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171.
172.
Suresh B. Lakshminarayana Helena I. M. Boshoff Joseph Cherian Sindhu Ravindran Anne Goh Jan Jiricek Mahesh Nanjundappa Amit Nayyar Meera Gurumurthy Ramandeep Singh Thomas Dick Francesca Blasco Clifton E. Barry III Paul C. Ho Ujjini H. Manjunatha 《PloS one》2014,9(8)
PA-824 is a bicyclic 4-nitroimidazole, currently in phase II clinical trials for the treatment of tuberculosis. Dose fractionation pharmacokinetic-pharmacodynamic studies in mice indicated that the driver of PA-824 in
vivo efficacy is the time during which the free drug concentrations in plasma are above the MIC (fT>MIC). In this study, a panel of closely related potent bicyclic 4-nitroimidazoles was profiled in both in
vivo PK and efficacy studies. In an established murine TB model, the efficacy of diverse nitroimidazole analogs ranged between 0.5 and 2.3 log CFU reduction compared to untreated controls. Further, a retrospective analysis was performed for a set of seven nitroimidazole analogs to identify the PK parameters that correlate with in
vivo efficacy. Our findings show that the in
vivo efficacy of bicyclic 4-nitroimidazoles correlated better with lung PK than with plasma PK. Further, nitroimidazole analogs with moderate-to-high volume of distribution and Lung to plasma ratios of >2 showed good efficacy. Among all the PK-PD indices, total lung T>MIC correlated the best with in
vivo efficacy (rs = 0.88) followed by lung Cmax/MIC and AUC/MIC. Thus, lung drug distribution studies could potentially be exploited to guide the selection of compounds for efficacy studies, thereby accelerating the drug discovery efforts in finding new nitroimidazole analogs. 相似文献
173.
Salt tolerance was studied in the callus cultures of Suaeda nudiflora Moq. a dicotyledonous succulent halophyte. Growth was significantly inhibited at 50, 100, 150 and 200 mM NaCl. Inorganic
ions and proline accumulated in response to salinity. Ion accumulation pattern reflected the utilization of Na+ as an osmoticum. Na+/K+ ratio rose steadily as a function of external NaCl concentration. Salt stress enhanced the activity of peroxidase, whereas
it decreased activities of superoxide dismutase and catalase.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
174.
A nonhistone protein component (NHPIns) firmly bound to DNA of rat kidney nuclei has been isolated and partially characterized. In vivo studies show that this protein specifically incorporates 35 to 45 times more 203Hg than any other nuclear protein fractions. No difference in the ratio of NHPIns to DNA between normal and mercury-poisoned rat kidney nuclei was observed. NHPIns protein gives a single major band by sodium dodecyl sulfate gel electrophoresis. Electrophoretic pattern as well as amino acid composition of this protein isolated from both normal and mercurypoisoned rats are also found to be similar. Cysteine content is 1.3 to 1.4 mole per cent. 相似文献
175.
Philip T. Cherian Leonid N. Koikov Matthew D. Wortman James J. Knittel 《Bioorganic & medicinal chemistry letters》2009,19(8):2215-2219
A homology model of the p110α catalytic subunit of PI3Kα was generated from the p110γ crystal structure. Using this model, an isonicotinic scaffold was designed for chemically exploring the PI3Kα and γ binding sites. A focused library of derivatives was synthesized and tested. The morpholine acids 5a and 5b proved to be the most potent analogs. 相似文献
176.
177.
Optical tweezers (infrared laser-based optical traps) have emerged as a powerful tool in molecular and cell biology. However, their usefulness has been limited, particularly in vivo, by the potential for damage to specimens resulting from the trapping laser. Relatively little is known about the origin of this phenomenon. Here we employed a wavelength-tunable optical trap in which the microscope objective transmission was fully characterized throughout the near infrared, in conjunction with a sensitive, rotating bacterial cell assay. Single cells of Escherichia coli were tethered to a glass coverslip by means of a single flagellum: such cells rotate at rates proportional to their transmembrane proton potential (. J. Mol. Biol. 138:541-561). Monitoring the rotation rates of cells subjected to laser illumination permits a rapid and quantitative measure of their metabolic state. Employing this assay, we characterized photodamage throughout the near-infrared region favored for optical trapping (790-1064 nm). The action spectrum for photodamage exhibits minima at 830 and 970 nm, and maxima at 870 and 930 nm. Damage was reduced to background levels under anaerobic conditions, implicating oxygen in the photodamage pathway. The intensity dependence for photodamage was linear, supporting a single-photon process. These findings may help guide the selection of lasers and experimental protocols best suited for optical trapping work. 相似文献
178.
Because ethanol elicits a dose-dependent hydrolysis of brain sialogangliosides, we tested the possibility that injected gangliosides might antagonize intoxicating doses of ethanol. Clear anti-intoxication effects were seen at 24 hr post-injection of mixed mouse-brain gangliosides at 125-130 mg/kg, but not at lower or higher doses. Sleep time was reduced on the order of 50%, and roto-rod agility was significantly enhanced. Sialic acid (SA) similarly antagonized ethanol; however, the precursor of SA, N-acetyl-D-mannosamine, as well as ceramide and asialoganglioside did not. 相似文献
179.
Cellular antigens of Trypanosoma lewisi have been located with ferritin-conjugated antibody (FCA) at the ultrastructural level. Incubation of live T. lewisi with antibodies from infected rats and ferritin-labeled rabbit anti-rat γ-globulin induced aggregation of surface antigens in the flagellar pockets, the desmosomal regions, and the flagellar membranes of parasites. Aggregation of surface antigens was not observed when the trypanosomes were incubated with γ-globulin and FCA at low temperatures (0–4 C). Sections of trypanosomes incubated at 37 C for 15 or 30 min after incubation at 0 C with FCA showed internalization of FCA in membrane-bound vesicles. Studying the movement and aggregation of these parasites' surface antigens may give information about the molecular dynamics of the plasma membrane and provide insights into the trypanosomes' antigenic modulation and the hosts' immunological responses. 相似文献
180.
Afiya Jahan Tanjia Taher Nipa SM Majharul Islam Md. Helal Uddin Md. Sadiqul Islam Md. Shahjahan 《Zeitschrift fur angewandte Ichthyologie》2019,35(4):994-1003
Salinity intrusion in the coastal freshwater rivers due to climate change and construction of the dam in the upstream rivers are alarming in aquaculture. Hence, an experiment was conducted to know the effects of salinity on growth performance, hemato‐biochemical parameters and erythrocytes structure in a commercially cultivable catfish species, striped catfish (Pangasianodon hypophthalmus). Firstly, median lethal concentration (LC50) of salinity for striped catfish was determined and then the fish were exposed to three salinity conditions (4, 8 and 12‰) and a control (0‰). Fish were sacrificed at day 7, 14, 28 and 56 after the start of salinity exposure. The 96 hr LC50 value was found to be 14.87‰. Salinity levels from freshwater to 8‰ showed optimal conditions with high survival rate and good growth performances of fish in terms of weight gain and specific growth rate (SGR). Interestingly, the lowest food conversion ratio (FCR) was found in 4‰ group. The hemoglobin (Hb) level and number of red blood cells (RBCs) were found to be decreased significantly in 8 and 12‰ compared to 0 and 4‰ at the initial days of exposure, while number of white blood cells (WBCs) and glucose level showed opposite scenario. Frequencies of ENA (erythrocytic nuclear abnormalities) and ECA (erythrocytic cellular abnormalities) were significantly increased with increasing salinities in the initial days of exposure. Overall, findings of the present study revealed that striped catfish might be suitable fish species for culture in the brackish water containing salinity up to 10‰. 相似文献