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antibiotic development

Jamal Chauhan, Steven Cardinale, Lei Fang, Jing Huang, Steven M Kwasny, M Ross Pennington, Kelly Basi, Robert diTargiani, Benedict R Capacio, Alexander D MacKerell, Timothy J Opperman, Steven Fletcher, Erik P H de Leeuw
Recently we described a novel di-benzene-pyrylium-indolene (BAS00127538) inhibitor of Lipid II. BAS00127538 (1-Methyl-2,4-diphenyl-6-((1E,3E)-3-(1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)pyryl-1-ium) tetrafluoroborate is the first small molecule Lipid II inhibitor and is structurally distinct from natural agents that bind Lipid II, such as vancomycin. Here, we describe the synthesis and biological evaluation of 50 new analogs of BAS00127538 designed to explore the structure-activity relationships of the scaffold...
2016: PloS One
Shiho Fujisaka, Siegfried Ussar, Clary Clish, Suzanne Devkota, Jonathan M Dreyfuss, Masaji Sakaguchi, Marion Soto, Masahiro Konishi, Samir Softic, Emrah Altindis, Ning Li, Georg Gerber, Lynn Bry, C Ronald Kahn
Interactions of diet, gut microbiota, and host genetics play important roles in the development of obesity and insulin resistance. Here, we have investigated the molecular links between gut microbiota, insulin resistance, and glucose metabolism in 3 inbred mouse strains with differing susceptibilities to metabolic syndrome using diet and antibiotic treatment. Antibiotic treatment altered intestinal microbiota, decreased tissue inflammation, improved insulin signaling in basal and stimulated states, and improved glucose metabolism in obesity- and diabetes-prone C57BL/6J mice on a high-fat diet (HFD)...
October 24, 2016: Journal of Clinical Investigation
M Fanjul, L Pérez, J Cerdá, M Zornoza, R Rojo, I Simal, M A García-Casillas, C Corona, D Peláez, E Molina, A Parente, S Rivas, J M Angulo, E De Tomás
BACKGROUND: Multiple approaches to the treatment of simple and complicated (gangrenous or perforated) appendicitis in children have been promoted. Our goal is to develop a new protocol for these patients that allows shorter hospital stays without increasing complications rates. METHODS: Prospective collected data of patients undergoing appendicitis treated according to the new protocol for a period of 7 months were reviewed. This protocol consists on antibiotic prophylaxis in all cases continued with triple antibiotic regimen in complicated appendicitis...
October 10, 2016: Cirugía Pediátrica: Organo Oficial de la Sociedad Española de Cirugía Pediátrica
C Elizabeth Oakley, Manmeet Ahuja, Wei-Wen Sun, Ruth Entwistle, Tomohiro Akashi, Junko Yaegashi, Chun-Jun Guo, Gustavo C Cerqueira, Jennifer Russo Wortman, Clay C C Wang, Yi-Ming Chiang, Berl R Oakley
Fungal secondary metabolites (SMs) are extremely important in medicine and agriculture, but regulation of their biosynthesis is incompletely understood. We have developed a genetic screen in Aspergillus nidulans for negative regulators of fungal SM gene clusters and we have used this screen to isolate mutations that upregulate transcription of the non-ribosomal peptide synthetase gene required for nidulanin A biosynthesis. Several of these mutations are allelic and we have identified the mutant gene by genome sequencing...
October 24, 2016: Molecular Microbiology
Yuanwang Liu, Huiqing Chang, Zhaojun Li, Cheng Zhang, Yao Feng, Dengmiao Cheng
Social concern and awareness of the potential risk posed by environmental residues of antibiotics such as gentamicin in the development of antibiotic resistance genes have increased. The present study used laboratory-scale experiments to develop methods for gentamicin removal from the environment. A fungus, strain FZC3, which could remove gentamicin in submerged fermentation, was isolated from solid waste and sewage water from a gentamicin production factory. The fungus was identified as Aspergillus terreus by sequencing the PCR-amplified ITS fragments of its rRNA-coding genes and by its morphology...
October 24, 2016: Scientific Reports
Ma Ke, Xi Chen, Jia-Cheng Chen, Ying Wang, Xi-Meng Zhang, Fan Huang, Jun-Jiong Zheng, Xiong Chen, Wei Yu, Ke-Ling Cheng, Yan-Qing Feng, Huai-Yu Gu
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial for myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis (MS). Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice...
October 23, 2016: Journal of Neurochemistry
R L Openshaw, D M Thomson, J M Penninger, J A Pratt, B J Morris
RATIONALE: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. OBJECTIVE: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. METHODS: Attentional function in mice haploinsufficient for Map2k7 (Map2k7 (+/-) mice) was investigated using the five-choice serial reaction time task (5-CSRTT)...
October 24, 2016: Psychopharmacology
Bo Wang, Shannon J Walsh, Muhammad W Saif
5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents in solid tumors, including colon, gastric and breast cancers. The pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency leading to severe toxicity after administration of 5-flourouracil (5-FU) and capecitabine has been well-recognized. However, the data about the association of the target enzyme, thymidylate synthase (TYMS) with the toxicity of these agents is limited. A 50-year-old Caucasian woman with T2N2M0 Stage IIIB squamous cell rectal cancer after local surgical excision initiated 5-FU therapy with mitomycin-C and radiation therapy in the adjuvant setting...
September 21, 2016: Curēus
Indrajit Banerjee, Brijesh Sathian, Rajesh Kumar Gupta, Annavarapu Amarendra, Bedanta Roy, Pugazhandhi Bakthavatchalam, Archana Saha, Indraneel Banerjee
BACKGROUND: In developing countries like Nepal medicines can be acquired from the chemist's without of a prescription which sometime may have many drawbacks due to intake of excessive drugs without a proper diagnosis. The primary objective of the study was to find out the pattern of self-medication practice among the preclinical medical students at Manipal College of Medical Sciences. MATERIALS AND METHODS: This was a cross sectional study carried out using structured questionnaire at Manipal College of Medical Sciences, Pokhara, Nepal between November 2012- July 2014...
June 2016: Nepal journal of epidemiology
John Slattery, Derrick F MacFabe, Richard E Frye
Recent studies have highlighted the fact that the enteric microbiome, the trillions of microbes that inhabit the human digestive tract, has a significant effect on health and disease. Methods for manipulating the enteric microbiome, particularly through probiotics and microbial ecosystem transplantation, have undergone some study in clinical trials. We review some of the evidence for microbiome alteration in relation to childhood disease and discuss the clinical trials that have examined the manipulation of the microbiome in an effort to prevent or treat childhood disease with a primary focus on probiotics, prebiotics, and/or synbiotics (ie, probiotics + prebiotics)...
2016: Clinical Medicine Insights. Pediatrics
Glenn S Tillotson
Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward...
2016: Infectious Diseases
Liliana F Iannucci, Jingfeng Sun, Brijesh K Singh, Jin Zhou, Vincent A Kaddai, Antonia Lanni, Paul M Yen, Rohit A Sinha
Short-chain fatty acids (SCFAs) are gut microbial fermentation products derived from dietary fiber sources. Although depletion of gut microflora has been linked to the development of liver disease, the direct effects of SCFAs on intracellular hepatic processes are not well understood. In this study, we demonstrated that the SCFAs, propionate and butyrate, regulated autophagic flux in hepatic cells in a cell-autonomous manner. Induction of autophagy by SCFAs required PPARγ stimulation of Uncoupling Protein 2 (UCP2) expression that was associated with reduced intracellular ATP levels and activation of PRKAA1/AMPK (protein kinase, AMP-activated, alpha 1 catalytic subunit)...
October 20, 2016: Biochemical and Biophysical Research Communications
Matthew P Schreiber, Andrew F Shorr
Ventilator-associated pneumonia (VAP) is a distinct clinical entity characterized by an onset after 48 hours of the application of mechanical ventilation (MV). Protocols exist to aid in the prevention of VAP, but this infection carries a devastating impact on patient morbidity and potentially mortality. Areas covered: In this review we present key concepts from existing guidelines to aid clinicians. Challenges remain in defining this disease and, most importantly appropriate empiric antimicrobial treatment is the main determinant of outcome...
October 24, 2016: Expert Review of Anti-infective Therapy
Monica A Schmidt, Ken Pendarvis
Oilseed crops are global commodities for their oil and protein seed content. We have engineered the oilseed Camelina sativa to exhibit increased protein content with a slight decrease in oil content. The introduction of a phytoene synthase gene with an RNAi cassette directed to suppress the storage protein 2S albumin resulted in seeds with an 11-24 % elevation in overall protein. The phytoene synthase cassette alone produced enhanced β-carotene content of an average 275 ± 6.10 μg/g dry seed and an overall altered seed composition of 11 % less protein and comparable nontransgenic amounts of both oil and carbohydrates...
October 22, 2016: Transgenic Research
A N Severyukhina, N V Petrova, A M Yashchenok, D N Bratashov, K Smuda, I A Mamonova, N A Yurasov, D M Puchinyan, R Georgieva, H Bäumler, A Lapanje, D A Gorin
Increasing antimicrobial resistance requires the development of novel materials and approaches for treatment of various infections. Utilization of photodynamic therapy represents an advanced alternative to antibiotics and metal-based agents. Here, we report the fabrication of electrospun material that possesses benefits of both topical antimicrobial and photodynamic therapies. This material combines chitosan, as a biocompatible polymer, and a second generation photosensitizer. The incorporation of photosensitizer doesn't affect the material morphology and its nearly uniform distribution in fibers structure was observed by confocal Raman microscopy...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Shilpi Agarwal, Inderjeet Tyagi, Vinod Kumar Gupta, Maryam Sohrabi, Sanaz Mohammadi, Ahmad Nozad Golikand, Ali Fakhri
Sol-gel and precipitation reaction methods were used to synthesize Un-doped and Fe-doped SnO2/Co3O4 nanocomposites under UV light; the synthesized nanocomposites were applied for the photocatalytic degradation of metronidazole antibiotic. The developed photo catalyst was well characterized using energy dispersive X-ray spectrometer (EDX), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), field emission scanning electron microscopy (FE-SEM), UV-Visible and photoluminescence (PL) spectroscopy. Effective parameters such as pH, photocatalyst dose and contact time was optimized and well investigated...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Aura Falco, Yusibeska Ramos, Esther Franco, Alegría Guzmán, Howard Takiff
BACKGROUND: Klebsiella pneumoniae is a bacterial pathogen that has developed resistance to multiple antibiotics and is a major cause of nosocomial infections worldwide. Carbapenemase-producing Klebsiella pneumoniae have been isolated in many hospitals in Venezuela, but they have not been well-studied. The aim of this study was to characterize carbapenem-resistant Klebsiella pneumoniae isolates from the pediatric service of a hospital located in Anzoategui State, in the eastern part of Venezuela...
October 22, 2016: BMC Infectious Diseases
Mor Shlezinger, Yael Houri-Haddad, Shunit Coppenhagen-Glazer, Grégory Resch, Yok-Ai Que, Shaul Beyth, Elisheva Dorfman, Ronen Hazan, Nurit Beyth
Dental diseases are perhaps the most prevalent infection-related diseases in humans. Biofilm is involved in almost every infectious disease compromising oral health, notably caries, periodontal disease, gingivitis, endodontic infections and peri-implantitis. Current therapies of biofilm-derived oral infections lack sensitivity; they are not species-specific and kill pathogenic species as well as commensal species, which are protective against the formation of pathogenic biofilms. Moreover, antibiotics have a limited effect on biofilm and are almost unused in oral diseases...
September 30, 2016: Current Topics in Medicinal Chemistry
T Koiava, D Gonçalves, J Palmeira, K Arobelidze, M Tediashvili, L Akhvlediani, H Ferreira
Research describing the epidemiology of antibiotic resistant microbes is vital to the proactive development of new antimicrobial agents. In the last years, CTX-M extended-spectrum β-lactamases (ESBLs) have emerged worldwide and have replaced classical TEM and SHV-type ESBLs in many countries. CTX-M-15 is currently the most frequent, with a pandemic distribution, and its rapid spread is facilitated by incorporation of resistance genes in mobile genetic elements. The ESBL is efficacious in Gram-negative bacteria and thus closely associated with nosocomial environments, often colonizing the intestines, particularly in older and dependent patients...
September 2016: Georgian Medical News
Tomoshi Sugiyama, Koji Kawaguchi, Noriyasu Usami, Kohei Yokoi
We herein describe a surgical case of pulmonary involvement in Takayasu's arteritis with pulmonary infections of nontuberculous mycobacteria. A 24-year-old female was admitted to our hospital because of a recurrent fever, and contrast-enhanced computed tomography of the chest revealed the occlusion of the right pulmonary artery and cavitary lesions in the right lower lobe of the lung. A further examination of the neck revealed the occlusion of aortic branches, and the patient was diagnosed with Takayasu's arteritis...
October 21, 2016: General Thoracic and Cardiovascular Surgery
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