Hyaluronic Acid: Its Role in Voice

The extracellular matrix (ECM), once regarded simply as a structural scaffold, is now recognized as an important modulator of cellular behavior and function. One component that plays a prominent role in this process is hyaluronic acid (HA)--a molecule found in many different tissues. Research into the roles of HA indicates that it plays a key role in tissue viscosity, shock absorption, and space filling. Specifically, research into the role of HA in laryngology indicates that it has profound effects on the structure and viscosity of vocal folds. This article provides an introduction to the structure and biological functions of HA and its importance in voice. In addition, an overview of the pharmaceutical applications of HA is discussed.     

Vocal Nodules and Laryngeal Morphology

Our purpose was to study the occurrence of vocal fold nodules under conditions of habitual vocal abuse associated with increased laryngeal muscle tension, to identify the existence of a relationship between vocal nodules and laryngeal morphology. We studied one group of 30 subjects with vocal nodules, 18 to 50 years old, who were compared with two control groups, one of females and one of males, consisting of 30 subjects each. The parameters evaluated were: type of vocal folds coaptation, glottic proportion (GP) and abduction angle (AA), obtained by videotelelaryngoscopy. In the nodules group, the larynges presented a mean value of GP similar to that of the female group, both of which were lower than the mean GP value of the male group. On the other hand, the mean AA was lower than the one in the female group, and closer to the one in the male group. We concluded that vocal nodules were present only in larynges with a predominantly young female morphology, with functional limitations of abduction.     

Bisubstrate adenylation inhibitors of biotin protein ligase from Mycobacterium tuberculosis

The mycobacterial biotin protein ligase (MtBPL) globally regulates lipid metabolism in Mtb through the posttranslational biotinylation of acyl coenzyme A carboxylases involved in lipid biosynthesis that catalyze the first step in fatty acid biosynthesis and pyruvate coenzyme A carboxylase, a gluconeogenic enzyme vital for lipid catabolism. Here we describe the design, development, and evaluation of a rationally designed bisubstrate inhibitor of MtBPL. This inhibitor displays potent subnanomolar enzyme inhibition and antitubercular activity against multidrug resistant and extensively drug resistant Mtb strains. We show that the inhibitor decreases in?vivo protein biotinylation of key enzymes involved in fatty?acid biosynthesis and that the antibacterial activity is MtBPL dependent. Additionally, the gene encoding BPL was found to be essential in M.?smegmatis. Finally, the X-ray cocrystal structure of inhibitor bound MtBPL was solved providing detailed insight for further structure-activity analysis. Collectively, these data suggest that MtBPL is a promising target for further antitubercular therapeutic development.     

A simple and selective kinetic spectrophotometric method for the determination of kanamycin using acetylacetone-formaldehyde reagent in N,N′-dimethylformamide medium

A simple, sensitive, and selective kinetic spectrophotometric method for the determination of kanamycin in pure form and pharmaceutical formulations is described. The method is based on the measurement of the intensity of the yellow chromogen formed by the reaction between kanamycin and acetylacetone-formaldehyde reagent in a N,N′-dimethyl formamide medium. The variable-time method was used to evaluate the rate of reaction of the colored chromogen formed at 410 nm. The reaction conditions were optimized and the calibration graph was found to be linear in the range 60–160 μg/mL. The results obtained by the developed and reference methods are in good agreement. Various statistical parameters were evaluated to establish the precision, accuracy, repeatability, and reproducibility of the proposed method. The text was submitted by the authors in English.     

Natural product inhibitors of fatty acid biosynthesis: synthesis of the marine microbial metabolites pseudopyronines A and B and evaluation of their anti-infective activities

Total syntheses of the title natural products, pseudopyronines A (1) and B (2), have been achieved using methyl β-oxo carboxylic ester starting materials. The natural products and a small set of structurally related compounds were evaluated for growth inhibitory activity against a range of pathogenic microorganisms and were found to exhibit good potency (IC₅₀≥0.46 μg/mL) and selectivity towards Leishmania donovani. Several of the compounds inhibited recombinant fatty acid biosynthesis enzymes from both Plasmodium falciparum and Mycobacterium tuberculosis, validating these targets in the search for new anti-infective agents.     

Surface ligands in the imprinting and binding of molecularly imprinted cross-linked micelles

Molecular recognition in water is challenging but water-soluble molecularly imprinted nanoparticle (MINP) receptors were produced readily by double cross-linking of surfactant micelles in the presence of suitable template molecules. When the micellar surface was decorated with different polyhydroxylated ligands, significant interactions could be introduced between the surface ligands and the template. Flexible surface ligands worked better than rigid ones to interact with the polar moiety of the template, especially for those template molecules whose water-exposed surface is not properly solvated by water. The importance of these hydrophilic interactions was examined in the context of different substrates, density of the surface ligands, and surface-cross-linking density of the MINP. Together with the hydrophobic interactions in the core, the surface hydrophilic interactions can be used to enhance the binding of guest molecules in water.     

Pathway-Selective Sensitization of Mycobacterium tuberculosis for Target-Based Whole-Cell Screening

Whole-cell screening of Mycobacterium tuberculosis (Mtb) remains a mainstay of drug discovery, but subsequent target elucidation often proves difficult. Conditional mutants that underexpress essential genes have been used to identify compounds with known mechanism of action by target-based whole-cell screening (TB-WCS). Here, the feasibility of TB-WCS in Mtb was assessed by generating mutants that conditionally express pantothenate synthetase (panC), diaminopimelate decarboxylase (lysA), and isocitrate lyase (icl1). The essentiality of panC and lysA, and conditional essentiality of icl1 for growth on fatty acids, was confirmed. Depletion of PanC and Icl1 rendered mutants hypersensitive to target-specific inhibitors. Stable reporter strains were generated for use in high-throughput screening, and their utility was demonstrated by identifying compounds that display greater potency against a PanC-depleted strain. These findings illustrate the power of TB-WCS as a tool for tuberculosis drug discovery.     

Shortest Path Problem on a Network with Imprecise Edge Weight

A network with its arc lengths as imprecise number, instead of a real number, namely, interval number and triangular fuzzy number is considered here. Existing ideas on addition and comparison between two imprecise numbers of same type are introduced. To obtain a fuzzy shortest path from a source vertex to all other vertices, a common algorithm is developed which works well on both types of imprecise numbers under consideration. In the proposed algorithm, a decision-maker is to negotiate with the obtained fuzzy shortest paths according to his/her view only when the means are same but the widths are different of the obtained paths. Otherwise, a fuzzy optimal path is obtained to which the decision-maker always satisfies with different grades of satisfaction. All pairs fuzzy shortest paths can be found by repeated use of the proposed algorithm.