40 research outputs found
Nonspecific Prophylaxis of Hemorrhagic Fever with Renal Syndrome in the Republic of Bashkortostan
Scientifically based typing of HFRS foci, ecological-epizootiological monitoring and a number of sanitary-and-hygiene, sanitary-and-technical, agrotechnical, forestry as well as deratization and disinfection measures were carried out. In addition, information-explanatory work among the population was done. That enabled to eliminate group diseases in Ufa, lower to single cases the risk of HFRS infection of the population in woodland territory and reduce average annual morbidity in the city from high to middle level
Effect of calcium pantothenate on the diurnal rhythm and rate of epithelial cell proliferation in the gastric mucosa of rats
Enhancing the Oral Absorption of Kinase Inhibitors Using Lipophilic Salts and Lipid-Based Formulations
The
absolute bioavailability of many small molecule kinase inhibitors
(smKIs) is low. The reasons for low bioavailability are multifaceted
and include constraints due to first pass metabolism and poor absorption.
For smKIs where absorption limits oral bioavailability, low aqueous
solubility and high lipophilicity, often in combination with high-dose
requirements have been implicated in low and variable absorption,
food-effects, and absorption-related drug–drug interactions.
The current study has evaluated whether preparation of smKIs as lipophilic
salts/ionic liquids in combination with coadministration with lipid-based
formulations is able to enhance absorption for examples of this compound
class. Lipophilic (docusate) salt forms of erlotinib, gefitinib, ceritinib,
and cabozantinib (as example smKIs demonstrating low aqueous solubility
and high lipophilicity) were prepared and isolated as workable powder
solids. In each case, the lipophilic salt exhibited high and significantly
enhanced solubility in lipidic excipients (>100 mg/g) when compared
to the free base or commercial salt form. Isolation as the lipophilic
salt facilitated smKI loading in model lipid-based formulations at
high concentration, increased in vitro solubilization
at gastric and intestinal pH and in some cases increased oral absorption
(∼2-fold for cabozantinib formulations in rats). Application
of a lipophilic salt approach can therefore facilitate the use of
lipid-based formulations for examples of the smKI compound class where
low solubility limits absorption and is a risk factor for increased
variability due to food-effects
Enhancing the Oral Absorption of Kinase Inhibitors Using Lipophilic Salts and Lipid-Based Formulations
Assignment of 1H, 13C and 15N backbone resonances of Escherichia coli LpxC bound to L-161,240
Structure, function and selective inhibition of bacterial acetyl-coa carboxylase
Acetyl-CoA carboxylase (ACC) catalyses the first committed step in fatty acid biosynthesis: a metabolic pathway required for several important biological processes including the synthesis and maintenance of cellular membranes. ACC employs a covalently attached biotin moiety to bind a carboxyl anion and then transfer it to acetyl-CoA, yielding malonyl-CoA. These activities occur at two different subsites: the biotin carboxylase (BC) and carboxyltransferase (CT). Structural biology, together with small molecule inhibitor studies, has provided new insights into the molecular mechanisms that govern ACC catalysis, specifically the BC and CT subunits. Here, we review these recent findings and highlight key differences between the bacterial and eukaryotic isozymes with a view to establish those features that provide an opportunity for selective inhibition. Especially important are examples of highly selective small molecule inhibitors capable of differentiating between ACCs from different phyla. The implications for early stage antibiotic discovery projects, stemming from these studies, are discussed.S. W. Polyak, A. D. Abell, M. C. J. Wilce, L. Zhang, G. W. Booke