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https://www.readbyqxmd.com/read/28822333/virtual-screening-and-repositioning-of-inconclusive-molecules-of-beta-lactamase-bioassays-a-data-mining-approach
#1
Akshata Gad, Andrew Titus Manuel, Jinuraj K R, Lijo John, Sajeev R, Shanmuga Priya V G, Abdul Jaleel U C
This study focuses on the best possible way forward in utilizing inconclusive molecules of PubChem bioassays AID 1332, AID 434987 and AID 434955, which are related to beta-lactamase inhibitors of Mycobacterium tuberculosis (Mtb). The inadequacy in the experimental methods that were observed during the invitro screening resulted in an inconclusive dataset. This could be due to certain moieties present within the molecules. In order to reconsider such molecules, insilico methods can be suggested in place of invitro methods For instance, datamining and medicinal chemistry methods: have been adopted to prioritise the inconclusive dataset into active or inactive molecules...
July 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28821804/nos2-deficient-mice-with-hypoxic-necrotizing-lung-lesions-predict-outcomes-of-tuberculosis-chemotherapy-in-humans
#2
Martin Gengenbacher, Maria A Duque-Correa, Peggy Kaiser, Stefanie Schuerer, Doris Lazar, Ulrike Zedler, Stephen T Reece, Amit Nayyar, Stewart T Cole, Vadim Makarov, Clifton E Barry Iii, Véronique Dartois, Stefan H E Kaufmann
During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2 (-/-) mice incapable of NO-production in immune cells as microbial defence uniformly develop hypoxic necrotizing lung lesions, widely observed in human TB. To study the impact of hypoxic necrosis on the efficacy of antimycobacterials and drug candidates, we subjected Nos2 (-/-) mice with TB to monotherapy before or after establishment of human-like pathology...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821299/pknb-remains-an-essential-and-a-conserved-target-for-drug-development-in-susceptible-and-mdr-strains-of-m-tuberculosis
#3
Anamika Gupta, Sudhir K Pal, Divya Pandey, Najneen A Fakir, Sunita Rathod, Dhiraj Sinha, S SivaKumar, Pallavi Sinha, Mycal Periera, Shilpa Balgam, Gomathi Sekar, K R UmaDevi, Shampa Anupurba, Vijay Nema
BACKGROUND: The Mycobacterium tuberculosis (M.tb) protein kinase B (PknB) which is now proved to be essential for the growth and survival of M.tb, is a transmembrane protein with a potential to be a good drug target. However it is not known if this target remains conserved in otherwise resistant isolates from clinical origin. The present study describes the conservation analysis of sequences covering the inhibitor binding domain of PknB to assess if it remains conserved in susceptible and resistant clinical strains of mycobacteria picked from three different geographical areas of India...
August 18, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28820984/identification-of-m-tuberculosis-antigens-in-the-sera-of-tuberculosis-patients-using-biomimetic-affinity-chromatography-in-conjunction-with-esi-cid-ms-ms
#4
Guorong Ma, Jinting Pan, Jincheng Han, Lina Gao, Shulin Zhang, Rongxiu Li
The profiling of abnormally-expressed proteins in host cells using mass spectrometry (MS) analysis is a classical approach for screening disease-associated biomarkers in clinical diagnosis. However, few pathogen-specific antigens can currently be detected in serum using this proteomic approach, since these are very low-abundant proteins that are easily masked by host high-abundant proteins. Identification of pathogen-specific antigens in the sera of tuberculosis patients is crucial for the clinical diagnosis of this infectious disease, especially in immune-compromised patients...
July 31, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28820946/proteogenomic-investigation-of-strain-variation-in-clinical-mycobacterium-tuberculosis-isolates
#5
Tiaan Heunis, Anzaan Dippenaar, Robin M Warren, Paul D van Helden, Ruben G van der Merwe, Nicolaas C Gey van Pittius, Arnab Pain, Samantha L Sampson, David L Tabb
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28820170/paradoxical-worsening-of-a-case-of-tb-subretinal-abscess-with-serpiginous-like-choroiditis-following-the-initiation-of-antitubercular-therapy
#6
Sudha K Ganesh, B Sowkath Ali
A 37-year-old immunocompetent male patient presented with the blurring of vision, both eyes for the past1 year. Fundus examination revealed bilateral multiple subretinal abscesses with areas of healed serpiginous-like choroiditis. Laboratory investigations showed positive tuberculin skin test, positive QuantiFERON TB-Gold Test, and high resolution computed tomography chest showed enlarged mediastinal lymph nodes. The aqueous sample revealed polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis (MTB) (MPB64 genome)...
August 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28819600/extensively-drug-resistant-tuberculosis-of-the-lumbar-spine-in-a-six-year-old-child-a-case-report
#7
Siddharth Sanjay Shah, Aakanksha Arvind Goregaonkar, Arvind Balkrishna Goregaonkar
INTRODUCTION: The emergence of extensively drug-resistant tuberculosis (XDR-TB) is a challenging paradigm shift faced by the TB control programs worldwide today. The treatment is further compounded with unique management difficulties faced in pediatric patients. Treatment of XDR-TB requires prolonged chemotherapy with second-line drugs which offer lesser potency and increased risk of drug-related side effects. We present a case of spinal XDR-TB in a child, managed with extended second-line antitubercular chemotherapy (ATT)...
March 2017: Journal of Orthopaedic Case Reports
https://www.readbyqxmd.com/read/28819499/multiple-jejunal-perforation-secondary-to-intestinal-tuberculosis-infection-a-case-report
#8
Anthony Lyonga Ngonge, Domin Sone Majunda Ekaney, Carlson-Babila Sama, Joffi Musonge-Effoe, Valery Sammah Effoe, Gerald Ekwen
Abdominal tuberculosis (TB) may affect any part of the gastrointestinal tract resulting in significant morbidity and mortality. There is an increase in the incidence of abdominal TB favored by the emergence of multi-drug resistant Mycobacterium tuberculosis and immunosuppression especially from HIV co-infection. Our case is that of a 31 year old HIV-positive woman, adherent to antiretroviral therapy, who presented with a 2 month history of progressive abdominal distention, drenching night sweat and fatigue, but without fever...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28819202/mechanism-of-transformation-in-mycobacteria-using-a-novel-shockwave-assisted-technique-driven-by-in-situ-generated-oxyhydrogen
#9
Akshay Datey, Janardhanraj Subburaj, Jagadeesh Gopalan, Dipshikha Chakravortty
We present a novel method for shockwave-assisted bacterial transformation using a miniature oxyhydrogen detonation-driven shock tube. We have obtained transformation efficiencies of about 1.28 × 10(6), 1.7 × 10(6), 5 × 10(6), 1 × 10(5), 1 × 10(5) and 2 × 10(5) transformants/µg of DNA for Escherichia coli, Salmonella Typhimurum, Pseudomonas aeruginosa, Mycobacterium smegmatis, Mycobacterium tuberculosis (Mtb) and Helicobacter pylori respectively using this method which are significantly higher than those obtained using conventional methods...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819046/tuberculous-tales-an-east-london-experience
#10
REVIEW
Apeksha M Shah, Dominika Raciborska, Matthew Stevens, Sharmilee Gnanapavan, Veronica L C White, Benjamin Turner
Tuberculous meningitis presents a diagnostic and therapeutic challenge, and considering its long history and increasing global incidence, the evidence base for its treatment is relatively scanty. Many UK neurologists will have little first-hand experience of this deadly condition, and if faced with a patient with possible tuberculous meningitis will find decision making less than straightforward. In parts of East London (UK) the rates of tuberculosis and tuberculous meningitis are among the highest in Western Europe, and so the neurologists and respiratory physicians at the Royal London Hospital have encountered many such patients over the years...
August 17, 2017: Practical Neurology
https://www.readbyqxmd.com/read/28818169/tuberculosis-of-open-cholecystectomy-wound
#11
Nauman Ahmed, Hammad Naeem Hammad Naeem Rana
Tuberculosis of the wound is a rare entity. A50-year lady presented with an "on and off discharging wound" from the postoperative wound site of open cholecystectomy, which was done 7 years ago. Patient did not respond to standard antibiotic treatment regimens; and also the culture remained equivocal during this period. We explored the wound and found a mass in subcutaneous tissue. Resection of mass was done and wound left open for closure by secondary intention. Histopathology of the resected mass revealed tuberculosis...
July 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28817714/insights-into-secular-trends-of-respiratory-tuberculosis-the-20th-century-maltese-experience
#12
Lianne Tripp, Larry A Sawchuk
Over half a century ago, McKeown and colleagues proposed that economics was a major contributor to the decline of infectious diseases, including respiratory tuberculosis, during the 19th and 20th centuries. Since then, there is no consensus among researchers as to the factors responsible for the mortality decline. Using the case study of the islands of Malta and Gozo, we examine the relationship of economics, in particular, the cost of living (Fisher index) and its relationship to the secular trends of tuberculosis mortality...
2017: PloS One
https://www.readbyqxmd.com/read/28814938/superior-mesenteric-artery-syndrome-in-association-with-abdominal-tuberculosis-an-eye-opener
#13
Shuchi Bhatt, Biswajit Mishra, Anupama Tandon, Smita Manchanda, G Parthsarathy
Superior Mesenteric Artery Syndrome (SMAS) is a rare clinical entity presenting as acute or chronic upper gastrointestinal obstruction. It occurs due to compression of third part of duodenum between abdominal aorta and overlying superior mesenteric artery caused by a decrease in angle between the two vessels. Rapid loss of retroperitoneal fat, in conditions leading to severe weight loss is the main factor responsible for this disorder. Superior mesenteric artery syndrome in association with abdominal tuberculosis has not been reported earlier to the best of our knowledge...
May 2017: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28814447/acute-myocarditis-secondary-to-cardiac-tuberculosis
#14
Alice Cowley, Laura Dobson, John Kurian, Christopher Saunderson
Isolated myocardial involvement in tuberculosis is exceedingly rare but there are reports it can present with sudden cardiac death, atrioventricular block, ventricular arrhythmias or congestive cardiac failure. We report the case of a 33 year-old male, of South Asian descent, who presented with chest pain, shortness of breath and an abnormal ECG. The patient had no significant past medical history and coronary angiogram showed no evidence of coronary artery disease. Of note the patient had recently been discharged from a local district hospital with an episode of myocarditis...
August 16, 2017: Echo Research and Practice
https://www.readbyqxmd.com/read/28812125/recombinant-expression-and-biochemical-characterization-of-mycobacterium-tuberculosis-3fe-4s-ferredoxin-rv1786
#15
Yun Lu, Feng Qiao, Yue Li, Xiao-Hong Sang, Cong-Ran Li, Jian-Dong Jiang, Xin-Yi Yang, Xue-Fu You
Ferredoxins are iron-sulfur protein that mediate electron transfer in cytochrome P450 mono-oxygenase (CYP)-related catalytic reactions in a wide variety of organisms. Rv1786 is a putative ferredoxin, encoded by a gene located downstream of the gene encoding CYP143A1 in the Mycobacterium tuberculosis genome. However, the structure and function of Rv1786 have remained unclear. Here, the recombinant Mtb Rv1786 was expressed, purified as a His-tagged form and characterized with [3Fe-4S] clusters as its cofactors using a series of measurements including SDS-PAGE, western blot, UV/Visible, MALDI-TOF/TOF-MS, and electron paramagnetic resonance spectroscopic analysis...
August 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28811354/safety-and-efficacy-of-baricitinib-through-128-weeks-in-an-open-label-longterm-extension-study-in-patients-with-rheumatoid-arthritis
#16
Edward C Keystone, Mark C Genovese, Douglas E Schlichting, Inmaculada de la Torre, Scott D Beattie, Terence P Rooney, Peter C Taylor
OBJECTIVE: To assess the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) up to 128 weeks in a phase IIb study (NCT01185353). METHODS: After a 24-week blinded period, eligible patients entered an initial 52-week open-label extension (OLE); patients receiving 8 mg once daily (QD) continued with that dose and all others received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at investigator discretion when ≥ 6 tender and ≥ 6 swollen joints were present...
August 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28811344/the-capacity-of-mycobacterium-tuberculosis-to-survive-iron-starvation-might-enable-it-to-persist-in-iron-deprived-microenvironments-of-human-granulomas
#17
Krishna Kurthkoti, Hamel Amin, Mohlopheni J Marakalala, Saleena Ghanny, Selvakumar Subbian, Alexandra Sakatos, Jonathan Livny, Sarah M Fortune, Michael Berney, G Marcela Rodriguez
This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28810840/the-association-between-tuberculosis-and-the-development-of-insulin-resistance-in-adults-with-pulmonary-tuberculosis-in-the-western-sub-district-of-the-cape-metropole-region-south-africa-a-combined-cross-sectional-cohort-study
#18
Lauren Philips, Janicke Visser, Daan Nel, Renée Blaauw
BACKGROUND: The existence of a bi-directional relationship between tuberculosis (TB) and insulin resistance (IR)/diabetes has been alluded to in literature. Although diabetes has been linked to increased tuberculosis risk, the relationship between tuberculosis as a causative factor for IR remains unclear. The study aimed to determine if an association existed between tuberculosis and IR development in adults with newly diagnosed pulmonary tuberculosis at baseline. It was additionally aimed to document changes in IR status during TB follow-up periods...
August 15, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28809619/the-effect-of-hiv-status-on-clinical-outcomes-of-surgical-sepsis-in-kwazulu-natal-province-south-africa
#19
Samantha Green, Victor Y Kong, Jocinta Odendaal, Benn Sartorius, Damian L Clarke, Petra Brysiewicz, Jereme L Bruce, Grant L Laing, Wanda Bekker
BACKGROUND: KwaZulu-Natal Province, South Africa (SA), has long been the epicentre of the HIV epidemic, but the impact of HIV co-infection on the clinical outcomes of emergency surgical patients with sepsis remains largely unknown. OBJECTIVE: To review our experience with the management of patients with HIV co-infection and to compare the disease spectrum and outcome with those without HIV infection. METHODS: A retrospective study was undertaken at the Pietermaritzburg Metropolitan Surgical Service (PMSS), SA over a 5-year period from January 2010 to December 2014...
July 28, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28808611/red-snappers-and-red-herrings-pelvic-tuberculosis-causing-elevated-ca-125-and-mimicking-advanced-ovarian-cancer-a-case-report-and-literature-review
#20
Johnnie Alphonse Yates, Olivia Ann Collis, Thanasak Sueblinvong, Tarquin Kamakana Collis
Female genital tuberculosis (FGTB) is a form of extra-pulmonary tuberculosis that has been primarily described in developing countries, where it is an important cause of infertility, ectopic pregnancy, and miscarriage. FGTB is rare in the United States and because its clinical presentation is non-specific and often insidious, FGTB may be misdiagnosed as a gynecologic malignancy or endometriosis. The tendency of tuberculosis to dramatically increase serum CA 125 levels contributes to the potential for FGTB to be mistaken for ovarian cancer in particular...
August 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
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