huang
A new method for the analysis of cycloserine (4-amino-3-isoxazolidinone, CYC) in rat microdialysis samples has been developed. This method consists of derivatizing the CYC with benzoyl chloride, which transforms primary amines into highly stable derivatives. An attractive feature of this method was that the derivatization reaction is straightforward and can be completed within 10 min. The formed derivative, in contrast to the non-derivatized analyte, exhibited increased chromatographic retention and decreased matrix effects resulting from the co-elution of other components using reversed-phase liquid chromatography and on-line switching...
January 4, 2018: Biomedical Chromatography: BMC
Xia Yu, Xiling Zeng, Wenhui Shi, Yanjie Hu, Wenjuan Nie, Naihui Chu, Hairong Huang
Cycloserine is recommended by the World Health Organization as a second line drug to treat multidrug-resistant tuberculosis(MDR TB), however its efficacy has never been sufficiently evaluated. To gain some insights into the value of cycloserine (Cs) for MDR TB treatment, in vitro bacteriostatic effect and patient validations were performed prospectively.The in vitro activity of Cs against 104 wild-type M. tuberculosis strains was determined, and serum Cs concentration was measured for 73 MDR TB patients 2 hours after administration...
January 8, 2018: Antimicrobial Agents and Chemotherapy
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