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31.
Haroon Mohammad Ahmed AbdelKhalek Nader S. Abutaleb Mohamed N. Seleem 《International journal of antimicrobial agents》2018,51(6):897-904
Enterococci are commensal micro-organisms present in the gastrointestinal tract of humans. Although normally innocuous to the host, strains of enterococcus exhibiting resistance to vancomycin (VRE) have been associated with high rates of infection and mortality in immunocompromised patients. Decolonization of VRE represents a key strategy to curb infection in highly-susceptible patients. However, there is a dearth of decolonizing agents available clinically that are effective against VRE. The present study found that niclosamide, an anthelmintic drug, has potent antibacterial activity against clinical isolates of vancomycin-resistant Enterococcus faecium (minimum inhibitory concentration 1–8?µg/mL). E. faecium mutants exhibiting resistance to niclosamide could not be isolated even after multiple (10) serial passages. Based upon these promising in-vitro results and the limited permeability of niclosamide across the gastrointestinal tract (when administered orally), niclosamide was evaluated in a VRE colonization-reduction murine model. Remarkably, niclosamide outperformed linezolid, an antibiotic used clinically to treat VRE infections. Niclosamide was as effective as ramoplanin in reducing the burden of vancomycin-resistant E. faecium in the faeces, caecal content and ileal content of infected mice after only 8 days of treatment. Linezolid, in contrast, was unable to decrease the burden of VRE in the gastrointestinal tract of mice. The results obtained indicate that niclosamide warrants further evaluation as a novel decolonizing agent to suppress VRE infections. 相似文献
32.
Phytochemical investigations on the chloroform soluble fraction of the whole plant of Withania somnifera led to the isolation of 20β hydroxy-1-oxo(22R)-witha-2,5,24 trienolide 1, (20R, 22R-14α, 20α)-dihydroxy-1-oxowitha-2,5,16,24 tetraenolide 2, and (20R, 22R)-1-oxo-5α, 8β-dihydroxywitha-6α, 7β-epoxide-2,24-dienolide (withasomilide) 3. The structures of these compounds were confirmed through spectral studies in comparison with data in the literature. These isolated compounds (1–3) exhibited potent inhibition against α-glucosidase with IC50 values of 98.60, 38.20, and 40.65 μg/ml respectively. 相似文献
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Joshua Winer MD Mazen Zenati MD PhD Lekshmi Ramalingam MD Heather Jones MPA-C Amer Zureikat MD Matthew Holtzman MD Kenneth Lee MD Steven Ahrendt MD James Pingpank MD Herbert J. Zeh MD David L. Bartlett MD Haroon A. Choudry MD 《Annals of surgical oncology》2014,21(5):1456-1462
Background
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) of colorectal origin increases survival (OS) compared to systemic chemotherapy alone. Signet ring histology demonstrates aggressive behavior with poor survival. We sought to determine whether CRS/HIPEC increases survival in this subset of patients.Methods
We reviewed 67 patients with PC of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology from a prospective database between May 2001 and August 2011. Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival.Results
Complete CRS (CC-0/1) was achieved in 77 % (CRC) and 73 % (AP) of patients. Progression-free survival (PFS) and OS were 9 and 12 months in CRC and 12 and 21 months in AP patients. In the CRC group, univariate predictors of poor survival included female gender, age, American Society of Anesthesiologists score, preoperative albumin, completeness of cytoreduction, and morbidity. In a multivariate Cox regression model, incomplete cytoreduction (CC-2/3) and female gender were joint significant predictors of poor survival. In the AP group, significant univariate predictors of poor survival included higher EBL and PCI score. In a multivariate Cox regression model, blood loss of >500 ml and a body mass index of <25 kg/m2 were joint significant predictors of poor survival.Conclusions
AP signet cell tumors demonstrate a more favorable outcome than CRC signet cell tumors after CRC/HIPEC for carcinomatosis, suggesting an underlying difference in biology. CRS/HIPEC does not confer survival benefit in colorectal signet ring carcinomatosis unless complete cytoreduction can be achieved, whereas appendiceal signet ring carcinomatosis may benefit, regardless of resectability. 相似文献36.
Christopher Sainsbury MD Jingya Wang PhD Krishna Gokhale MSc Dionisio Acosta-Mena PhD Samir Dhalla MRPharmS Nathan Byne Joht Singh Chandan PhD Astha Anand BMBCh Jennifer Cooper MBBCh Kelvin Okoth MPH Anuradhaa Subramanian MSc Mansoor N. Bangash PhD Thomas Taverner PhD Wasim Hanif PhD Sandip Ghosh FRCP Parth Narendran PhD Kar K. Cheng PhD Tom Marshall PhD Georgios Gkoutos PhD Konstantinos Toulis PhD Neil Thomas PhD Abd Tahrani PhD Nicola J. Adderley PhD Shamil Haroon PhD Krishnarajah Nirantharakumar MD 《Diabetes, obesity & metabolism》2021,23(1):263-269
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Ultrastructural localization of human platelet thrombospondin, fibrinogen, fibronectin, and von Willebrand factor in frozen thin section 总被引:7,自引:0,他引:7
We have investigated the localization of thrombospondin (TSP), fibrinogen, fibronectin, and von Willebrand factor in human platelets by transmission electron microscopy of antibody-stained ultrathin frozen sections. In negatively stained thin sections, alpha granules were identified on the basis of their smooth, roughly spherical shape, size, single limiting electron-lucent 100 A membrane, and frequent presence of electron-dense nucleoid. In contrast, mitochondria exhibited characteristic double membranes and cristae. Sections were separately stained with affinity-purified polyclonal antibodies to these proteins as well as with three monoclonal anti-TSP antibodies. Antibody specificity was documented in radioimmunoassays, by immunofluorescent cross-blocking, and by staining of bands of appropriate mobility in Western blots of whole platelets. Bound antibody was visualized using a 5-nm colloidal gold-avidin conjugate. In resting cells, staining of virtually all alpha granules was observed for all four proteins. In contrast, consistent staining was absent from other organelles, including plasma membranes, mitochondria, and vacuolar structures that may represent the open canalicular system. 相似文献